Genetics

Question 1

Answer 1

HYPOMELANOSIS OF ITO

Genetics: unknown

Inheritance: de novo (typically)

Clinical Features: unilateral or bilateral macular hypo- or hyperpigmented whorls, streaks and patches (sometimes following lines of Blaschko), hair and tooth anomalies are common, ocular abnormalities (strabismus, nystagmus), musculoskeletal system (growth asymmetry, syndactyly, polydactyly, clinodactyly, scoliosis), CNS abnormalities (microcephaly, seizures, ID), cardiac defects

Investigations: R/O Incontinentia pigmenti, which is genetically inherited and requires genetic counselling in future

Management: symptomatic

Question 2

Answer 2

Preauricular skin tag

Associated with:

• Goldenhar syndrome
• Treacher-Collins syndrome
• Wolf-Hirschhorn syndrome

Question 3

Answer 3

Clinodactyly of the 5th finger

Associated with:

• Trisomy 21
• Normal familial variant

Question 4

Answer 4

Macroglossia

Associated with:

• Beckwith Wiedemann syndrome
• Mucopolysaccharidosis
• Neurofibromatosis
• Glycogen storage disease - type 2
• Klippel-Trenaunay-Weber syndrome

Question 5

Answer 5

Microretrognathia

Associated with:

• Pierre Robin sequence
• Treacher-collins syndrome

Question 6

Answer 6

Encephalocele

Question 7

Answer 7

Postaxial polydactyly

Question 8

Answer 8

Bilateral clubfoot

Question 9

Answer 9

Hypospadias

Question 10

Answer 10

Fused labia with clitoromegaly

Question 11

Answer 11

Imperforate anus

Question 12

Answer 12

Amniotic band syndrome

Question 13

Happy child, wide open mouth, seizures

Answer 13

ANGELMAN SYNDROME

Genetics: UBE3A gene deletion/mutation on Ch 15

Imprinting disorder (lack of maternal contribution/uniparental disomy of paternal gene)

Clinical Features: Microcephaly, hand flapping, ADHD, atypical laughing/smiling, Seizures, Hypopigmentation (skin/eyes), smooth palms, increased sensitivity to heat, prominent mandible, wide mouth, protruding tongue, arm tremors, jerky movements

Investigations:

• Methylation testing of Chromosome 15

Monitoring

• Hyperactivity and poor sleep improves over time
• Seizures escalate around time of puberty (especially in girls)
  
  • avoid carbamazepine, vigabatrin and tiagabine

Question 14

Answer 14

ACHONDROPLASIA

Gene: FGFR3 gene, codon 380

Inheritance: behaves Autosomal Dominant

Clinical features: Frontal bossing, depressed nasal bridge, sausage fingers, disproportionate size (short extremities, large head), small chest, protruding belly, trident hand

Associations:

• Hydrocephalus (d/t foramen magnum stenosis)
• Middle ear dysfunction (40% hearing loss, frequent AOM)
• Delayed motor milestones (often not walking until 18-24mo)
• Obstructive sleep apnea
• Delayed speech + articulation difficulties
• Dental crowding
• Bowing of legs (may need surgical correction)
• Obesity

Work-up

• Skeletal radiographs (short vetebral pedicles, large calvarial bones)
• Genetic testing

Long-term

• Monitor for developmental delay, scoliosis, arthritis, hydrocephalus
• Referral to ENT, dentistriy
  *

Question 15

Answer 15

ALAGILLE SYNDROME

Genetics: JAG1, NOTCH2 mutations

Inheritance: Autosomal Dominant

Clinical Features: Butterfly vertebrae (clefting, failure of fusion), Posterior embryotoxon, Conjugated hyperbilirubin due to bile duct paucity, Peripheral pulmonary artery steonosis, renal disease, pancreatic insufficiency, growth delay, ID/GDD

Investigations:

• Radiographs: XR spine
• Ultrasound of gallbladder/HIDA
• Echocardiogram
• Genetics - sequence analysis of JAG1/NOTCH2

Monitoring

• Multidisciplinary (Genetics, GI, Nutrition, Nephro, Ophtho, Cardio)
• Ursodiol for cholestasis
• Liver transplant for ESRD
• Fat soluble vitamin supplementation
• Avoid contact sports and alcohol

Question 16

Answer 16

ATAXIA TELANGIECTASIA

Inheritance: Autosomal Recessive

Complex immunodeficiency disorder with DNA repair defect

Clinical Features: Initially normal, develop ataxia ~2-3yo [usually first 6y of life] (wheelchair bound by 15yo), oculomotor apraxia (cannot make fast eye movements), Telangiectasia (last to appear), Immunodeficiency (decreased Ig, T-cell dysfunction), Malignancy (leukemia, lymphoma), recurrent sinus/pulmonary infections can lead to bronchiectasis

Investigations:

• Elevated AFP
• Low serum IgA
• Genetic testing

Monitoring:

• Supportive
• Death in 20s

Question 17

Macroglossia, hemihypertrophy, omphalocele

Answer 17

BECKWITH WIEDEMANN SYNDROME

Inheritance: Imprinting disorder (Ch11p15); Autosomal dominant

Higher risk in IVF pregnancies

Clinical Features: Polyhydramnios, LGA baby, Macroglossia, Abdominal wall defects (omphalocele), pre-auricular ear creases/pits, renal abnormalities, hemi-hypertrophy, hyperplasia of organs, renal abnormalities, neoplasms (Wilms, adrenal carcinoma, hepatoblastoma)

Investigations: Chromosomal microarray

Monitoring:

• Hypoglycemia (infants)
• Abdo US q3mo until 8yo
• Serum AFP q3mo until 4yo
• CXR periodic (thoracic neuroblastoma)
• Renal US annually (8-16y)
• Ortho (hemihypertrophy)

Question 18

Answer 18

CHARGE SYNDROME

Genetic: CHD7 mutations

Inheritance: Autosomal Dominant

Clinical Features:

• Coloboma
• Heart defect (conotruncal, AV canal, aortic arch)
• Atresia choanae (TEF, cleft lip and palate)
• Retardation of growth (short +/- GH deficiency)
• GU anomalies (single kidney, hydronephrosis, renal hypoplasia, micropenis, hypoplastic labia, cryptorchidism)
• Ear anomalies (question mark ear)

Can have facial asymmetry due to CNVII palsy, square face with flat midface, broad nose, swallowing difficulties due to CN abnormalities.

Investigations: Genetic testing, echocardiogram, abdominal U/S

Management:

• ENT, Ophtho, Nephro/Urology, Cardiology referral

Question 19

Answer 19

CYSTIC FIBROSIS

Genetics: gene that codes for the CFTR protein (majority are ΔF508)

Inheritance: Autosomal Recessive

Mechanism: CFTR dysfunction = ↓Cl secretion and ↑Na absorption, leading to dehydrated/viscous mucus

Clinical Features (I’m CF Pancreas)

• Infertility
• Meconium ileus
• Cough
• Failure to thrive
• Pancreatic insufficiency
• Asthma (refractory)
• Nasal polyps
• Clubbing
• Rectal prolapse
• Electrolyte abnormalities (metabolic alkalosis, ↓Na, ↓Cl, ↓K)
• Atypical organisms from sputum
• Sludge (cholelithiasis/cystitis, pancreatitis, sinusitis)

Respiratory: bronchiectasis, pneumothorax, respiratory failure

Gastrointestional: DIOS, intussusception, biliary cirrhosis, hepatic steatosis, GERD, inguinal hernia, steatorrhea, fat-soluble vitamin deficiency (A, D, E, K)

Delayed puberty, hypertrophic osteoarthropathy/arthritis, amyloidosis, aquagenic palmoplantar keratoderma (skin wrinkling), hypoproteinemia

Diagnosis:

Requires clinical features OR sibling with CF OR positive NBS

AND

Elevated sweat chloride OR abnormal nasal potential difference OR identification of 2 disease-causing CF mutations

Management:

• Suppressive antibiotic therapy
• Mucociliary clearance (chest PT)
• inhaled mucolytics (DNase if >6yo)
• Bronchodilators
• Inhaled 3%NaCl
• Antiinflammatory: NSAIDs and macrolides (3x/wk)
• Nutrition: enzyme replacement, vitamin supplements, high-fat, high protein diet, MCTs added
• Insulin PRN
• Ursodiol to prevent/treat liver disease
• CFTR modulators
• Lung transplant

Question 20

Characterized by proteinuria, edema, ambiguous genitalia. What to screen for?

Answer 20

DENYS-DRASH SYNDROME

Genetics: WT1 gene mutation

Clinical Features:

• Nephropathy
• Ambiguous genitalia
• Bilateral Wilms tumours (<2yo)
• Proteinuria in infancy → nephrotic syndrome (edema) → ESRD

Question 21

Answer 21

DiGEORGE SYNDROME

Genetics: 22q11.2 microdeletion

Clinical Features:

• Cardiac abnormalities (TOF most commonly)
• Abnormal facies (malar hypoplasia, square face, mild hypertelorism, prominent ears)
• Thymic hypoplasia + immunodeficiency
• Cleft palate + velopharyngeal insufficiency
• Hypocalcemia, hypoPTH
• 22 chromosome

Learning difficulties/ID, psychiatric issues (schizophrenia), hearing loss

Investigations: serum calcium, echocardiogram, chromosomal microarray

Management:

• Referral to Audiology, Cardiology, Ophthalmology, Immunology
• Repeat calcium levels q3-6mo, TSH, PTH
• Immune function testing

Question 22

Answer 22

DUCHENNE MUSCULAR DYSTROPHY

Genetics: Dystrophin gene mutation

Inheritance: X-linked recessive

Clinical Features: Presents at 2-3yo; proximal > distal muscle weakness, lower extremities > upper extremities, Gowers sign, Calf pseudohypertrophy, Cardiomyopathy (~15yo), Fractures, Scoliosis, Impaired pulmonary function, Obstructive sleep apnea, decreased gastric motility

Investigations: ↑CK, EMG abnormal, muscle biopsy, genetic testing for dystrophin gene (molecular)

Confined to wheelchair by age 12, death in 20s

Management:

• Multidisciplinary Neuromuscular clinic: Neurology, Rehab, Cardiology, Orthopedics, Respirology, Physiotherapy, Bone health
• Steroids to try and prolong course (↑motor function, ↑pulmonary function, ↓development of cardiomyopathy, ↓scoliosis)

Question 23

Answer 23

DYSKERATOSIS CONGENITA

Inherited multisystem telomere disorder. (AD and AR)

MAJOR Features:

• Abnormal skin pigmentation
• Nail dystrophy
• Leukoplakia (usually tongue, can involve conjunctiva, anal, urethral or genital mucosa)
• Bone marrow failure

Clinical features: Some genetic types are at risk of pulmonary/hepatic fibrosis. Can have excessive tearing. 25% have LD/ID. Short stature in 15-20%

Investigations: Telomere length study. CBC to evaluate for bone marrow failure.

