Congenital malformations - Edocr

96 PART III CRANIOFACIAL MALFORMATIONS
TABLE 13-3 Clinical Features of 22q11.2 Deletion Syndrome
Findings
% Affected
Congenital heart defects (total) 74%
Tetralogy of Fallot 22%
Interrupted aortic arch 15%
Ventricular septal defect 13%
Truncus arteriosus 7%
Other 17%
Palatal abnormalities (total) 69%
Overt cleft palate 11%
Other 58%
Immune defects 77%
Hypocalcemia 50%
Renal anomalies 37%
Characteristic facial features
Majority
Minor ear anomalies
Prominent nose
Narrow palpebral fissures
Retruded mandible
Flattened malar area
Slender fingers 63%
Feeding problems 30%
Learning problems 90%
syndrome (VCFS). More than 95% of individuals
with typical clinical features of 22q11.2 deletion
will have detectable deletions by FISH testing.
A small number of individuals with the 22q11.2
phenotype have a deletion of chromosome 10p13.
The 22q11.2 deletion syndrome is inherited in
an autosomal dominant fashion. Approximately
90% of affected individuals have a de novo (new)
deletion and 10% have an inherited deletion from
a parent. Offspring of affected individuals have a
50% chance of inheriting the deletion.
The combination of CP (frequently U-shaped),
micrognathia (small mandible), and glossoptosis
(tongue retroposition into the pharyngeal
airway resulting in variable degrees of obstruction
and respiratory distress) was first described
by Pierre Robin in 1923 11 and is referred to as
Pierre Robin syndrome or Robin sequence.
While the classic definition of Robin sequence
requires the presence of all three findings, various
authors have advocated other definitions
allowing for the presence of only two findings,
most commonly micrognathia and CP without
glossoptosis. 12
Robin sequence often occurs as an isolated
condition in otherwise normal individuals, but it
may also occur with additional nonspecific congenital
anomalies or as one feature in more than
40 genetic disorders. 13 In one study, Robin sequence
occurred as an isolated finding in 48% of
cases, with additional anomalies in 17% of cases,
and as part of an identifiable syndrome in 35%
of cases. 14 The most common genetic disorders
associated with Robin sequence are 22q11.2
deletion syndrome, Stickler syndrome, and
Treacher Collins syndrome (see Micrognathia).
Stickler syndrome is an autosomal dominant
connective tissue disorder caused by mutations in
one of the three collagen genes (COL2A1,
COL11A1, and COL11A2). The most common
features include ocular findings (myopia, cataract,
retinal detachment), hearing loss (conductive and