Microdeletion syndromes

Of the more than 20 different microdeletion
syndromes (for review see Spinner and
Emanuel, 1996; Budarf and Emanuel, 1997)
three are presented here. The Williams–Beuren
syndrome (1, McKusick 194050, 130160) usually
presents with characteristic facial features
(“elfinlike”), infantile hypercalcemia, supravalvular
aortic stenosis, growth retardation,
and impaired mental development. The underlying
deletion involves the long arm of chromosome
7 at q11.23. The gene for elastin (ELN) is
lost most frequently. Deletion of 22q11 leads to
a group of clinically different but overlapping
disorders (DiGeorge syndrome, McKusick
188400), characterized by absence or hypoplasia
of the thymus and the parathyroid glands
and malformations of the aortic arch; velocardiofacial
syndrome, McKusick 192430; conotruncal
cardiac defects, McKusick 217095; and
others (2). The Rubinstein–Taybi syndrome
(McKusick 180849) is characterized by typical
facial features (3), broad thumbs and toes, and
their associated radiological changes, mental
retardation, and other features. A deletion of
16p13.3 is detectable in about 12% of patients.
Point mutations in the CREB-binding gene (CBP
gene) cause this disorder.