Management:

• Cancer predisposition (possible): solid tumours, MDS, AML
• Androgen therapy
• Bone marrow transplant

Question 24

Answer 24

FANCONI ANEMIA

Genetic: FANC genes

Inheritance: X-linked recessive (most common)

Consider on differential for any unexplained cytopenia.

MINIMIZE RADIATION EXPOSURE because of carcinogenic risk

Bone marrow failure appears within 1st decade of life.

(↓platelets, ↑MCV, ↑HgbF appear first → neutropenia → anemia)

Clinical Features:

• Skeletal (absence of radii and/or thumb abnormalities [hypoplastic, supernumerary, bifid or absent], feet or leg anomalies, congenital hip dislocation)
• Skin hyperpigmentation of trunk, neck and skin folds, CALMs, vitiligo (alone or in combo)
• Short stature +/- GH deficiency or hypothyroidism
• Dysmorphic features: microcephaly, epicanthal folds, small eyes, abnormal shzpe, size or positioning
• Males (all infertile): underdeveloped penis, undescended, atrophic or absent testes, hypospadias or phimosis
• Females: reduced fertility, malformations of ovary, uterus and ovary
• 10% ID
• IUGR/LBW

Predisposition to MDS (myelodysplasia), AML and SCC.

Investigations:

• Lymphocyte chromosomal breakage study
• Imaging: U/S abdomen, echocardiogram
• If short stature - work-up for GH deficiency
• Blood work should include: liver, thyroid, metabolic and immune system

Management:

• HSCT - only curative therapy
• Androgen therapy
• Referrals if abnormalities identified
• Multidisciplinary team including a Hematologist
• Mild-moderate CBC AbN + no transfusion = CBC q3mo + annual BMA + BMBx PRN
• Glucose levels q6mo for hyperglycemia
• TSH annually
• Solid tumour screen with physical exam annually

Question 25

Answer 25

**FETAL ALCOHOL SPECTRUM DISORDER** Clinical Features: * Microcephaly * Epicanthal folds * Short palpebral fissures * Flat midface * Short nose * Smooth philtrum * Thin upper lip * Underdeveloped jaw * ADHD * Behavioural issues

Question 26

Answer 26

**FRAGILE X** Genetics: FMR1 gene (↑CGG repeats) Inheritance: X-linked dominant Clinical features * Facial features: Elongated face, protruding ears, high arched palate * HEENT: Recurrent otitis media/sinusitis * Flat feet, hyperextensible finger joints * Macroorchidism (post-pubertal) * Hypotonia, stereotypic movements (hand flapping) * ID, ADHD * Shy, poor eye contact, social anxiety * ASD spectrum Investigations: Cytogenetic analysis, sequencing of FMR1 gene Management: * Monitor for seizures or strabismus * Support for learning: SLP, behavioural therapy, sensory interaction, OT, special education * Self-injurious behaviour - Risperidone/Quetiapine * ADHD behaviour - stimulants * Anxiety - SSRI

Question 27

Answer 27

**FRIEDREICH ATAXIA** Genetics: Chromosome 9q13, X25 gene - codes for Frataxin (GAA repeat) Inheritance: Autosomal recessive Clinical Features: * **F**oot deformity/**F**requent falls * **R**ecessive/**R**epeats (GAA) * **I**ron accumulation in mitochondria * **E**yes move (nystagmus)/**E**xtensor plantar response * **D**iabetes mellitus/**D**ysarthria * **S**coliosis/**S**taggering gait/**S**ensory loss (vibration/proprioception) Associated Diagnoses: * Cardiomyopathy * Diabetes mellitus * Kyphoscoliosis Investigations: Genetic testing, Neuroimaging of brain/spinal cord Management: * Supportive * Death ~mid-30s due to cardiac complications * Usually wheelchair bound by late teens

Question 28

Answer 28

**HEMOPHILIA A/B** Genetic: Inheritance: X-linked recessive Clinical features: bleeding, hemarthroses, muscle hematoma, ICH Investigations: * Prolonged PTT, Low Factor (VIII or IX), normal INR (usually) * Gene testing for confirmation Management * Mild (\>5 to ≤30%): DDAVP (VIII) - if effective * Moderate (1-5%) * Severe (\<1%): Prophylactic factor replacement (3X/wk for VIII and 2X/wk for IX)

Question 29

Answer 29

**HEREDITARY SPHEROCYTOSIS** Genetics: abnormalities in ankyrin (ANK1) or spectrin (SPTB) Inheritance: Autosomal dominant (primarily) Clinical features: splenomegaly, hemolytic anemia, pallor, jaundice, fatigue, exercise intolerance, hypoplastic/aplastic crises from infection Investigations: peripheral blood smear for spherocytes, osmotic fragility Management: * Folic acid to prevent deficiency and subsequent decrease in hematopoiesis * Splenectomy (ideally ≥5yo) * Vaccinate against encapsulated organisms * Penicillin prophylaxis

Question 30

Answer 30

**HYPOHIDROITIC ECTODERMAL DYSPLASIA** Genetics: EDA gene Inheritance: X-linked recessive Clinical features: * Partial/complete absence of sweat glands * Anamalous dentition * Hypotrichosis * Facial: frontal bossing, square forehead, everted lips, prominent chin, pointed ears, conical incisors Cannot regulate temperatures - develop fevers Can have immunodeficiency Investigations: molecular genetic testing Management: * Prevent overheating with cool baths and water soaks in hot environments * Dental evaluation by 2yo (for dental prostheses and implants) * Lubricating eye drops

Question 31

Answer 31

**INCONTINENTIA PIGMENTI** Genetics: IKBKG gene Inheritance: X-linked dominant Clinical features: Alopecia, Dental anomalies (conical, late dentition), Seizures, ID, Retinal neovascularization, strabismus, optic nerve atrophy, cataracts 4 stages: bullous, verrucal, pigmentary, atretic Investigations: molecular sequencing of IKBKG Management: * Surveillance for seizures and retinal detachment * Referral to Ophtho, Genetics, Dermatology (if unsure of diagnosis), Neurology * MRI Brain (if neovascularization or ataxia)

Question 32

Answer 32

**KLINEFELTER SYNDROME** Genetics: XXY Inheritance: de novo Clinical features: * Neurologic * Developmental delay * GU: microorchidism, micropenis, hypospadias * Tall stature * Gynecomastia Associated with: metabolic syndrome, insulin resistance Investigations: Karyotype Management: * Testosterone replacement therapy in adolescents (if no spontaneous puberty) * Increased risk for testicular and breast cancer

Question 33

Answer 33

**LOEYS-DIETZ SYNDROME** Genetics: TGFBR1/TGFBR2 Inheritance: Autosomal Dominant Strong predisposition for allergic triad, aggressive arterial aneurysms and pregnancy-related complications (uterine rupture) Clinical Features: * Vascular: arterial aneurysms +/- dissections (cerebral, thoracic, abdominal) * Skeletal: pectus excavatium/carinatum, scoliosis, joint laxity, arachnodactyly, instability, C-spine maformation, club feet * Facial: widely spaced eyes, strabismus, bifid uvula, craniosynostosis * Skin: velvety and translucent skin, easy bruising, dystrophic scars Investigations: Molecular genetic testing Management: * Aortic dissection at younger ages and smaller aortic diameters than Marfan * Surgical fixation of cervical spine instability to prevent spinal cord damage * Frequent monitoring with echocardiograms +/- MRA/CTA * Counsel to avoid sports, competitive and isometric exercise

Question 34

Answer 34

**MARFAN SYNDROME** Genetics: FBN1 gene (encodes fibrillin-1) Inheritance: Autosomal Dominant Clinical features: * Face: long, narrow, enophthalmos, down-slanting palpebral fissures, malar hypoplasia, micro/retrognathia, high-arched palate with dental crowding * CNS: Normal intelligence, ectopia lentis, myopia * CVS: Pectus excavatum/carinatum, aortic dilation/dissection, mitral valve prolapse * Derm: Straie * Extremities: Arachnodactyly, reduced elbow extension, positive wrist/thumb sign * Tall stature * Scoliosis * Pneumothoraxs Investigations: Molecular genetic testing, annual echo +/- CTA or MRA Management: * Beta-blockers or ARB to reduce hemodynamic stress * Avoid contact sports due to risk of aortic dilation/dissection * Avoid contact sports due to risk of aortic dilation/dissection * Multidisciplinary team: ophtho, cardio, ortho, cardiothoracic surgery

Question 35

Answer 35

**McCUNE ALBRIGHT SYNDROME** Genetics: missense mutation in GNAS1 gene Inheritance: NOT INHERITED - mutation → mosaicism Cutaneous pigmentation is usually most extensive on the side with more severe bony involvement. Clinical Features: * Fibrous dysplasia of the bone - can present with limp, pain, or fracture (base of skull and proximal femurs most common) * Café-au-lait macles * Hyperfunctional Endocrinopathies: Precocious puberty (menarche by 2-3yo, mild or subclinical hyperthyroidism, increased GH * Oversecretion of FGF23 → phosphaturia →rickets or osteomalacia Investigations: XR/CT skull for craniofacial fibrous dysplasia, labs (endo), genetic testing Management: * Bone pain - IV pamidronate or bisphosphonates * Regular vision screening * Screen for scoliosis * Calcium and PTH assessed periodically

Question 36

Answer 36

**MILLER-DIEKER PHENOTYPE LISSENCEPHALY** Genetics: Chromosome 17 (de novo deletion most common) Inheritance: Autosomal Dominant Clinical Features: Prominent forehead, midface hypoplasia, small upturned nose, low set, abnormally shaped ears, small jaw, thick upper lip Associated conditions: Seizures (\<6mo), ID/GDD, Spasticity and hypotonia, feeding difficulties, abnormal muscle stiffness Investigations: Symptomatic and chromosomal microarray

