Which of the the Urea Cycle defects is not autosomal recessive?
- Ornithine transcarbamylase (OTC) deficiency is X-linked.
- All males of a carrier female will be affected
- 10% of female carriers are also affected
- Risk of further child inheriting the disorder >50%
- If parents know the gender of their child more specific advice can be given: 50% chance of affected male, 10% chance of affected female
- Males generally more severely affected
What syndrome is associated with mutation of CHD7 gene?
- CHARGE syndrome Coloboma Heart defects choanal Atresia Retarded growth GU defects Ear anomalies - CHD7 on 8q11
What syndrome is associated with mutation of PAX2 gene?
- Renal-coloboma syndrome
- coloboma, renal abnormalities, SNHL, seizures and joint laxity.
Which disorders are due to mutations in fibroblast growth factor receptor (FGFR)?
- Achondroplasia group.
- -> thanatrophoric dysplasia, achondroplasia, hypochondroplasia.
What are manifestations of achondroplasia?
- Manifests at birth.
- AD but most cases sporadic.
- FGFR3
- Short limbs, long narrow trunk, midfacial hypoplasia and prominent forehead.
- Limb shortening greatest in proximal segments.
- Fingers often display trident configuration.
- Infants often have delayed motor milestones.
- Spinal canal stenotic, can experience expression at level of foramen magnum. Can result in quadraparesis, central apnoea and sudden death.
What components are identified by different blot techniques?
- Southern blot identifies DNA.
- Northern blot identifies RNA.
- Western blot identifies protein.
What is the inheritance of retinitis pigmentosa?
- Group of inherited dystrophies characterised by progressive degeneration and dysfunction of the retina, primarily affecting photoreceptor and pigment epithelial function.
- May occur alone or as part of a syndrome.
- May be inherited as part of a syndrome, recessive, dominant or X-linked trait.
- Typical form (non-syndromic) in which manifestations are restricted to the eye comprises 65% of cases.
Describe Usher syndrome.
- Most common form of syndromic retinitis pigmentosa.
- Congenital or early onset hearing impairment followed by development of RP.
Describe Bardet-Biedl syndrome.
- Second most common syndromic form of retinitis pigmentosa.
- Associated with polydactyly, obesity. renal abnormalities and mental retardation.
- Cal also be associated with micro-orchidism, polyuria and polydipsia.
- Autosomal recessive. Mutations involving nephronophthisis (NPHP) gene well characterised and cause childhood endstage renal failure and retinitis pigmentosa.
What are the causes of pigmentary retinopathy?
- Retinitis pigmentosa (non-syndromic).
- Usher syndrome.
- Bardet-Biedl syndrome.
What are the features of incontinentia pigmenti?
- X-linked dominant.
- Generally lethal in males, resulting in miscarriage.
- Erythematous linear streaks with plaques of vesicles along Blaschko lines, appear in 1st 3 weeks.
- 80% have dental abnormalities.
- 1/3 neurological involvement - seizures, microcephaly, developmental delay/intellectual impairment.
- 30% ocular involvement - cataract, optic nerve atrophy and retrolenticular masses.
What are the stages of incontinentia pigmenti?
- Stage 1: vesicular.
- Stage 2: verrucous.
- Stage 3: Hyperpigmented.
- Stage 4: Atrophic/hyperpigmented.
Which gene is responsible for reduced growth and development in Turner syndrome?
- SHOX gene.
What are features of Loeys-Dietz syndrome?
- Mutation in transforming growth factor (TGF-b) receptors.
- Autosomal dominant.
- Triad of arterial tortuosity and aneurysms, hypertelorism and bifid uvula.
Describe Papillon-Lefevre syndrome.
- Rare AR disorder.
- Mutation CTSC gene - regulates production of cathepsin C.
- Palmoplantar hyperkeratosis and immunodeficiency (pyogenic infections - liver abcesses etc).
- Aggressively progressive peridontitis leads to premature loss of deciduous and permanent teeth.
What are features of Apert syndrome?
- AD
- FGFR2 gene.
- Bicoronal cranial synostosis.
- Maxillary hypoplasia, hypertelorism, syndactyly.
What are features of Muenke syndrome?
- AD
- FGFR3 mutation.
- Single coronal synostosis.
- Sensorineural hearing loss, facial asymmetry, flattened cheek bones, normal hands and feet.
- 1/3 have developmental delay.
What are features of craniofrontonasal syndrome?
- X-linked dominant.
- EFNB1 gene.
- Coronal synostosis, grooved nasal tip, cleft lip and palate, grooved nails.
What are features of Pfeiffer syndrome?
- AD
- FGFR2 and 1.
- Variable sutures involved.
- Broad thumbs that deviate medially.
What are features of Crouzon syndrome?
- AD
- FGFR2 and 3.
- Bicoronal synostosis.
- Proptosis, beaked nose, midface hypoplasia, normal hands and feet.
What are features of Saethre-Chotzen syndrome?
- AD.
- TWIST1.
- Coronal sutures.
- Ptosis, hypertelorism, low anterior hair line, moderate developmental delay.
What are features of Carpenter syndrome?
- AR.
- RAB23.
- Multiple sutures.
- Flat nasal bridge, shallow supraorbital ridges, hypoplastic mandible, low set ears, cardiac involvement 50%.
Describe Costello syndrome.
- Mutation in HRAS leads to increased growth an division.
- Coarse face, epicanthal folds, depressed nasal bridge and deep creases in the palm.
- 50% cardiac defects which include valvulr pulmonary stenosis, HCM, aortic dilatation as well as ASD and VSD.
- Increased risk of malignant and non-malignant tumours with papillomas the most common and earliest.
What are features of Rubenstein-Taybi syndrome?
- Short stature.
- Hirsuitism.
- Downslanting palpebral fissures.
- Maxilary hypoplasia.
- Prominent nose with nasal septum extending below alae nasi.
- Low posteriorly rotated ears.
