DiGeorge, Cat Eye, Velocardiofacial Syndromes

 

DIGEORGE, CAT EYE, VELOCARDIOFACIAL SYNDROMES

The P250 probemix is the “high density” 22q11 probemix that has been described by Jalali et al. (2008, Hum Mutat. 29:433-440). The older P023 DiGeorge probemix containing less 22q11 probes is available on request.

 

Microdeletions/-duplications in the 22q11 region cause a variety of disorders, including DiGeorge syndrome (DGS; MIM 188400), velocardiofacial syndrome (VCFS; MIM 192430) and cat eye syndrome (CES; MIM 115470). DGS and VCFS have a large clinical overlap and are both caused by deletions of a specific 1-3 Mb region on chromosome 22q11. The overall birth prevalence of 22q11 deletions appears to be approximately 1 in 4,000, with 75% of these patients having cardiac abnormalities.

 

Cat eye syndrome (CES) has a large phenotypic variability, ranging from near normal to severe malformations. The eyes are predominately affected. CES is caused by the presence of an extra 22q11 copy, usually present as a small extra chromosome, frequently having two centromeres.

 

Although 90% of cases of DGS appear to be due to a 22q11 deletion, other chromosome defects with features of DiGeorge anomaly have also been described. This P250 MLPA probemix further contains probes for several of these regions including 4q35, 8p23, 9q34, 10p14 (DGS2), 17p13 and 22q13. Please inform us when a deletion of one or more of the probes outside the 22q11 region is detected in a patient with a DiGeorge phenotype.

 

The high frequency of 22q11 copy number changes is due to the presence of several copies of a repeat sequence (LCR22). The extent of the 22q11 deletions is variable, although 87% extends from the first (LCR22-A) until the fourth (LCR22-D) repeat. This P250 probemix contains 29 different probes in the 22q11 region and can be used to distinguish the most common types of deletion. Five of these 29 probes are in the cat eye syndrome region and 14 are in the most common DiGeorge deletion.

 

WARNING: The extra chromosome present in cat eye syndrome patients is easily lost during postzygotic divisions, resulting in mosaicism. Detection of CES in mosaic samples might be better done by standard karyotype analysis or by FISH. MLPA measures the average copy number of the CES region and may not be able to detect CES in mosaic samples that contain predominantly normal cells.