Question 37

Answer 37

**MYOTONIC DYSTROPHY** Genetics: 19q13.3 of DMPK (CTG repeat) in DM1 Inheritance: Autosomal dominant Typical pattern of weakness: facial muscles, hand intrinsic muscles, ankle dorsiflexors Clinical Features: * Congenital: hypotonia, arthrogryposis, poor feeding, respiratory failure * Childhood: cognitive/behavioural problems before 10yo, skeletal and respiratory muscle weakness, myotonia, cataracts, cardiac arrhythmias Investigations: Genetic testing, EMG/NCS if diagnostic uncertainty, CK usually only mildly elevated Management: Supportive (neuromuscular clinic, neurology, cardiology, respirology)

Question 38

Answer 38

**NEUROFIBROMATOSIS TYPE 1** Genetics: NF1 (tumour suppressor) Inheritance: Autosomal Dominant Diagnostic Criteria (≥2 of): * ≥6 CALM (≥5mm if child; ≥15mm if postpubertal) * ≥2 neurofibromas or ≥1 plexiform neurofibroma * Axillary or inguinal freckling * Optic glioma (\<10yo) * ≥2 Lisch nodules (\<20 years of age) * Tibial pseudoarthrosis or sphenoid dysplasia * 1st degree relative with NF1 Associated Conditions: Seizures, Scoliosis, Tumours (pheochromocytomas, gliomas, juvenile myelomonocytic leukemia, breast cancer) Investigations: NF1 molecular genetic testing; Imaging - MRI Management: * Annual physical examination with routine BP and scoliosis monitoring * Annual ophtho assessment * Monitoring if approaching criteria (most meet it by 8yo) * Normal intelligence (may have LD) * MRI if clinically suspecting internal tumours * Routine tumour surveillance and management * Prenatal preimplantation genetic diagnosis can be considered

Question 39

Answer 39

**NEUROFIBROMATOSIS TYPE 2** Genetics: NF2 gene (tumour suppressor) Inheritance: Autosomal Dominant (2 hit phenomenon) Clinical features: bilateral vestibular schwannomas, meningioma, subscapular cataracts, plexiform schwannomas, neurofibromas Investigations: Molecular genetic diagnosis Management: Ophthalmology, MRI of brain (annually after 10yo), audiology, brainstem-evoked potentials

Question 40

Answer 40

**NOONAN SYNDROME** Genetics: multiple genes involved (50% PTPN11) Inheritance: Autosomal Dominant Clinical Features: hypertelorism, ptosis, short/webbed neck, low-set, posteriorly rotated ears, short stature coarse facial features, curly/wooly hair, low posterior hairline, wide forehead, neck skin webbing, micrognathia, widely spaced nipples, pectus carinatum, lymphedema, chylothorax, cryptorchidism Associated syndromes: Pulmonary Valve Stenosis, Hypertrophic Cardiomyopathy, Scoliosis, JMML, ALL, neuroblastoma, brain tumours, amegakaryocytic thrombocytopenia, hypocellular marrow causing pancytopenia Investigations: genetic testing, echocardiogram, renal U/S, audiology, vision assessment, coag screen during childhood Management: * Feeding assessment * Growth and neurodevelopmental monitoring * Monitor for seizures, craniosynostosis, hydrocephalus and Chiari malformation * Scoliosis monitoring

Question 41

Answer 41

**PRADER-WILLI SYNDROME** Genetics: paternal chromsome 15 Inheritance: imprinting/maternal UPD Clinical Features: severe hypotonia, feeding difficulties, excessive eating/morbid obesity, delayed motor/speech, cognitive impairment, temper tantrums/stubborn/manipulative, OCD, hypogonadism (male/female): incomplete pubert/infertility, strabismus, scoliosis Investigations: DNA methylation studies on chromosome 15 Management: * Infancy: feeding support, physiotherapy, possible surgery for cryptorchidism, screen for strabismus * Childhood: strict monitoring of food intake/BMI to prevent T2DM, GH therapy, sleep disturbances, educational/behavioural plans; *Topiramate may help skin picking*, screen for strabismus, Ca/Vit D to prevent osteoporosis * Adolescence: preplacement of sex hormones at puberty, SSRIs

Question 42

Answer 42

**RETT SYNDROME** Genetics: MECP2 Inheritance: typically de novo; can be X-linked Dominant Clinical Features: microcephaly, seizures (by 3yo), usually meet developmental milestones for first 6-9 months before rapidly losing milestones (coordination, speech and use of hands) - never regain the skills they've lost, autonomic difficulties - cold hands and feet Diagnostic criteria (need all for clinical diagnosis) * Pattern of development, regression then recovery or stabilization * Partial or complete loss of purposeful hand skills such as grasping with fingers, reaching for things or touching things on purpose (between 2-3yo) * Partial or complete loss of spoken language * Repetitive hand movements, such as hand-wringing, washing, squeezing, clapping or rubbing * Gait abnormalities, including walking on toes or with an unsteady, wide-based, stiff-legged gait Investigations: Management: Symptomatic * Multidisciplinary team: PT/OT/SLP * Nutrition therapy * Splints/braces for scoliosis and hand movements * Medications for respiratory difficulties, seizures and/or long QT syndrome

Question 43

Answer 43

**RUSSELL SILVER SYNDROME** Genetics: abnormal methylation of 11p15.5 and maternal UPD on chromsome 7 Inheritance: mostly de novo, AD/AR (depending on familial type) Clinical Features: postnatal growth restriction (normal HC), failure to thrive (but maintenance of normal head growth), feeding difficulties, triangular facies with **prominent forehead** and small, pointed chin and **clinodactyly**. Downturned corners of mouth. Males can have cryptorchidism and micropenis. **Recurrent hypoglycemia** can occur. speech delay, GDD/ID, LD. **CALMs.** Investigations: methylation analysis, array for UPD 7, deletion/duplication studies Management: * surveillance of growth, hypoglycemia and speech * Multidisciplinary team (including urology, endocrinology and GI when appropriate)

Question 44

4-month-old female infant with FTT, history of loose, greasy stools and pallor on physical examination. Laboratory investigations reveal anemia, neutropenia and thrombocytopenia. What is the most likely diagnosis?

Answer 44

**SHWACHMAN DIAMOND SYNDROME** Genetics: SBDS gene Inheritance: Autosomal Recessive Clinical Features: Pancreatic insufficiency (FTT, steatorrhea), Cytopenias (primarily neutropenia), Skeletal Abnormalities (due to metaphyseal dysostosis), recurrrent pyogenic infections Associated conditions: Myelodysplastic syndrome, AML Investigations: neutropenia\>anemia\>thrombocytopenia, abnormal fecal fat and elastase, low serum trypsinogen, normal sweat test (differentiates from CF), mutations in SBDS gene on chromosome 7 XR - widened, irregular metaphyses, thickened and irregular growth plates AXR - hypodense appearance of pancreas due to fatty replacement Management * exocrine pancreatic insufficiency - treated with pancreatic enzyme replacement therapy * fat-soluble vitamin replacement * Monitor cytopenias and for leukemic transformation * early dental evaluation and follow-up for enamel defects

Question 45

Answer 45

**SMITH-LEMLI-OPTIZ SYNDROME** Genetics: DHCR7 gene Inheritance: Autosomal Recessive Clinical Features: microcephaly, ID/LD, autism features, syndactyly or polydactyly. Cardiac, pulmonary, renal and GI/GU malformations are common. Hypotonic infants with feeding difficulties. Investigations: serum cholesterol and precursors (adrenal insufficiency screen), sequence analysis of DHCR7 gene Management: * Cholesterol supplementation (egg yolk) * HMG-CoA reductase inhibition to prevent toxic precursors proximal to enzymatic block * often need G-tubes/dietitian * Avoid sun and antipsychotics * screen for cholestatic and noncholestatic liver disease

Question 46

Answer 46

**SOTOS SYNDROME** (Cerebral gigantism) Genetics: NSD1 Inheritance: typically de novo; Autosomal Dominant \*\*not due to endoc Clinical Features: distinct facial features (sparse frontotemporal hair, downslanting palpebral fissures, malar flushing, long thin face), LD, **overgrowth** (height and HC), autism features, advanced bone age, cardiac anomalies, joint hyperlaxity, scoliosis, seizures Investigations: molecular genetic testing Management: referrals based on symptoms

Question 47

Answer 47

**TREACHER COLLINS SYNDROME** Genetics: TCOF1, POLR1C Inheritance: Autosomal Dominant, Autosomal Recessive Clinical features: Bilateral downslating palpebral fissures, underdeveloped lower jaw/zygomatic bone, retracted tongue, micrognathia, dental issues, external ear malformation (absent, small, malformed, canals atretic/stenotic/rotated), significant feeding/breathing issues, conductive hearing loss, bilateral choanal atresia, normal intellect Investigations: Molecular genetic testing Management: Multidisciplinary; craniofacial reconstruction required, audiology, SLP, may require tracheostomy

Question 48

Answer 48

**TRISOMY 13 - PATAU SYNDROME** Genetics: Trisomy 13 Inheritance: de novo 50% die within 1st month; 70% by 1st year Clinical features: midline defects, holoprosencephaly, seizures, **cutis aplasia,** omphalocele, **cleft lip/palate,** clenched fists, **polydactyly,** failure to thrive, CHD, renal anomalies Investigations: Karyotype, Imaging (EEG, Brain MRI, Echocardiogram, RBUS), Audiology Management: Supportive

Question 49

Answer 49

**TRISOMY 18 - EDWARD'S SYNDROME** Genetics: Trisomy 18 Inheritance: usually de novo 50% die within 1st week; 90% die within 1st year Clinical Features: microcephaly, hypertonia, CHD (VSD/ASD, PDA), cryptorchidism, **clenched fists** (overlapping digits 2/3 and 5/4), **rocker-bottom feet**, IUGR, renal anomalies (horseshoe, polycystic, hydronephrosis) Investigations: Karyotype, Imaging (echocardiogram, abdo U/S) Management: Supportive

