A novel syndrome of cerebral cavernous malformation and Greig cephalopolysyndactyly. Laboratory investigation.

Abstract:

OBJECT:Greig cephalopolysyndactyly syndrome (GCPS) is one of a spectrum of overlapping clinical syndromes resulting from mutations in the gene GLI3 on chromosome 7p. Cerebral cavernous malformation (CCM) is caused by mutations in three distinct genes, including Malcavernin (CCM2), which also maps to chromosome 7p and is located 2.8 Mbp from GLI3. The authors describe a new syndrome that combines the vascular lesions characteristic of CCM with the hallmarks of GCPS, including polydactyly, hypertelorism, and developmental delay. METHODS:The authors used high-resolution array-based comparative genome hybridization (CGH) analysis to characterize the 3 million-bp deletion on chromosome 7 that accounts for this novel clinical presentation. A 4-year-old girl presented with polydactyly, hypertelorism, and developmental delay and was also found to have multiple CCMs after suffering a seizure. RESULTS. Genetic analysis using array-based CGH revealed a deletion affecting multiple genes in the 7p14-13 locus, the interval that includes both CCM2 and GLI3. Quantitative real-time polymerase chain reaction (RT-PCR) on genomic DNA confirmed this genomic lesion. CONCLUSIONS:A novel syndrome, combining features of CCM and GCPS, can be added to the group of entities that result from deleterious genetic variants involving GLI3, including GCPS, acrocallosal syndrome, Pallister-Hall syndrome, and contiguous gene syndrome. The deletion responsible for this new entity can be easily detected using either array-based chromosomal analysis or quantitative RT-PCR.

journal_name

J Neurosurg

journal_title

Journal of neurosurgery

authors

Bilguvar K,Bydon M,Bayrakli F,Ercan-Sencicek AG,Bayri Y,Mason C,DiLuna ML,Seashore M,Bronen R,Lifton RP,State M,Gunel M

doi

10.3171/PED-07/12/495

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

495-9

issue

6 Suppl

eissn

0022-3085

issn

1933-0693

journal_volume

107

pub_type

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