Digeorge Syndrome, Takao Syndrome, Shprintzen syndrome (velocardiofacial)
The infant described in the vignette has a number of features of DiGeorge
syndrome. DiGeorge syndrome results from abnormal cervical neural crest
migration into the derivatives of the third and fourth pharyngeal arches and
pouches during early embryogenesis. The pattern of malformations includes
hypoplasia
or aplasia
of the thymus and parathyroid glands and structural abnormalities of the great
vessels. The defects lead to the classic clinical manifestations of
deficient
cellular immunity due to T-cell dysfunction, causing increased
susceptibility to infection;
hypocalcemia due to absent
parathyroid hormone, resulting in hypocalcemic
seizures; and aortic
arch abnormalities. Some affected infants also have facial
dysmorphic features, which can
include hypertelorism,
short
palpebral
fissures, short philtrum,
micrognathia, and
ear abnormalities.
Most patients who have DiGeorge syndrome are found to have partial monosomy for
the proximal long arm of chromosome 22 due to microdeletion of
22q11.2. This microdeletion can
be detected by fluorescent in situ hybridization (FISH)
using a molecular probe specific for the region. Although the deletion
occasionally is evident on routine chromosome analysis, the FISH study is much
more sensitive. Most cases represent de
novo deletion events, although familial cases have been described.
The 22q11.2 deletion is associated with
a variety of other phenotypes, including the
Shprintzen syndrome (velocardiofacial
syndrome), Takao syndrome, and
isolated outflow tract defects of the
heart (eg, tetralogy of Fallot, truncus arteriosus, interrupted aortic
arch). In general, Takao syndrome is
diagnosed when the patient primarily has cardiac disease,
with normal T-cell and parathyroid function.
Shprintzen (velocardiofacial) syndrome
denotes those patients who have the features of DiGeorge syndrome
plus craniofacial and palatal abnormalities. Of
interest, all three phenotypes can be evident in a single family in which
a heritable chromosome 22 deletion is present. It has been suggested that this
constellation of related syndromes that have the common etiologic factor of a
chromosome 22 deletion should be termed CATCH22 for
Cardiac abnormality, Abnormal
facies,
T-cell deficit, Cleft palate, and
Hypocalcemia
resulting from 22q11 deletion. In general, the diagnosis of
DiGeorge
syndrome requires a neonatal presentation of
thymic
hypoplasia
and hypocalcemia;
Shprintzen
syndrome requires the presence of nasal speech due to palatal
insufficiency.
Because deafness is not a major feature of DiGeorge syndrome, obtaining
brainstem auditory evoked potentials is not indicated. The etiology of the
seizure in the infant described in the vignette is hypocalcemia, and
electroencephalography would not provide additional useful information for
management, which should include administration of calcium. Hypothyroidism
usually is not evident in the newborn period, and thyroid function is preserved
in DiGeorge syndrome.
References:
Burn J, Wilson DI, Cross I, et al. The clinical significance of 22q11
deletion. In: Clark EB, Markwald RR, Takao A, eds. Developmental
Mechanisms of Heart Disease. Armonk, NY: Futura Publishing Co;
1995:559-567
Burn J. Closing time for CATCH22. J Med Genet. 1999;36:737-738
DeSilva D, Duffty P, Booth P, Auchterlonie I, Morrison N, Dean JC.
Family studies in chromosome 22q11 deletion: further demonstration of
phenotypic heterogeneity. Clin Dysmorphol. 1995;4:294-303
Ryan AK, Goodship JA, Wilson DI, et al. Spectrum of clinical features
associated with interstitial chromosome 22q11 deletions: a European
collaborative study. J Med Genet. 1997;34:798-804
Stevens CA, Carey JC, Shigeoka AO. DiGeorge anomaly and
velocardiofacial syndrome. Pediatrics. 1990;85:526-530