Question 50

Answer 50

**TRISOMY 21 - DOWN SYNDROME** Genetics: Trisomy 21 Inheritance: de novo; balanced translocation Clinical Features: facial features (epicanthal folds, upslanting palpebral fissures, flat nasal bridge), Brushfield spots in iris, hypotonia, conotruncal defects CHD (AVSD), GI malformations (duodenal atresia, TEF, Hirschsprung, imperforage anus), celiac disease, 5th finger clinodactyly, single palmar crease, sandal gap toes Associated Conditions: 10% develop transient myeloproliferative disorder; 1% lifetime risk of leukemia, OSA (\>50%), obesity, hearing loss Investigations: karyotype, CBC, TSH, Echocardiogram, XR of C-spine if symptomatic (neck pain, head tilt, gait instability), Abdo U/S, UGI/small bowel follow-through if concerned about duodenal atresia, Polysomnography by 4yo Management: * _1mo-1y:_ TSH at 6+12mo, * _1-5y:_ Growth, Development, examine TMs, audiogram q6mo until 3y or until pure tone audiogram obtained. Sleep study by 4yo. Annual ophtho, Cspine XR btwn 3-5y, PT/OT/SLP PRN * Trampoline/contact sport safety, if cardiac/pulmonary disease, 23-valent pneumococcal vaccine \>2yo * _5-13y_: Growth, Development, annual audiology, q2y ophtho, screen dry skin, gyne * _13-21y:_ annual audiology, q3y ophtho, screen dry skin, sexuality * _All years:_ screen myopathy, OSA & sx of celiac disease, annual CBC/TSH (6+12mo in 1st year of life), discuss complementary/alternative tx, C-spine positioning,

Question 51

Answer 51

**TUBEROUS SCLEROSIS COMPLEX (TSC)** Genetics: TSC1 / TSC2 Inheritance: Autosomal Dominant Clinical Features (ASHLEAF): confetti skin lesions, ungual fibromas, dental pits, subependymal giant cell astrocytomas (SEGAs), lymphangioleiomyomatosis (LAM - in females), retinal hamartomas; * **A**shleaf spots (\>3) * **S**hagreen patches * **H**eart rhabdomyosarcoma * **L**ung hamartomas * **E**pilepsy from cortical tubers * **A**ngiomyolipoma in kidney * **F**acial angiofibroma Associated Conditions: Autism, ADHD, ID, disruptive behaviours, anxiety, depression; Infantile Spasms Investigations: TSC1/TSC2 molecular genetic testing, Brain MRI, EEG, Echocardiogram, RBUS, Ophthalmologic assessment Management: * mTOR inhibitors help; * Vigabatrin works for seizures * Surgery as needed (neurosx, cardiac, renal) * Brain MRI + Echo Q1-3yo * EEG if Sz * Abdo MRI is abdo findings * Sx screen for LAM every visit ( CT if suspected → PFTs if positive) * Annual skin exam * Annual ophtho exam if findings * Avoid smoking, estrogen use

Question 52

Answer 52

**TURNER SYNDROME** Genetics: XO Inheritance: de novo Clinical Features: Webbed neck, redundant nuchal skin, low posterior hairline, shield chest with wide-spaced nipples, left-sided CHD (bicuspid aortic valve, coarctation), congenital lymphedema (hands and feet), dysplastic nails, skeletal abnormalities (short 4th and 5th metacarpals, cubitus valgus, scoliosis, congenital hip dislocation), short stature, renal abnormalities (horseshoe kidney, duplex collecting system), streaked ovaries Associated Conditions: Delayed puberty, Infertility, Autoimmune disorders (Diabetes, hypothyroidism, celiac disease, IBD) Investigations: Karyotype, TSH, FSH/LH, RBUS, Echocardiogram, Audiology for nonsyndromic hearing loss Management: Referral to Ophthalmology (strabismus, hyperopia), growth hormone for short stature, estrogen therapy if no spontaneous puberty by 13yo, screening for autoimmune disorders

Question 53

What are the conditions associated with VACTERL association?

Answer 53

**V**ertebral defects **A**nal atresia **C**ardiac defects **T**racheoesophageal fistula **E**sophageal atresia **R**enal anomalies **L**imb abnormalities

Question 54

Answer 54

**WAARDENBURG SYNDROME** Genetics: PAX3 (1+3), 2: MITF, SNAI2, 4: EDN3, EDNRB, SOX10 Inheritance: Autosomal Dominant (usually) Clinical Features: * Type 1: median white forelock, depigmented patches (vitiligo), SNHL, heterochromia, unibrow (synophrys), premature graying, hypertelorism * Type 2: Similar to type 1 with no hypertelorism and more SNHL * Type 3: Similar to type 1 with limb abnormalities * Type 4: ALWAYS have Hirschsprung disease Investigations: Molecular studies Management: Audiology

Question 55

Answer 55

**WAGR SYNDROME** Genetics: chromosomal 11 deletion Inheritance: typically de novo Clinical Features: * **W**ilms tumour * **A**niridia (or cataracts, glaucoma, nystagmus) * **G**enitourinary anomalies (hypospadias, cryptorchidism, streak ovaries, bicornuate uterus) * **R**etardation - Intellectual disability Associated Conditions: Obesity, ADHD, OCD, autism Investigations: Chromosomal microarray, AFP Management: Supportive care, routine US surveillance for Wilms tumour until 9yo; Ophthalmologic evaluation q6m when \<8yo

Question 56

Answer 56

**WILLIAMS SYNDROME** Genetics: Deletion of Chromsome 7 Inheritance: typically de novo (transmission Autosomal Dominant) Clinical Features: **"elfin facies"** (broad forehead with bitemporal narrowing, periorbital fullness, malar hypoplasia, long philtrum, full lips with side mouth), prominent earlobes, stellate iris, f**riendly "cocktail party personality"**, ID, **supravalvular aortic stenosis** +/- coarctation, pulmonary artery stenosis, renal artery stenosis, hernias (umbilical, inguinal), rectal prolapse, hypothyroidism, hypercalcemia, FTT Investigations: chromosomal microarray, ELN molecular genetic testing, serum/urine calcium, thyroid function testing, RBUS, Echocardiogram, Audiology Management: Ophthomology referral, monitor for hypercalciuria, aggressive constipation management to minimize rectal prolapse, supportive care

Question 57

Answer 57

**WILSON DISEASE** Genetics: AT7B gene Inheritance: Autosomal recessive Copper accumulates in liver first, then other tissues (basal ganglia, cornea, kidney) Clinical Features: acute hepatitis then in 2nd/3rd decades of life → basal ganglia involvement (dystonia, fine motor problems, gait disturbances), psychiatric symptoms (depressive, impulsive or psychotic features), Kayser-Fleischer ring Associated Conditions: Coombs negative hemolytic anemia, proximal tubular deficit, cardiac problems, osteopenia Investigations: Elevated liver enzymes (classically AST\>ALT and bilirubin \> ALK), **↓ceruloplasmin,** ↑urine copper, liver biopsy, genetic testing if diagnosis is questionable and to screen siblings Management: * Copper chelating agents: penicillamine or trientine dihydrochloride * Zinc supplementation interferes with copper absorption (can be monotherapy after chelation or in asymptomatic individuals) * Avoid foods with high copper content * Transplant for those with fulminant liver failure or severe liver disease failing medical therapy

Question 58

Eczema, thrombocytopenia, immunodeficiency?

Answer 58

**WISKOTT-ALDRICH SYNDROME** Genetics: mutation in WASP gene Inheritance: X-linked recessive Clinical Features: **eczema, thrombocytopenia, immunodeficiency**, Recurrent infections (sinopulmonary) * Mnemonic = WATER (Wiskott, Aldrich, Thrombocytopenia, Eczema, Recurrent sinopulmonary infections) Associated Conditions: lymphoreticular malignancies Investigations: CBC (eosinophilia, microthrombocytopenia), elevated IgE, poor vaccine responses Management: Immunoglobulin replacement, HSCT or gene therapy, splenectomy for thrombocytopenia (but increases infection risk)

Question 59

Answer 59

**HYPER IgE SYNDROME - JOB SYNDROME** Genetics: STAT3 gene Inheritance: Autosomal Dominant Clinical Features: Eczema, cold abscesses (usually *S aureus*), recurrent pneumonias with pneumatoceles (usually *S aureus*), mucocutaneous candidiasis, cardiofacial dysmorphisms (coarse facies, wide nose, deep-set eyes), skeletal abnormalities (short stature, retained teeth, frequent bone fractures) Investigations: CBC/diff, lymphocyte subsets for evaluation of T cells, Immunoglobulin levels, lymphocyte proliferation, vaccine titers, R/O ataxia telangiectasia and 22q11.2 deletion; **↑IgE, eosinophilia, STAT3 sequencing** Management: immune therapies (depending on degree of immunodeficiency) - prophylactic antibiotics, immunoglobulin replacement therapy, skin emollients, surgical intervention for drainage of abscesses

Question 60

Answer 60

**ALPORT SYNDROME** Genetics: COL4A5 gene (80%) Inheritance: X-linked recessive (80%) Clinical Features: progressive SNHL by early adulthood, lens and retina anomalies (anterior lenticonus), esophageal/tracheobronchial leimyomas; presents with episodic gross hematuria concurrent with an illness, progressive kidney disease (more common in males) Investigations: UA for hematuria/proteinuria, renal biopsy (focal glomerulosclerosis, tubular atrophy, interstitial fibrosis, interstitial foal cells), Audiology Management: proteinuric control with ACEi/ARBs, supportive for ESRD (late adolescence for males, later for females), renal transplant

Question 61

Answer 61

**STURGE-WEBER SYNDROME** Genetics: GNAQ gene Inheritance: de novo (mosaicism) Clinical Features: unilateral capillary malformation of the face (port-wine birthmark) with ipsilateral brain involvement (leptomeninges), as well as abnormal blood vessels of eyes, ID/GDD, seizures (contralateral side) with prolonged postictal deficits, hemiparesis STURGE = Stain, Tram track calcifications, Unilateral, Retardation, Glaucoma, Epilepsy Associated conditions: Glaucoma (ipsilateral) Investigations: Brain MRI, ophthalmologic evaluation Management: seizure control, relief of headaches, prevention of stroke-like episodes, monitoring for glaucoma and laser therapy for cutanaeous capillary malformations, monitor for psychological trauma (bullying)

