22q11.2 Deletion Syndrome (DiGeorge Syndrome, Velovardiofacial Syndrome)

What is the incidence of DiGeorge?

1/4000

What is another name for DiGeorge Syndrome?

22q11.2 Deletion Syndrome Velocardiofacial Syndrome

What is the recurrence risk for DiGeroge?

<1% is deletion is de novo in child 50% is a parent carries the deletion

What is the inheritance pattern of DiGeorge?

chromosomal (microdeletion) ~10% inherited from parent

What congenital heart diseases are associated with Di George?

conotruncal malformations (tetralogy of fallot, interrupted aortic arch, truncus arteriosis)

What features are commonly associated with DiGeorge?

facial - prom nose, squared nasal root, small eyes, small ears with multiple helices cognitive - IQ in low 70s palatal - velopharyngeal incompetence, submucosal/overt cleft palate endocrine - hypoparathyroidism (hypocalcemia, seizures), GH deficiency, hypo/hyperparathyroidism CV - conotruncal malformations (tetraology of fallot, interrupted aortic arch, truncus arteriosis) immune - impaired T cell production

What endocrine issues are associated with DiGeorge?

hypoparathyroidism (hypocalcemia leading to seizures) GH deficiency hypo/hyperthyroidism

What immune deficiency is associated with DiGeorge?

impaired T cell production from thymic hypoplasia

What are the cognitive features of DiGeorge?

intellectual disability ranging from normal intelligence to moderate disability mean IQ in low 70s

What are the facial features of DiGeorge?

prominent nose squared nasal root small eyes small ears with overfolded helices malar flatness

What is the medical management issues with DiGeorge?

serum ionized calcium concentration parathyroid hormone TSH CBC with differential immune evaluation ophthalmology audiology renal ultrasound baseline cardiac exam CXR for thoracic vertebral anomalies cervical spine films clinical evaluation of palate

What is kind of expressivity is seen in DiGeorge Syndrome?

variable

What palatal abnormalities are associated with DiGeorge?

velopharyngeal incompetence, submucosal cleft palate, overt cleft palate

Can DiGeorge be diagnosed prenatally?

yes with cells from CVS or amniocentesis

What are some of the mutations in DiGeorge?

~85% have 3 Mb deletion ~15% have atypical nested deletions within 22q11.2 1% have chromosome rearrangements involving 22q11.2

How is DiGeorge diagnosed?

FISH for 22q11.2 deletion microarray