Differential Diagnosis

Differential Diagnosis

For current information on availability of genetic testing for disorders included in this section, see GeneTests Laboratory Directory. —ED.

Each of the anomalies seen in the 22q11.2 deletion syndrome can be found as an isolated anomaly in an otherwise normal individual.

Up to 8% of individuals with an isolated palatal cleft, including submucosal cleft, may have deletion 22q11.2, making this the most common genetic syndrome associated with palatal clefts. Conversely, the 22q11.2 deletion syndrome is the most common genetic basis of congenital velopharyngeal incompetence.

Disorders with overlapping features:

  • Smith-Lemli-Opitz syndrome (when polydactyly and cleft palate are present). Smith-Lemli-Opitz syndrome is associated with elevated serum concentration of 7-dehydrocholesterol (7-DHC) or an elevated 7-dehydrocholesterol:cholesterol ratio. Molecular genetic testing for mutations of the DHCR7 gene is available.
  • Alagille syndrome (when butterfly vertebrae, congenital heart disease, and posterior embryotoxon are present). Sequence analysis of the JAG1 gene detects mutations in more than 70% of individuals who meet clinical diagnostic criteria. FISH detects a microdeletion of 20p12, including the entire JAG1 gene, in approximately 5-7% of affected individuals.
  • VATER syndrome (when heart disease, vertebral, renal, and limb anomalies are present)
  • Oculo-auriculo vertebral (Goldenhar) syndrome (when ear anomalies, vertebral defects, heart disease, renal anomalies are present)

Individuals suspected of having the 22q11.2 deletion syndrome but having normal FISH studies may have a chromosome abnormality involving some other chromosomal region, including deletion 10p13-p14.

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