Question 62

Answer 62

**MUSCULAR DYSGENESIS - PROTEUS SYNDROME** Genetics: AKT1 gene Inheritance: de novo (mosaicism) Clinical Features: overgrowth of ectodermal/mesodermal tissues, asymmetric overgrowth of extremities, verrucous cutaneous lesions (usually on soles of feet), angiomas of various types, thickening of bones, excessive growth of muscles without weakness, facies (long, narrow head, downslanting palpebral fissures, ptosis, depressed nasal bridge, wide nares) Associated Conditions: Seizures, ID, visual loss, VTEs (DVT/PE) Management: Symptomatic

Question 63

Answer 63

**CONGENITAL CONTRACTURAL ARACHNODACTYLY - BEALS SYNDROME** Genetics: FBN2 gene Inheritance: Autosomal Dominant Clinical Features: tall and slender, phenotypically resembling Marfan syndrome with **congenital contractures** (usually elbows, knees, hips, fingers and ankles), **crumpled looking ears**, kyphoscoliosis Investigations: molecular genetic testing, echocardiogram Management: symptomatic

Question 64

Answer 64

**CROUZON SYNDROME** Genetics: FGFR2 gene mutation Inheritance: Autosomal Dominant Clinical Features: **craniosynostosis**, facial dysmorphism (prominent forehead, hypertelorism, proptosis, midface hypoplasia, cleft lip/palate, beaked nose, prognathism), normal intelligence Associated Conditions: Dental issues, Hearing loss, Hydrocephalus Differential Diagnosis: Apert syndrome, Pfeiffer syndrome Investigations: Molecular genetic testing, XR spine (r/o vertebral anomalies) CT/MRI Head for surgical correction and monitor for hydrocephalus Management: Craniofacial surgery multidisciplinary team, hydrocephalus surveillance

Question 65

Answer 65

**EHLERS DANLOS SYNDROME** Genetics: multiple types - collagen defect Inheritance: AD (classic), AR (few other forms) Clinical Features: Hypermobility, MVP, aortic root dilation, hernias, rectal prolapse, skin hyperextensibility, atrophic scars, smooth skin, molluscoid pseudotumours, subcutaneous spheroids, easy bruising, easy dislocations/subluxations, cramping, fatigue, chronic pain Investigations: molecular genetic testing, echocardiogram (aortic dilation, MVP) Management: physiotherapy, non-weight bearing exercises promote strength (avoid those that strain joints), pregnancy shoudl be monitored closely, vascular type - monitoring for life-threatening complications

Question 66

Answer 66

**OSTEOGENESIS IMPERFECTA** Genetics: COL1A1/COL1A2 Inheritance: Autosomal Dominant Clinical Features: Triangular-shaped face, large skull, normal intelligence, hearing loss, easy bruising, Radiographic findings (wormian bones, 'codfish' vertebrae, osteopenia, fractures) Types * I: nondeforming OI with blue sclerae * II: perinatally lethal OI * III: progressively deforming OI * IV: common variable OI with normal sclerae Investigations: Molecular genetic testing, radiographs Management: Bisphosphonate infusions to decrease bone resorption, Growth hormone to increase linear growth, multidisciplinary care including involvement from ortho, rehab, dentistry, ENT

Question 67

Answer 67

**PIERRE ROBIN SEQUENCE** (isolated) Genetics: SOX9 Inheritance: de novo Clinical Features: micrognathia, glossoptosis, airway obstruction, cleft palate or high arched palate Associated conditions: If myopia+skeletal abnormalities - consider Stickler syndrome (and also check for DiGeorge) Management: Prone positioning so tongue falls forward to relieve respiratory obstruction. Surgical procedures (tracheostomy, mandibular distraction) to facilitate oral feedings, enhance respiration

Question 68

Answer 68

**CRANIOFACIAL MICROSOMIA - GOLDENHAR SYNDROME** Genetics: unknown Inheritance: de novo Clinical Features: Facial asymmetry, microtia, preauricular tags, microphthalmia, cleft lip/palate, **epibulbar dermoid**, vertebral anomalies, CHD Investigations: Clinical diagnosis Management: Craniofacial multidisiplinary team, ophthalmology

Question 69

What genetic disorder is associated with an increased risk of sarcoma, breast cancer, leukemias and adrenal tumours?

Answer 69

**LI-FRAUMENI SYNDROME** Genetics: CHEK2, TP53 Inheritance: Autosomal Dominant Associated Conditions: soft-tissue sarcomas, osteosarcoma, premenopausal breast cancer, brain tumors, leukemias, adrenocortical carcinoma Investigations: molecular genetic testing Management: * Breast cancer monitoring with annual MRI and biannual clinical breast examination for patients \>20yo * Annual pelvic examination and mammography \>40yo * Prophylactic mastectomy is offered to those with TP53 mutations * Routine colonoscopy q2-3y for those \>25yo * Avoid radiation and carcinogen (tobacco, sun, alcohol) exposure

Question 70

Answer 70

**CRI-DU-CHAT SYNDROME** Genetics: Chromosome 5 deletion Inheritance: de novo Clinical Features: shrill, high-pitched cry (in first few weeks of life), hypertelorism, low-set ears, wide and flat nasal bridge, epicanthic folds, microcephaly with protruding metopic suture, micrognathia, CHD, cleft palate or high-arched palate, hypotonia, short stature, ID Investigations: chromosomal microarray, echocardiogram if concern for CHD Management: Supportive

Question 71

Answer 71

**WOLF-HIRSCHHORN SYNDROME** Genetics: deletion of short arm of chromosome 4 Inheritance: de novo (typically Clinical Features: **"greek warrior helmet" appearance** (hypertelorism, high forehead with prominent glabella, broad/flat nasal bridge), microcephaly, cleft lip/palate, CHD, GU malformations, hypotonia, structural brain anomalies Associated Conditions: Hepatic adenomas, Intellectual Disability, Seizures, CVID, IgA deficiency Investigations: chromosomal microarray, IgA levels, CBC, renal function testing, echocardiogram, MRI, EEG as needed Management: Supportive with multidisciplinary team

Question 72

Answer 72

**CHARCOT-MARIE TOOTH DISEASE** Genetics: PMP22 gene duplication Inheritance: Autosomal dominant Clinical Features: Slowly progressive, symmetric distal weakness (foot drop causing frequent tripping), atrophy of distal muscles, contractures of hands and feet due to weak distal muscles, pes cavus (high-arched feet), hammer toes, gradual loss of distal sensation Investigations: EMG/NCS, molecular genetic testing Management: Supportive care (stretching, orthotics), may require orthopedic surgery, no gene therapy available at present time

Question 73

Motor delays, gout, nephrolithasis, spasticity, dystonia, self-injurious behaviours

Answer 73

Lesch-Nyhan Syndrome * X-linked recessive * Gene = HPRT (leads to elevated uric acid) Presentation: * gout, nephrolithiasis * developmental delay (motor then GDD) * movement (choreoathetosis, spasticity, dystonia) * self injury (ie. biting fingers and mouth) * megaloblastic anemia

Question 74

Answer 74

Triphalangeal Thumbs **_Diamond-Blackfan Anemia:_** * Autosomal dominant * Doesn't present with pancytopenia * Just profound anemia (macrocytic anemia with no retics) * Presents in infancy (by age 2-6 months) * Findings: * Growth delay * Craniofacial abnormalities (hypertelorism) * Thumb abnormalities * Treatment: * Steroids (80% respond) * If refractory then pRBC transfusions every 1-2 months with chelation for iron * Can do BM transplant only if HLA matched sibling donor (otherwise survival much lower)

Question 75

Answer 75

Bifid thumbs/ Hypoplastic thumbs **_Fanconi anemia (“congenital aplastic anemia”)_** * Inherited autosomal recessive inheritance * Typically have bone marrow failure by age 5-10 * Present usually at school age * Findings: * Café au lait spots * Short stature * Abnormal thumbs and radii * Microcephaly * Renal abnormalities * Cardiac defects * Pancytopenia with macrocytic anemia * Treatment: * BM transplant * Androgen therapy * Higher risk of leukemia, MDS, squamous cell carcinoma, head/neck cancers

Question 76

What is uniparental disomy? Name a syndrome that it is inherited in this manner?

Answer 76

1. when a person gets both chromosomes (or parts of chromosomes) in the pair from the same parents, instead of getting one form each parent 2. Prader Willi and Angelman (chromosome 15q11) PWS: think Trump - small balls, small hands, intellectual disability and obesity from hyperphagia - mom's part is silenced and the part you're meant to get from your dad just isn't there (mom silences (Melania), dad missing (Donald))

Question 77

You diagnose a child with CF based on an abnormal sweat chloride. The reason for doing DNA testing is: a. confirm diagnosis b. rule out whether the parents are carriers c. to diagnose her cousin who is failing to thrive with CF d. to give the parents some idea about prognosis e. so that antenatal testing can be done on subsequent pregnancies

Answer 77

d. to give the parents some idea about prognosis

Question 78

The sister of a patient with cystic fibrosis is 6 weeks pregnant and wants to know if her unborn child has cystic fibrosis. What do you suggest: a) wait until 16 weeks gestation and then perform amniocentesis b) perform chorionic villus sampling and genetic testing now c) refer the parents for genetic testing d) perform a sweat test on the mother e) you cannot accurately diagnose cystic fibrosis until after the child is born

Answer 78

c) refer the parents for genetic testing - 50% chance that the sib is a carrier (assuming she would know if she actually had CF, the chance that she's a carrier is actually 2/3) - amnio or CVS not recommended unless high risk (mutations in both parents)

Question 79

Parents of a child with unilateral cleft palate come in for advice regarding next pregnancy. You advise that: a. There is no recurrence risk b. 4% recurrence risk c. 25% of offspring will be affected

Answer 79

b. 4% recurrence risk

Question 80

Obese parents adopt a 3 month child. What is true regarding the child’s risk of obesity: a. if biologic parents are thin then child is unlikely to be obese b. even if biologic parents are thin, the child is likely to be obese c. obesity is more common in upper socioeconomic groups d. if child is obese at 1 year then there is a 90% chance of obesity as an adult

Answer 80

a. if biologic parents are thin then child is unlikely to be obese

Question 81

A child has multiple ash leaf spots, and seizures. The mother is pregnant and wants to know whether or not her unborn child will have the same problems. What do you tell her about the risks to the fetus? a) 50% if female b) 50% if male c) 50% regardless of gender d) 25% regardless of gender e) the recurrence risk is minimal

