Genetics

Question 1

Waardenburg’s syndrome

Answer 1

AD
Abnormal distribution of melanocytes, which results in patchy areas of depigmentation, loss of pigmentary cells in eyes, skin, stria vascularis of the cochlea, and hair. A broad nasal root, lateral displacement of medial canthi with the dystopia of lacrimal puncta, pigmentary abnormalities of the iris, hypertrichosis of the medial part of the eyebrows, white forelock, and congenital unilateral or bilateral sensorineural hearing loss characterize it.

Question 2

Wiskott-Aldrich syndrome

Answer 2

X-linked recessive disorder that results in partial B and T cell deficiencies through a defective cytoskeletal glycoprotein, low levels of CD43 expression on lymphocytes.

Eczema, recurrent infections, and thrombocytopenia, B cell malignancies.
Increased IgE and IgA, and decreased IgM.

Question 3

Beckwith-Wiedemann syndrome

Answer 3

Pediatric overgrowth disorder caused by a mutation on chromosome 11.
Fetal macrosomia, macroglossia, hemihypertrophy, midline defects such as omphalocele or umbilical hernia, and neonatal hypoglycemia due to fetal hyperinsulinemia.
predisposes patients to embryonal tumor development, including Wilms tumor, hepatoblastoma, and neuroblastoma.

Question 4

47 XYY

Answer 4

a sex chromosome aneuploidy, in males.
tall, severe acne
some patients have learning disabilities, slow motor progression and few autistic features.
Normal levels of sex hormones and normal secondary sexual development.
Depression, anxiety.

Question 5

Myotonic dystrophy

Answer 5

The most common adult muscular dystrophy.
Selective atrophy of type 1 muscle fibers.
Trinucleotide CTG repeat in the DMPK gene which leads to an abnormal myotonin protein kinase.
Facial weakness, myotonia (often manifesting as an inability to relax hand grip such as when shaking hands), cardiac conduction abnormalities, frontal balding, cataracts, and muscle wasting.
There are no disease-modifying treatments so supportive care with pacemakers, cataract surgery, and ventilatory support may be indicated.

Question 6

Wiskott-Aldrich syndrome

Answer 6

X-linked recessive condition
eczema, microthrombocytopenia, and recurrent infections due to a defect in the WAS gene, affecting cytoskeleton remodeling in hematopoietic cells.
This leads to immune dysfunction and increased infection risk, low platelet counts and size and autoimmune disorders are common.
Treatment: hematopoietic stem cell transplantation.

Question 7

Von Hippel-Lindau disease

Answer 7

AD
Mutation in the VHL tumor suppressor gene on chromosome 3.
Cerebellar and retinal hemangioblastomas, pheochromocytoma, and clear cell renal cell carcinoma.

Management: surveillance for malignancies through eye examinations, plasma or urine metanephrines, MRI of the brain, spine, and abdomen, as well as tumor resection.

Question 8

Diamond-Blackfan anemia

Answer 8

Congenital erythroid aplasia, craniofacial abnormalities, triphalangeal thumbs, and an increased risk of malignancy.
Macrocytic anemia, reticulocytopenia, with normal platelets and white blood cells. Treatment: corticosteroids and red blood cell transfusions.

Question 9

Trisomy 18

Answer 9

Edwards syndrome is characterized by low birth weight, fetal growth restriction, microcephaly, ventricular septal defect, closed fists with overlapping fingers, micrognathia, prominent occiput, rocker-bottom feet, and severe intellectual disability.

Question 10

Friedreich ataxia

Answer 10

The most common hereditary form of ataxia.
Autosomal recessive.
Presents with progressive ataxia in adolescence, caused by an excessive number of trinucleotide repeat sequences (most commonly GAA) in the frataxin gene. Neurologic findings: dysarthria, limb weakness, loss of deep tendon reflexes, and progressive gait and limb ataxia. Loss of position and vibratory senses, kyphoscoliosis and pes cavus (high-arched feet).
Hypertrophic cardiomyopathy occurs in most patients, with an increased risk of arrhythmia and heart failure, usually leading to death by age 40.
Imaging: cervical spinal cord atrophy.

Question 11

Sturge-Weber syndrome

Answer 11

Neurocutaneous disorder
Facial port-wine stain, leptomeningeal capillary-venous malformations, and glaucoma, resulting from a congenital anterior chamber angle anomaly.

Question 12

Wilson disease

Answer 12

AR
Hepatic copper accumulation and tissue deposits (e.g., basal ganglia, cornea).
Clinical findings: hepatic issues (acute liver failure, cirrhosis), neurologic symptoms (parkinsonism, gait disturbance), and psychiatric symptoms (depression, psychosis).
Diagnosis:↓ ceruloplasmin, ↑ urinary copper, Kayser-Fleischer rings, and liver biopsy showing increased copper.
Treatment: chelators (D-penicillamine, trientine) and zinc to reduce copper absorption.

Question 13

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)

Answer 13

AD
Diffuse telangiectasias, recurrent epistaxis, and widespread arteriovenous malformations commonly occur in mucous membranes, skin, and the gastrointestinal tract, but can also affect the liver, brain, and lungs. Pulmonary AVMs may cause right-to-left shunting, leading to chronic hypoxemia, digital clubbing, reactive polycythemia, and possibly massive hemoptysis.