Chromosomal anomalies/Single gene Disorders/Syndromes Flashcards
What are the characteristic features of Noonan Syndrome?
- dysmorphic facies
- short stature
- webbed neck
- lymphatic abnormalities
- skeletal deformities
- bleeding diatheses
- renal diseases
- variable intellectual disabilities
- cardiac anomalies
True or false: Noonan syndrome affects more male than female?
FALSE
Equally affects males & females
What is the inheritance pattern of Noonan Syndrome?
Most cases are sporadic but can be inherited as an autosomal dominant trait
- What is the name of the group of genetic diseases of which Noonan Syndrome is part of?
- What are other syndromes included in this group?
- Why is the group named that way?
- RASopathies
- LEOPARD Syndrome
- Costello Syndrome
- Craniofaciocutaneous (CFC) syndrome
- Disorder of the RAS/mitogen-activated protein kinase (MAPK) pathway
What is the gene most commonly mutated in Noonan Syndrome?
- PTPN11 (chromosome locus 12q24.1)
What are some other genes known to cause Noonan Syndrome?
- SOS1 **
- KRAS **
- RAF1
- NRAS
- BRAF
- SHOC2
What syndrome is also known as the “heart-hand” syndrome?
Holt-Oram Syndrome
What are the main extracardiac findings in Holt-Oram Syndrome?
Preaxial radial ray malformations such as
- thumb anomalies (triphalangeal)
- radius aplasia
- phocomelia
- *Skeletal findings can be unilateral or bilateral
What are the main extracardiac findings in Alagille Syndrome?
- Biliary anomalies (bile ducts paucity, cholestasis)
- Facial dysmorphism (broad forehead, pointed chin, inverted triangle appearance)
- Cerebral arterial vasculopathy with aneurysms
What is the inheritance pattern of Tuberous Sclerosis Complex?
- Autosomal dominant
BUT
2/3 of patients have a de novo mutation
Which 2 genes are most commonly affected in tuberous sclerosis?
- TSC1
- TSC2
- mutations in the gene TSC1 produce milder sx than mutations in TSC2 gene
What are the main features of tuberous sclerosis?
- multisystem hamartomas (brain, cardiac rhabdomyomas, renal angiomyolipoma, facial angiofibroma)
- Epilepsy
- Café-au-lait skin lesions
What does a mutation in TSC1 or TSC2 cause?
Affects the proteins hamartin & tuberin –> modulator of mTOR signaling pathway which is important in regulation of cell growth
–>Abnormal coding leads to an increased tumor occurence
What is CHARGE syndrome?
C = Coloboma of iris or retina H = heart defects A = choanal atresia R = growth restriction G = genital anomalies E = ear anomalies or deafness
- variable clinical spectrum
What is the most common affected gene in CHARGE syndrome?
CHD7 gene
What is the inheritance pattern of CHARGE syndrome?
Most cases are sporadic (de novo mutation)
BUT
autosomal dominant inheritance & germ-line mosaicism are possible