Answer 81

e) the recurrence risk is minimal TS: AD inheritance but 2/3 sporadic - if parents are unaffected the risk of another child having TS is low but still higher than the general population because of the chance of germ line mosaicism

Question 82

Inheritance pattern of ectopic thyroid: a) autosomal recessive b) autosomal dominant c) sporadic d) X-linked recessive e) X-linked dominant

Answer 82

c) sporadic (thyroid agencies including ectopic thyroid is usually sporadic, 2% will have family history)

Question 83

You are seeing a pregnant woman during her first. Her father has hemophilia. Regarding the risk of her transmitting the disorder to her own children you tell her: A. None will have it b. 50% of her sons will have it and all of her daughters will be carriers c. 50% of her sons will have it and 50% of her daughters will be carriers

Answer 83

c. 50% of her sons will have it and 50% of her daughters will be carriers X-linked disorder

Question 84

Which of the following has AD inheritance? a. Tuberous Sclerosis b. Fragile X c. CF d. Hereditary Spherocytosis

Answer 84

ANSWER: a. Tuberous Sclerosis, though 2/3 sporadic b. Fragile X - X-linked dominant, FMR1 mutation c. CF - autosomal recessive d. Hereditary Spherocytosis - 75% autosomal dominant, 25% autosomal recessive

Question 85

Which has autosomal dominant inheritance? a. Congenital adrenal hyperplasia b. PKU c. Beta-thalassemia d. Hereditary spherocytosis

Answer 85

ANSWER: d. Hereditary spherocytosis - 75% autosomal dominant, 25% autosomal recessive a. Congenital adrenal hyperplasia - autosomal recessive b. PKU - autosomal recessive c. Beta-thalassemia - usually autosomal recessive; rarely can be AD

Question 86

Teenager presents with large armspan, suspect Marfans Syndrome. What is the mode of inheritance? a. Autosomal Dominant b. Autosomal Recessive c. X linked d. Sporadic

Answer 86

a. Autosomal Dominant FBN1 mutation 25% de novo mutations

Question 87

Newborn presents with the following lab values pH 7.1; HCO3 decreased, normal sodium/potassium, Elevated lactate, ammonia and neutropenia. Diagnosis: a) galactosemia b) MCAD c) methamelonic acidemia d) urea cycle defect

Answer 87

c) methylmalonic acidemia - organic acidemia (metabolic acidosis, high ammonia, neutropenia caused from BM suppression that happens with metabolic acidosis) - dx: urine organic acids -issue: unable to metabolize methylmalonic acid which is made in the breakdown of amino acids and some fatty acids - tx: low protein diet

Question 88

What broad category of diseases do you think of in an infant with vomiting, lethargy, poor feeding and seizures but who is afebrile and has a normal WBC?

Answer 88

inborn error of metabolism

Question 89

10 day old baby with failure to thrive, jaundice, hepatomegaly, blood culture positive for E.Coli. a. What underlying disorder may the child have? b. What test can you do to confirm this diagnosis ?

Answer 89

a. What underlying disorder may the child have? Galactosemia (see above). b. What test can you do to confirm this diagnosis ? ● Erythrocyte galactose-1-phosphate uridyltransferase (GALT) activity. ● DNA testing for mutations in GALT gene - presents 4-7 days of life (after lactose has been introduced in diet - i.e. breast or bottle feeding established) - also get ketonuria

Question 90

Child presents with an ammonium level in the 400-range. What 3 things would you do in your management?

Answer 90

1. IV rehydration, including dextrose (stop protein catabolism) 2. remove ammonia (dialysis or meds - sodium phenyacetate and sodium benzoate, arginine) 3. confirm with repeat specimen 4. additional testing: serum amino acids, urine organic acids, liver function and transaminases (can have liver failure, lights)

Question 91

What are 3 symptoms of hyperammonemia?

Answer 91

lethargy, vomiting, cerebral edema, coma - encephalopathy

Question 92

You are working in an emergency department, and a 5-month-old baby presents with a history of poor intake and occasional vomiting over the past 24 hours. You find that his glucose is 2.8. The remainder of his bloodwork is unremarkable. He has no ketones present on urinalysis. List 2 diagnoses on your differential.

Answer 92

1. hyperinsulinemia 2. fatty acid oxidation defect (fatty acids have a ketone on the end - with FAO defects, you can't cut that ketone off so you have high fatty acids, but no ketones) Hypoketotic hypoglycemia - if your sugar is low, your body should make ketones as an alternate fuel no ketones = high insulin, fatty acid oxidation defect

Question 93

3 week old with previous e coli sepsis and persistent jaundice. What is the likely problem? a. Increased osmotic fragility b. RBC galactose phosphate uradyl transferase deficiency c. RBC glu – 1 – phosphate dehydrogenase deficiency

Answer 93

b. RBC galactose phosphate uradyl transferase deficiency Galactosemia

Question 94

3-day-old infant with lethargy, vomiting, hypotonia and progressively worsening level of consciousness and coma. There is subtle evidence of intracranial hypertension. He has a respiratory alkalosis. Most likely: a. encephalitis b. urea cycle defect c. maple syrup urine disease d. phenylketonuria e. Leigh syndrome

Answer 94

b. urea cycle defect amino acids--\> ammonia and organic acids ammonia (BAD)--\> urea cycle --\> urea (pee it out) MSUD: defect in enzyme that breaks down some amino acids (so you have no ammonia being made) Leigh disease: subacute necrotizing encephalomyelopathy

Question 95

You are called because an infant's PKU screen is positive. Your next step is: a. order a quantitative urine Phenylalanine level b. order a quantitative blood Phenylalanine level c. repeat the screen d. order a urinary phenylketone level

Answer 95

b. order a quantitative blood Phenylalanine level

Question 96

The child of a father with phenylketonuria will have which of the following: a) no problems b) developmental delay c) multiple congenital anomalies d) microcephaly e) IUGR

Answer 96

a) no problems inheritance AR - would expect child to be a carrier, but would only be affected if mother also a carrier signs PKU: MR, growth retardation, fair skin, eczema Maternal PKU not treated in pregnancy causes microcephaly, IUGR, MR, congenital heart defects

Question 97

6 month old with hx of dev delay is brought in to ER and needs resusc. Is now stable. What would you need to help make diagnosis: a. CT scan b. Lactate, carnitine, ammonia c. Serum organic acids d. Urine amino acids

Answer 97

b. Lactate, carnitine, ammonia Shock - think organic acidemia

Question 98

Child with poor feeding, vomiting, lethargy, seizures, afebrile. Ammonia and gas normal. What do you suspect?

Answer 98

amino acidopathy or galactosemia

Question 99

In a patient with MCAD deficiency what would be the most likely laboratory finding: a) respiratory alkalosis b) nonketotic hypoglycemia c) increased urine/plasma ketone level d) increased plasma carnitine level e) normal transaminases

Answer 99

b) nonketotic hypoglycemia - hypoketotic hypoglycemia, no acidosis, low urinary ketones - illness triggered by prolonged fasting (cannot mobilize fat stores)

Question 100

Abetalipoproteinemia causes all EXCEPT: a) ataxia b) hyperlipidemia c) acanthocytosis d) retinitis pigmentosa e) diarrhea and FTT

Answer 100

b) hyperlipidemia - hereditary inability to synthesize lipoproteins -have very low cholesterol and triglycerides (all the fats get stuck in the gut wall) - lack of fat soluble vitamins (no vit E - spinocerebellar degeneration, no vit A - night blindness)

Question 101

14 mos male, FTT, vomiting, met acidosis, pH 7.31, bicarb 14, K 3.5, Na140, Cl 118, urine pH 6.3 a distal RTA b Bartter c organic acidopathy d nutrit. Deprivation

Answer 101

a. distal RTA - hyperchloremic non anion gap metabolic acidosis - distal RTA - high urine pH Bartter - alkalosis organic acidopathy - anion gap

Question 102

6 month old baby with pallor, hepatosplenomegaly, irritable. Xray shown with very white bones. Diagnosis: a. osteopetrosis b. vitamin D deficient rickets c. osteosarcoma

Answer 102

a. osteopetrosis Ca, PO4, ALP all normal

Question 103

Infant (a few weeks old?) with generalized tonic clonic seizure. He looks well and is well grown. Glucose is 1.7. The most important thing to measure is? a. Urine ketones b. Lactate/Pyruvate ratio c. Serum cortisol

Answer 103

a. Urine ketones

Question 104

Hypoglycaemia, low ketones, low FFA, high insulin in a macrosomic baby - what is the diagnosis?

Answer 104

hyperinsulinemic hypoglycemia of infancy

Question 105

Hypoglycaemic baby with reducing substances in urine - what is the diagnosis?

Answer 105

Galactosemia

Question 106

Hypoglycemia, micropenic, cleft palate, cholestatic jaundice - what is the diagnosis?

Answer 106

Hypopituitarism (midline defects)

Question 107

Hypoglycemia + hepatomegaly. What group of disorders to consider?

