Chromosomal instabilities

Question 1

[Gen/Chr instability/CdLS]

Facial characteristics of Cornelia de Lange syndrome? (4)

Answer 1

1. Downturned mouth, thin upper lip
2. Micrognathia
3. Low hairline
4. Synophrys (eyebrow fusion), long eyelashes

Question 2

[Gen/Chr instability/CdLS]

Body characteristics of Cornelia de Lange syndrome? (4)

Answer 2

1. Microbrachycephaly (small, flat head)
2. Micromelia (small hands/feet),
3. Phocomelia (hands/feet closely attached to the body)
4. 2/3 Syndactyly of toes

Question 3

[Gen/Chr instability/CdLS]

Developmental/Neurological symptoms of Cornelia de Lange syndrome? (4)

Answer 3

1. Intrauterine growth restriction, poor growth
2. Microcephaly
3. Intellectual disability, autism, behavioral issues
4. Hearing loss

Question 4

[Gen/Chr instability/CdLS]

Anomalies other than neurologic of Cornelia de Lange syndrome? (4)

Answer 4

1. Eye: Myopia
2. GI: GI reflux
3. Heart: Cardiac defects
4. GU: Renal anomalies, genital anomalies

Question 5

[Gen/Chr instability/SRS]

Genetic causes of Silver-Russell syndrome? (2)

Answer 5

1. Hypomethylation of imprinting control region 1 (ICR1) at 11p15.5 (35-50%)
2. Maternal uniparental disomy (7-10%)

Question 6

[Gen/Chr instability/SRS]

Characteristics of Silver-Russell syndrome? (4)

Answer 6

1. Pre/post-natal low weight and height (normal HC)
2. Delayed bone age
3. GI reflux
4. Cafe au lait spots

Question 7

[Gen/Chr instability/AT]

Causal gene for ataxia-talengiectasia?

Answer 7

ATM gene
(Autosomal recessive)

Question 8

[Gen/Chr instability/AT]

Classic ataxia-talengiectasia neurologic features? (3)

Answer 8

1. progressive cerebellar ataxia (ages 1-4 years)
2. oculomotor apraxia
3. choreoathetosis

Question 9

[Gen/Chr instability/AT]

Classic ataxia-talengiectasia other than neurologic features? (3)

Answer 9

1. Telangiectasias of the conjunctivae
2. Immunodeficiency, frequent infections (sinopulmonary, bronchiectasis)
3. An increased risk for malignancy, particularly leukemia and lymphoma

Question 10

[Gen/Chr instability]

Name of syndrome?

With ataxia, frequent infection, malignancies

Answer 10

Ataxia telangiectasia

Question 11

[Gen/Chr instability/Fanconi]

Physical features of Fanconi anemia? (5)

Answer 11

1. Cafe au lait, hypopigmentation
2. Hypoplastic thumb and radius
3. microcephaly, short stature
4. ophthalmic anomalies
5. genitourinary tract anomalies

Question 12

[Gen/Chr instability/XP]

Characteristics of Xeroderma pigmentosum? (3)

Answer 12

1. Acute sun sensitivity: severe sunburn with blistering, persistent erythema on minimal sun exposure with marked freckle-like pigmentation of the face before age two years
2. Sunlight-induced ocular involvement: photophobia, severe keratitis, atrophy of the skin of the lids, ocular surface neoplasms
3. Greatly increased risk of sunlight-induced cutaneous neoplasms

Question 13

[Gen/Chr instability/Bloom]

Clinical features of Bloom syndrome? (5)

Answer 13

1. Pre- and postnatal growth deficiency
2. Immune abnormalities
3. Sensitivity to sunlight
4. Insulin resistance
5. High risk for cancers
   (normal intellectual ability)