DiGeorge Syndrome (22q11.2 Deletion Syndrome)

Question 1

What is the inheritance pattern of 22q11?

Answer 1

Sporadic usu.

Dominant inheritance

Question 2

What genetic testing should be ordered for qq211?

Answer 2

FISH analysis for microdeletion 22q11.2

Test parents before genetic counselling

Question 3

What are the associated medical findings with 22q11?

Answer 3

1. Congenital Heart Defects
   a) TOF
   b) VSD
   c) Interrupted aortic arch
2. Palatal anomalies, velopharyngeal incompetence, submucosal CP, craniosynostosis, facial anomalies
   a) Commonly a long tubular nose with hypoplastic alae nasi, “crumpled
   ears”, hypertelorism, malar hypoplasia
   b) Facial features vary with ethnicity
3. Hypotonia, hypocalcemic seizures
4. Immunodeficiency is common – impaired T cell function
5. Hypoparathyroidism, hypocalcemia, growth hormone deficiency
6. ~30% have renal anomalies
7. Early feeding problems
   a) Secondary to cardiac anomalies/palatal defects
   b) Nasal regurgitation
   c) Pharyngeal hypotonia
8. Vomiting, chronic constipation
9. Chronic otitis media and chronic sinusitis
   a) CHL > SNHL
10. Polydactyly, clubfoot, vertebral anomalies
11. Ophthalmologic abnormalities – strabismus; posterior embryotoxon

Question 4

What are the developmental outcomes associated with 22q11?

Answer 4

1. > 90% have developmental disability
2. 20% have autism
3. Communication disorder
   a) Delayed speech
   b) Severe hypernasality leads to poor articulation and atypical pattern of
   language development
   c) May appear apraxic or dyspraxic
4. Increased psychiatric disorders
   a) Bipolar, schizophrenia, mood disorders

Question 5

What is the DDx for 22q11?

Answer 5

1. Cayler Cardiofacial Syndrome (asymmetric crying facies +conotruncal cardiac
   malformation): also 22q11.2 deletion
2. CHARGE Syndrome also features congenital heart disease, immunodeficiency,
   hypocalcemia, and hearing loss.
3. Some overlap with oculo-auriculo-vertebral spectrum
4. (Goldenhar Syndrome), Kabuki Syndrome, Alagille Syndrome

Question 6

What are the recommendations for 22q11?

Answer 6

1. Cardiology evaluation
2. Endocrine evaluation
   o Calcium, hypoparathyroid studies
3. Renal ultrasound
4. Developmental evaluation
5. Early referral for Speech Therapy
6. Monitor for Hearing Loss
7. Immunology evaluation

Question 7

What are the major clinical manifestations for DiGeorge Syndrome?

Answer 7

CATCH-22
C = Congenital heart disease (cotruncal abnormalities, outflow tract abnormalities, interrupted aortic arch, TOF, pulmonary atresia, VSD)
A = Abnormal facies
T = Thymic aplasia (T cell immunodeficiency)
C = Cleft palate +/- lip
H = Hypocalcemia and parathyroid hypoplasia = seizures and tetany
22 = 22q11 deletion