Answer 107

Glycogen storage disorders (like G6P deficiency)

Question 108

Glucose of 1.2, cardiomegaly on chest x-ray. What is the most likely etiology of this presentation? a. cardiac lesion b. sepsis c. inborn error of metabolism

Answer 108

c. inborn error of metabolism Pompe (type II glycogen storage disease) - cardiomegaly and macroglossia - glycogen accumulates in tissues which makes them large and not work well

Question 109

3 week baby with lethargy, poor feeding, and hepatomegaly. Has a normal lactate, ammonia, pH, CO2. What is the most likely diagnosis? a. Maple syrup urine disease b. Propionic academia c. Galactosemia d. Urea cycle defect

Answer 109

c. Galactosemia - hyperglycinemia also on the differential of an apparent metabolic disorder with normal ammonia and gas

Question 110

What is the most likely presentation of an inborn error of metabolism? a. encephalopathy preceding focal neuro deficit b. generalized hyper-reflexia c. abnormal pupillary reaction

Answer 110

a. encephalopathy preceding focal neuro deficit MELAS (mitochrondrial myopathy, encephalopathy, lactic acidosis, stroke-like episode) - mimics stroke with focal neuro defects

Question 111

A 3 month old is suspected of having an inborn error of metabolism, and has neurological and cardiac involvement. Which of the following can be given before a definitive diagnosis is made to prevent further sequelae: a. Thiamine b. Carnitine

Answer 111

b. Carnitine - good for organic acidemias, FAO defects, carnitine deficiency; lethargy and cardiomyopathy common presenting features of FAO defects B12: oragnic acidemia B6 (pyridoxine): seizures unresponsive to antiepileptics

Question 112

3 day old with lethargy, decreased level of consciousness and vomiting. On exam he has hyperpnea and respiratory alkalosis. His fontanelle is full and he has signs of mild increase in intracranial pressure. What is his diagnosis? a. Maple Syrup urine disease b. Urea cycle defect c. Encephalitis

Answer 112

b. Urea cycle defect

Question 113

Liver dysfunction long term complication of: a. MCAD b. OTC c. PKU d. Maple syrup urine disease

Answer 113

ANSWER: a. MCAD - lipid metabolism defect b. OTC - urea cycle defect c. PKU - amino acidemia d. Maple syrup urine disease - organic acidemia

Question 114

2½-year-old child is referred with language delay and inferior ectopia lentis. You should a) molecular studies for Marfan syndrome b) echocardiogram to rule out aortic root abnormalities c) fibroblasts/skin biopsy for enzyme d) quantitative serum amino acids e) platelet count and coagulation studies for hypercoagulability

Answer 114

d) quantitative serum amino acids Homocystinuria: IQ down, lens dislocated down Dx: elevated methionine or homocystine in blood or urine Tx: high dose vitamin B6

Question 115

Most likely to be associated with hearing loss: a) prematurity b) congenital CMV c) APGAR of 2 at 1 minute d) sibling with language delay e) furosemide given to mother during pregnancy

Answer 115

b) congenital CMV o TORCH (CMV most common acquired form of congenital hearing loss)

Question 116

Newborn who has webbed neck, lymphedema at hands and feet, hypertrophic cardiomyopathy (picture given- don’t think they told you if it was a girl or a boy) a) XO b) Noonans c)Williams

Answer 116

b) Noonans Turners is similar but has left sided heart defects (coarctation) - note primary hypogonadism - amenorrhea and infertility - not a feature of Noonan's

Question 117

Child with facial nevus in V1 distribution. Came to the hospital with focal seizure. What is the suspected diagnosis? What is the CT head finding expected? Name 2 other complications.

Answer 117

1. Sturge-Weber 2. CT head shows calcifications, MRI could show leptomeningeal angioma 3. complications: glaucoma, seizures, hemiparesis, intellectual disability, stroke-like episodes

Question 118

Picture of rocker bottom feet – what condition do you need to think about? What are 3 other features?

Answer 118

Edward syndrome (trisomy 18) - prominent occiput - clenched hands with overlapping fingers - prominent heels - small mouth and jaw, short neck

Question 119

Mother brings her son to see you for assessment of behaviour difficulties. He has been in generally good health. He is large (97, 95, 95%iles) and has prominent ears. He has a broad forehead and hyperextensible joints. Which of the following does he have? a) fragile X b) Klinefelters c) Sotos

Answer 119

a) fragile X fragile X : - remember large ears and long narrow face and hyperactivity

Question 120

5 mo with white forelock, 1 iris blue 1 brown. What next investigation would you do? What condition is this? a. Renal ultrasound b. Hearing test c. Echo cardiac d. Cranial ultrasound

Answer 120

b. Hearing test Waardenburg syndrome - sensorineural hearing loss common, non progressive

Question 121

An 8 year old otherwise well child has a hemi-vertebrae noted on CXR. What investigation will you do in the course of your work-up: a. MRI of the head b. MRI of the spine c. Abd U/S d. Echo

Answer 121

c. Abd U/S - VACTERL From genetics review - if it was a newborn would do an echo, but given healthy 8 year old, she probably doesn't have a serious cardiac lesion; don't know what's happening with kidneys though

Question 122

What are the components of VACTERL association?

Answer 122

vertebral defects anal atresia cardiac defects TEF renal anomalies limb anomalies (missing thumbs, underdeveloped forearms)

Question 123

Hemivertebra girl. What next imaging

Answer 123

AUS and echo

Question 124

Child has developmental delay. On exam you note that he is microcephalic, he has small palpebral fissures, a thin upper lip and a poorly defined philtrum. What is his diagnosis a. Cornelia De Lange b. Smith Lemli Opitz c. Fetal Alcohol Syndrome

Answer 124

c. Fetal Alcohol Syndrome

Question 125

A child who is described as having a learning disability, has big ears. Mom has an LD as well. What to tell mom to expect: a. Problems with tics b. Problems with athetosis c. Problems with hyperactivity d. Problems with tremor e. Problems with nystagmus

Answer 125

c. Problems with hyperactivity

Question 126

3 year old girl was normal developmentally for a while but has shown regression in the past year. Now she has microcephaly, and abnormal hand movements a. Retts b. Fragile X c. Autism d. TORCH infection e. childhood disintegrative disorder

Answer 126

a. Retts

Question 127

Child with supravalvular aortic stenosis, prominent lips, developmental delay, and hypercalcemia. This is indicative of: a. DiGeorge b. Williams c. Noonans d. Downs e. Fetal alcohol syndrome

Answer 127

b. Williams

Question 128

What are the components of DiGeorge syndrome?

Answer 128

- cardiac (TOF) - abnormal facies (hypertelorism, down slanting palpebral fissures, short philtrum) - thymic hypoplasia/T cell abnormality - cleft palate - hypocalcemia from hypoparathyroidism - 22q11 deletion

Question 129

Which feature is typical for achondroplasia? a. proximal limb shortening b. distal limb shortening c. short mid-portion of the bone d. non-specific shortening

Answer 129

a. proximal limb shortening

Question 130

In a patient with Romano-Ward syndrome, what would suggest the diagnosis: a. presence of cafe-au-lait spots b. congenital defects c. sensorineural hearing loss d. family members have it

Answer 130

d. family members have it - cardiac syndrome, long QT, family history is key - most cases inherited from an affected parents, few cases are de novo mutations; inheritance is AD with incomplete penetrance \*Long QT plus congenital deafness (SNHL) = Jervell and Lange-Nielson syndromes (autosomal recessive)

Question 131

Fetal alcohol syndrome a. 4 facial dysmorphisms b. 2 clinical features of the syndrome

Answer 131

a. smooth philtrum, thin upper lip, short palpebral fissures, micrognathia b. microcephaly, intellectual disability, small stature

Question 132

Photo shown of infant with short palpebral fissures, smooth philtrum, short nose and thin upper lip. He presents with irritability. This infant’s condition is due to maternal exposure to: a) cocaine b) heroin c) cigarettes d ) alcohol e) Dilantin

Answer 132

d ) alcohol

Question 133

Which is a common characteristic in fetal hydantoin syndrome: a) microcephaly b) hypoplastic nails c) intrauterine growth restriction d) seizures e) cataracts

Answer 133

b) hypoplastic nails fetal hydantoin - fetus exposed to hydantoin (phenytoin)

Question 134

List 4 screening tests you would routinely do for a child with Down's Syndrome

Answer 134

- ophtho exam for strabismus, cataracts, nystagmus - hearing test - q6 months until bilateral hearing test possible - screen for hypothyroidism annually - screen for celiac (symptoms annually, BW PRN) - hemoglobin screen annually

Question 135

Child with trisomy 21. 3 discrete round completely hairless areas on the scalp. No other findings. a. What is the most likely diagnosis? b. What will you tell mom is the natural history of this problem

Answer 135

a. alopecia areata b. ● Spontaneous resolution in 6-12 month ● Recurrence: common

Question 136

Child with Down syndrome. List three associated hematological disorders

Answer 136

● Neonatal polycythemia ● Neonatal leukemoid reaction ● Transient myeloproliferative disorder ● Anemia (iron deficiency due to poor intake) ● Leukemia (1%)

Question 137

Family physician calls you about term neonate who weighs 2300 g. Neonate has lymphoedema, low set hair line and wide chest. What test would you send for diagnosis?

Answer 137

Probably Turner as opposed to Noonan because is term and very small. Noonan not usually SGA. - Karyotype for Turner, RASopathy panel for Noonan

Question 138

List two investigations that should be done in a neonate with suspected Turner syndrome and their expected findings

Answer 138

AUS - horseshoe kidneys 4 limp BP and echo - aortic valvular disease (bicuspid aortic valve), or coarctation

Question 139

Scenario of a boy with Fragile X. Mom is a carrier. There is a sister in the family. Mom asks you if you could test the sister to see if she is a carrier. She is currently in grade 5 and doing well. Do you test the daughter?

Answer 139

No! If she is healthy, then the recommendation is to wait until she is an adult and can make her own decisions about what she wants to know. Counsel that she may want investigations before pregnancy if she wants to know about potential risk for her children.

Question 140

5 Clinical features of turners and 2 cardiac complications

Answer 140

1. hearing loss, strabismus, shield chest, widely spaced nipples, increased carrying angle of arms, short stature, ovarian failure, hypothyroidism 2. bicuspid aortic valve, coarctation of aorta

Question 141

List 3 features of Pierre-Robin sequence.

Answer 141

micrognathia, retrognathia high arched palate/cleft palate glossoptosis (tongue drops back and obstructs because it is relatively large for the oral cavity)

Question 142

Child with suspected Duchenne muscular dystrophy. a. What is diagnostic on biopsy (be specific)? b. What 2 things do you want to know to help with genetic counseling?

Answer 142

a. lack of dystrophin in myofibers, endomysial connective tissue proliferation b. X-linked recessive condition (2/3 inherited) - what is the specific genetic defect in the child? - is mom a carrier of this defect - if yes, 50% chance or having another boy with DMD, if no, was a spontaneous mutation and there is no risk - is the family planning to have more children?

Question 143

Child with hemihypertrophy. What condition would you suspect that would require serial follow-up?

Answer 143

Beckwith-Wiedemann ● Cancer risk high until 8 y.o. (~7.5%) o Need regular surveillance with abdo US + alpha fetoprotein measured every 3 mon. until 8 y.o. o Then Renal US every 1-2 year as medullary sponge kidney and nephrocalcinosis can happen later

Question 144

Child with Wilm’s tumor. Which is associated? a. Down syndrome b. Prader-Willi syndrome c. Beckwith-Weideman d. Angelman’s syndrome

Answer 144

ANSWER: c. Beckwith-Weideman – Wilm’s Tumour, Hepatoblastoma, Neuroblastoma, Adrenocortical carcinoma a. Down syndrome – acute myeloid leukemias

Question 145

Cancers are associated with several disease states. Name one cancer associated with each of the following. - Beckwith Wiedemann - Down syndrome - Aniridia

Answer 145

- Beckwith Wiedemann- Wilm’s, Hepatoblastoma, higher risk of neuroblastoma - Down syndrome – Leukemia (Specifically acute myeloid leukemia) - Aniridia – Wilm’s Tumour

Question 146

3d old term infant with absence of abd muscles and undescended testes bilaterally. TFI 90/kg/d. Na 120, K 5, Glu 2.6, normal urea, creatinine 119. U/O 10 cc in last 24 hrs. Kid NPO. Wt 4kg. What is causing this kid's problems?

