Genetic syndromes

Question 1

What causes prader-Willi syndrome?

Answer 1

Deletion or mutation of paternal gene copy of 15q11-q13 and maternal gene methylation (silencing)

Question 2

What are the clinical features of prader-willi syndrome?

Answer 2

• Muscular hypotonia and poor feeding in infants
• Increased appetite (hyperphagia) and obesity
• Short stature , scoliosis
• Cryptorchidism, hypogonadism , genital hypoplasia
• Facial dysmorphia (e.g., almond-shaped eyes, thin upper lip)
• Premature adrenarche with early development of pubic/axillary hair
• Developmental delays (e.g., delayed achievement of milestones), intellectual disability
• Behavioral problems (e.g., temper tantrums, stubbornness, obsessive-compulsive behavior)

Question 3

What are the main clinical features of prader-willi which would help to distinguish from other syndromes?

Answer 3

All the H’s
* Hypogonadism
* Hypotonia
* Hyperphagia -> obesity

Question 4

What causes Williams syndrome?

Answer 4

microdeletion of the long arm of chromosome 7 (includes a deletion of the elastin gene)

Question 5

What are the clinical features of Williams syndrome?

Answer 5

• Intellectual disability
• Hypersociability (e.g., comfort with strangers), good verbal skills
• Characteristic facial features (elfin facies):
• Midfacial hypoplasia,
• Short palpebral fissure
• Wide forehead
• Flattened nasal bridge, anteverted nostrils
• Long philtrum
• Hypodontia
• Cardiovascular malformations (esp. supravalvular aortic stenosis, renal artery stenosis)
• Hypercalcemia (due to increased sensitivity to vitamin D)
• Low muscle tone
• Hyperacusis, phonophobia
• Potential malformations and development problems in multiple organ systems, such as starburst-like pattern in the iris (“stellate iris”)

Question 6

What are specific features which may help distinguish williams syndrome from other genetic abnormalities?

Answer 6

William takes ICEcream from strangers (Intellectual disabilities, Cardiovascular malformations, Elfin-like facial features, comfort with strangers).

• Short stature
• Learning difficulties
• Friendly, extrovert personality
• Transient neonatal hypercalcaemia
• Supravalvular aortic stenosis

Question 7

What is the main cardiac abnormality often seen in williams syndrome?

Answer 7

Supravalvular aortic stenosis

Question 9

What are the clinical features of pierre-robin syndrome?

Answer 9

• Cleft palate
• Glossoptosis (retraction of the tongue in the pharynx) with possible complications such as acute respiratory distress and aspiration
• Mandibular retrognathia (posterior mandibular positioning) or micrognathia (small lower jaw)
• Possible intellectual disability

Question 10

What clinical features may help distinguish pierre robin from other genetic syndromes?

Answer 10

• Micrognathia
• Posterior displacement of the tongue (may result in upper airway obstruction)
• Cleft palate

Question 11

What causes noonan syndrome?

Answer 11

autosomal dominant condition with a heterogeneous clinical picture due to mutation in the PTPN11 gene on chromosome 12

Question 12

What are the clinical features of noonan syndrome?

Answer 12

• Proportionate short stature (often developing only after birth)
• Minor facial dysmorphism, including ocular hypertelorism (a distance between the eyes that is greater than the 95th percentile) and downslanting eyes; webbed neck
• Heart disease (including pulmonary valve stenosis)
• Intellectual development may be delayed, but by adulthood intelligence is normal in ⅔ of patients.

Question 13

What clinical features would help to distinguish noon syndrome from other genetic syndromes?

Answer 13

• Webbed neck
• Pectus excavatum
• Short stature
• Pulmonary stenosis

Question 14

What cardiac abnormality is associated with noonan syndrome?

Answer 14

Pulmonary stenosis

Question 15

What is the cause of Fragile X syndrome?

Answer 15

X-linked dominant disease caused by a CGG trinucleotide repeat expansion in the FMR1 gene (fragile X mental retardation 1 gene) during oogenesis

Question 16

What are the clinical features of Fragile X syndrome?

Answer 16

• 50–200 repeats (premutation): ataxia, primary ovarian insufficiency, tremor
• > 200 repeats (full mutation):
• Intellectual disability of varying severity
• Delayed language development
• Behavioral features: autistic behavior, hyperactivity, anxiety
• Characteristic facial anomalies
• Long and narrow face
• Prominent forehead and jaw
• Large everted ears
• Hypermobile joints
• In men: postpubertal macroorchidism (enlarged testes; rarely occurs prior to puberty)
• Mitral valve prolapse: can lead to mitral regurgitation
• Above-average head circumference
• Focal seizures

Question 17

What clinical features would help distinguish fragile X from other genetic syndromes?

Answer 17

Things disproportionately enlarged combined with LD
* Macrocephaly
* Long face
* Large ears
* Macro-orchidism