Biology Reference
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the deletion may frequently be missed upon standard cytogenetic analysis.
Shapira et al. (1997) estimate its incidence at more than 1 in 1,000, which
would make 1p36 deletions one of the more common cytogenetic deletion
syndromes. The physical findings in this syndrome can be somewhat vague
and variable, depending on the size of the deletion. Hypotonia, moderate
mental retardation, mild facial dysmorphism, abusive behavior, and hearing
loss are all part of the spectrum of physical findings. Interestingly, a prepon-
derance of maternally derived deletions has been observed (Wu et al. 1999).
By studying a series of deletions of various sizes, Wu et al. (1999) describe
the smallest deletion in which sensorineural hearing loss is present.
2.2.3.2 DiGeorge Syndrome/Velocardiofacial Syndrome
DiGeorge syndrome/velocardiofacial syndrome (DGS1/VCFS) was origi-
nally thought to be two separate entities until both were found to be caused
by deletions in 22q11. Thus, they are now viewed collectively with variable
phenotypes, depending on the deletion size and genetic background. Ninety
percent of deletions occur
de novo
(Gardner and Sutherland 1996). Clini-
cal findings include thymus deficiency, conotruncal heart anomalies, mildly
dysmorphic facies, hypoparathyroidism, palatal anomalies and deaf-
ness (Hong 1998). Heart disease is the leading cause of death among
DGS1/VCFS infants. The phenotype may be highly variable, and members
of the same family, presumably with identical deletions, have variable
expressivity of DGS1/VCFS features (Gardner and Sutherland 1996). The
majority of patients are growth delayed, and most also experience learning
disabilities (Gorlin et al. 1995). The underlying embryological defect is
thought to be improper development of the facial neural crest tissues,
resulting in defective neural pouch derivatives (Lammer and Opitz 1986).
Cytogenetic analysis of DGS1/VCFS individuals reveals a deletion on
one chromosome 22 at band q11 in approximately 33% of cases (Fig. 5.7B).
Often the deletion is cryptic, being so small that it can only be observed
with molecular probes. By molecular studies, at least 90% of DGS1/VCFS
patients have been found to have deletions.
The hearing loss seen in DGS1/VCFS can range from mild to severe and
is usually conductive, though it can be sensorineural. Defects detected are
often structural, owing to interference of development of the 3
rd
and 4
th
pharyngeal pouches (Ohtani and Schuknecht 1984). Mondini deformity is
found, as well as malformed ossicles, and external auditory canal anomalies.
An additional DGS2/VCFS deletion locus is located on 10p. It has been
found
de novo
as an interstitial or terminal deletion of 10p (Fig. 5.7B)
(Schuffenhauer et al. 1998), or as the result of an inherited, unbalanced
translocation (Hon et al. 1995). In addition to the spectrum of features
found in DGS1/VCFS patients with the 22q11 deletion, patients with the
10p deletion can also demonstrate microcephaly, hand and foot anomalies,
genitourinary defects, severe psychomotor retardation and sensorineural
deafness (Shapira et al. 1994). Similar to individuals with 22q11 deletions,
