1. What is the characteristic triad of features in McCune-Albright Syndrome?
    • Polyostotic fibrous dysplasia
    • Cafe-au-lait skin pigmentation
    • Autonomous endocrine hyperfunction
  2. What does the gene involved in McCune-Albright syndrome encode for?
    Alpha subunit of a G-protein
  3. What is the proposed mechanism for the phenotype resulting from the mutation of the G protein in McCune-Albright syndrome?
    • Mutation in G protein --> inactivation of intrinsic GTPase activity --> prevents inactivation of Gs alpha subunit once activated --> continuous stimulation of AC even in absence of ligand binding to receptor --> increased intracellular cAMP and continual stimulation of downstream cAMP signalling cascades
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  4. How does the pattern of inheritance of McCune-Albright syndrome result in the variable phenotype?
    • Post zygotic somatic mutation
    • -- All daughter cells of embryonic cell inwhich mutation occurs contain mutation
    • -- the earlier in embryogenesis that the mutation occurs the more widespread the involvement
  5. What is the most common endocrine features of McCune-Albright syndrome?
    Precocious puberty
  6. What is the cause of precocious puberty in McCune-Albright syndrome and what are the ramifications for growth?
    • result of gonadotropin independent autonomous ovarian or testicular function
    • results in sexual precocity, increased growth velocity and advanced skeletal maturity
  7. What are the endocrine features of McCune-Albright syndrome?
    • ACTH-independent Cushings syndrome (growth failure and HTN in infancy)
    • Hyperthyroidism (autonomous hyperfunctioning nodules)
    • Growth hormone excess (from somatotroph adenomas in the pituitary)
  8. What are the non-endocrine features of McCune-Albright syndrome?
    • Fibrous dysplasia - most commonly affecting long bones, ribs ans skull
    • Cafe-au-lait spots - large melanotic macules which do not cross the midline
    • Hypophosphataemia - decreased reabsorption of phosphate in the renal tubule
    • Hepatic abnormalities
  9. Which genetic mutations are associated with Rubinstein-Taybi syndrome?
    • CBP (CREBBP) - CREB binding protein - Chr 16p13
    • EP300 - EA1 binding protein p300 - Chr 22q13
  10. What are the characteristic facial abnormalities seen in Rubeinstein-Taybi syndrome?
    • Hypoplastic maxilla with narrow palate
    • prominent beaked nose
    • low set ears
    • large anterior fontanelle
    • microcephaly
    • small mouth
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  11. What are the digital abnormalities seen in Rubenstein-Taybi syndrome?
    • Broad great toes
    • Broad thumbs with radial angulation
    • Broad fingers
    • Persistent foetal finger pads
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  12. What are the features of Rubenstien-Taybi syndrome?
    • Characteristic facial and digital abnormalities
    • Strabismus, congenital glaucoma, retinal abnormalities
    • Delayed osseous maturation
    • Cardiac abnormalities
    • Hirsutism
    • Capillary nevus of forehead or nape
  13. What does is IPEX an acronym for?
    • Immunodysregulation
    • Polyendocrinopathy
    • Enteropathy
    • X-linked
  14. What triad of disorders does IPEX syndrome typically present with?
    • Life threatening chronic diarrhoea due to an autoimmune enteropathy
    • Autoimmune endocrinopathy (neonatal type 1 diabetes or thyroiditis)
    • Dermatitis, usually eczematous
  15. What is the genetic basis of IPEX?
    • Caused by mutations in the gene for the transcription factor Foxp3 - located on Chr xp11.23
    • Foxp3 is a member of the forkhead box P (FOXP) family of transcription factors
    • - fundamental to the function of the subset of T lymphocytes know as regulatory T cells
  16. What are the gastrointestinal manifestations of IPEX?
    • Autoimmune enteropathy - chronic intractable diarrhoea with failure to thrive
    • Protein losing enteropathy
    • Severe food allergy
    • Autoimmune hepatitis
  17. What are the common skin findings in IPEX?
    • Dermatitis - eczematous rash
    • Diffuse erythema
    • alopecia universalis
    • Psoriasiform rashes
    • Painful fissurary chelitis
    • Pemphigoid nodularis
  18. What are other features can be present in IPEX?
    • Haematologic disorders - Coombs positive haemolytic anaemia, autoimmune thrombocytopenia, autoimmune neutropenia
    • Exaggerated response to infection
    • Renal disease - interstitial nephritis
    • Developmental delay
    • Pulmonary disease - infection related, interstitial lung disease, ABPA
  19. What are the features of Aicardi syndrome?
    • Myoclonic seizures
    • Agenesis of corpus callosum
    • Lacunar chorioretinopathy
    • Microphthalmia
    • Developmental delay
    • Hemivertebrae
    • Hepatoblastoma
  20. What are the characteristic features of EEG in Aicardi syndrome?
    Periodic asynchronous discharges from left and right hemispheres
  21. What are the characteristics of Alagille Syndrome?
    • Paucity of intrahepatic bile ducts - cholestasis and conjugated hyperbilirubinaemia
    • Peripheral pulmonary artery stenosis
    • Butterfly vertebrae
    • Posterior embryotoxon
    • Characteristic facies
  22. What are the facial features of Alagille syndrome?
    • Broad forehead
    • Deep set, widely spaced eyes
    • Long straight nose
    • Underdeveloped mandible
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  23. What genes are involved in Alagille syndrome?
    • NOTCH2 or JAG1
    • Autosomal dominent inheritence
  24. What are the clinical features of Angelman's syndrome?
    • Puppet like gait, ataxia
    • Paroxysms of laughter
    • Characteristic facies
    • Seizures
    • Cerebral atrophy
    • Absent speech
  25. What are the facial features of Angelman's syndrome?
    • Deep set eyes
    • Large mouth with prognathia
    • Wide spaced teeth
    • Tongue protrusion
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  26. What is the genetic basis for Angelman syndrome?
    • Deletion on Chromosome 15 encoding UBE3A, involved in ubiquitin pathway.
    • Maternal UBE3A gene is expressed and paternal gene is silenced - imprinting
    • Uniparental disomy accounts for some rare cases
  27. What are the features of Apert syndrome?
    • Irregular craniosynostosis
    • Midface hypoplasia
    • Symmetrical syndactyly of hands and feet - 2nd-4th digits
Card Set
Features of genetic syndromes