Answer 146

Prune belly syndrome - obstructive uropathy

Question 147

Alpha-1 antitrypsin. Most likely presentation in children? a. jaundice b. emphysema c. bronchiectasis d. pneumonia

Answer 147

a. jaundice

Question 148

Boy with MELAS, what do you tell him is his risk of passing it on to his kids?

Answer 148

Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes - no chance of passing it on to his kids because mitochondrial disorders are all inherited maternally

Question 149

Child with distress, cannot pass NG through nares. Choanal atresia. List 3 other findings on physical exam you’d look for?

Answer 149

CHARGE (CHD7 gene mutation) Coloboma Heart defects (TOF, AV canal) Atresia choanae Retardation of growth (short stature) and motor development GU abnormalities (micropenis, cryptorchidism, hypoplastic labis in females) Ear deformities/hearing loss

Question 150

Mother with DiGeorge syndrome has a child with cleft-palate. What 3 things should you do for investigation/management in the child (3)?

Answer 150

- check calcium (hypocalcemia) and PTH (hypopara) - echo (TOF, truncus arteriosus) - renal U/S (renal hypoplasia) - immunodeficiency W/U: CBC and diff, T and B cell numbers, immunoglobulins - CXR for absence of thyme silhouette

Question 151

List 4 features of Rett syndrome.

Answer 151

1. loss of previously acquired developmental milestones 2. repetitive hand wringing, and loss of purposeful hand movements 3. acquired microcephaly 4. seizures 5. ataxia 6. poor weight gain

Question 152

3 major skeletal diagnostic criteria for Marfans?

Answer 152

1. armspan greater than height 2. lower segment longer than upper segment 3. hindfoot deformity 4. pectus carinatum 5. positive thumb sign and wrist sign 6. scoliosis or thoracolumbar kyphosis 7. reduced elbow extension 8. protrusio acetabulae

Question 153

Give a condition that corresponds to coloboma

Answer 153

CHARGE syndrome Wolf-Hirschorn syndrome 13q deletion syndrome

Question 154

Give a condition that corresponds to dislocated lens

Answer 154

Marfan's (superior dislocation) Homocysteinuria (inferior dislocation)

Question 155

Give a condition that corresponds to aniridia

Answer 155

WAGR (Wilms tumour, aniridia, GU abnormalities, MR) Miller syndrome (aniridia with Wilm's tumour)

Question 156

Give a condition that corresponds to glaucoma

Answer 156

Sturge Weber Trisomy 21 NF1 Mucopolysaccharidoses

Question 157

List 4 non-infectious risk factors of hearing loss in the newborn period.

Answer 157

- family history of hearing loss - outer ear malformation/craniofacial malformations - apgars 0-4 at 1 minute - NICU stay \>2 days - ototoxic drug use - hyperbili needing exchange transfusion - mechanical ventilation

Question 158

Which of the following is characteristic of Rett syndrome: a. ataxia b. seizures c. head bobbing d . hand wringing e. admit and place on a Phenylalanine free diet

Answer 158

d . hand wringing

Question 159

A 25 year old mother of a child with Down syndrome (47XY (+21)) comes for advice regarding subsequent pregnancies. : a. no advice can be offered until karyotype of parents is known b. no antenatal workup needed as recurrence risk is \<5% c. if level 2 ultrasound is abnormal at 16 weeks, then do amniocentesis d. antenatal karyotyping should be done with all subsequent pregnancies e. Chromosomes should be offered for any future pregnancy

Answer 159

e. Chromosomes should be offered for any future pregnancy - the recurrence risk is small but it's still reasonable to offer prenatal testing if the family wants (47XY (+21)) - this is your standard T21 karyotype (would be different if there was a translocation in which case the parents would need to be tested and risk of recurrence is much higher)

Question 160

A 20-year-old mother and 25-year-old husband have just had a child with clinical features of Down syndrome. What is the most likely karyotype: a) trisomy 21 b) mosaicism c) translocation 14/21 d) translocation 21/22

Answer 160

a) trisomy 21

Question 161

Which of the following is done routinely in a 1-week-old infant with trisomy 21: a) lateral c-spine films b) abdominal ultrasound c) ophthalmology consult d) auditory brainstem response e) do nothing

Answer 161

e) do nothing standard OAEs for hearing testing are fine

Question 162

In the follow-up of a child with Down syndrome, which would be appropriate: a) CBC and smear b) lipid studies c) thyroid function d) hepatitis B serology e) antigliadin antibody

Answer 162

c) thyroid function - TSH on newborn screen, then at 6 & 12 months, then annually a) CBC and smear - technically do not need a smear, just a CBC annually

Question 163

You diagnose a boy as having fragile X by DNA testing. His sister is performing poorly at school, and parents are concerned that she has fragile X. You: a. order DNA testing on sister to rule out fragile X b. order cytogenetics on sister to see if she is a carrier c. order cytogenetics on mother to she if she is a carrier d. do nothing - females do not get fragile X

Answer 163

a. order DNA testing on sister to rule out fragile X DNA testing is the same as molecular testing; in fragile X you specifically need DNA PCR to make the diagnosis cytogenetics is microarray, FISH and karyotype

Question 164

In a child with Fragile X, all would be present EXCEPT: a) motor delay b) speech delay c) microcephaly d) large ears e) autistic-like features

Answer 164

c) microcephaly They have large heads

Question 165

Which condition is associated with macroglossia and an umbilical hernia: a) congenital hyperthyroidism b) infant of a diabetic mother c) Beckwith-Wiedemann syndrome d) Down syndrome

Answer 165

c) Beckwith-Wiedemann syndrome

Question 166

A 1-month-old child has macroglossia, hemihypertrophy, and an umbilical hernia, consistent with Beckwith-Wiedemann syndrome. You recommend the following: a) CT head b) regular abdominal ultrasounds c) intermittent checks for hypoglycemia d) measurement of leg-length discrepancy e) DNA testing for Beckwith-Wiedemann syndrome

Answer 166

b) regular abdominal ultrasounds Re DNA testing - can make clinical diagnosis if 3 major criteria are present

Question 167

Characteristics of Schwachman-Diamond syndrome a) decreased pancreatic enzyme excretion b) normal neutrophil count c) hypocellular bone marrow d) increased risk of diabetes mellitus

Answer 167

a) decreased pancreatic enzyme excretion - malabsorption, FTT - also have neutropenia/myelodysplastic syndrome, bone marrow failure - make cells but cannot push them out, so marrow is not hypocellular - bone abnormalities (thoracic dystrophy)

Question 168

Which of the following findings would help to rule out Klinefelter syndrome: a) normal upper/lower body segment ratio b) muscular habitus c) testosterone level 5.0 d) testicular volume of 15 cc e) behavioural/learning difficulties

Answer 168

d) testicular volume of 15 cc - have small testes (prepubertal even - 4ml) - all the other options do also go against Klinefelters, but not strongly enough to rule it out

Question 169

Picture of child with Down Syndrome. Child noted to be hypotonic. Term, normal Weight. Questions is what test most expediously confirms diagnosis. a. Chromosome analysis b. TSH, T4 c. Muscle biopsy

Answer 169

a. Chromosome analysis FISH or rapid aneuploidy testing would be quickest way get diagnosis (TAT 24-48h); but still need to do a karyotype after to see if there is a translocation

Question 170

1 week old infant with T21. What should be done prior to discharge home? a. ABR b. Ophthalmology consult c. Abdo U/S d. Echocardiogram

Answer 170

d. Echocardiogram

Question 171

14 y.o. with T21. What test should be done annually? a. X-ray of cervical spine b. TSH c. Audiology d. Ophthalmologic exam

Answer 171

b. TSH c. Audiology

Question 172

vomiting infant with T21, next step? what are you worried about?

Answer 172

AXR - concern is for duodenal atresia; also consider Hirschsprung, bad GERD

Question 173

Beckwith-Wiedeman syndrome U/S. A question about how frequently ultrasound should be done.

Answer 173

- AUS q3 months until age 8 - then annually from age 8-mid adolescence for kidney abnormalities, especiallymedullary sponge kidney

Question 174

Child with Wilm’s tumor. Which is associated? a. Down syndrome b. Prader-Willi syndrome c. Beckwith-Weideman d. Angelman’s syndrome

Answer 174

c. Beckwith-Weideman

Question 175

Child with large port wine stain in a distribution of the 1st trigeminal nerve. What do you work him up for? a. optic glioma b. cerebral arteriovenous malformation c. glaucoma d. liver disease

Answer 175

c. glaucoma (Concern is for Sturge Weber)

Question 176

Picture of a baby sucking on a pacifier and looking relatively content. Severe thrombocytopenia. Has a large lesion overlying his left forehead and eyelid (not a port-wine stain). What is the most likely finding on labs? a. normal INR and PTT b. elevated fibrinogen c. schistocytes and RBC fragments on smear d. neutropenia and anemia

Answer 176

c. schistocytes and RBC fragments on smear Kasabach-Merritt syndrome (hemangioma with thrombocytopenia) -fibrinogen is decreased - can have anemia (MAHA), but not neutropenia

Question 177

Trisomy X - symptoms?

Answer 177

* Tall stature * Hypotonia * Abnormal clinodactyly * Language based learning disorder, dyslexia * Anxiety * ADHD

Question 178

Stickler syndrome

Answer 178

* Features: * Pierre-Robin syndrome * Myopia and ophtho complications (choroidoretinal and vitreous degeneration, retinal detachment) * SNHL * joint hypermobility * Do eye exam in Pierre Robin to look for Sticklers

Question 179

What is risk of healthy child being carrier of CF when sibling has CF?

Answer 179

66% Since they are healthy, they can't have CF, so ⅔ = 66% of punnett square