Familial 5q12.3 Microdeletion: Evidence for a Locus Associated with Epilepsy

Abstract

The clinical use of array comparative genomic hybridization (array CGH) has allowed the identification of very rare deletion and duplication disorders, such as 5q12 deletion syndrome (OMIM 615668) described as a contiguous gene deletion syndrome of chromosome 5q12. Chromosome microdeletions including band 5q12 have rarely been reported and have been associated with different phenotypes showing postnatal growth restriction, intellectual disability, epileptic seizures, hyperactivity, and ocular abnormalities. In this study, we describe a family in which array-CGH analysis revealed the presence of an interstitial microdeletion spanning approximately 2.9 Mb in the 5q12 region. The microdeletion is associated with epilepsy in the father and 2 siblings (a boy and a girl). So far, this is the first report in which a familial microdeletion 5q12 manifests in epilepsy. We suggest that this familial microdeletion could delineate a locus for susceptibility to epilepsy.

Cytogenetic and Array-CGH Characterization of a Simple Case of Reciprocal t(3;10) Translocation Reveals a Hidden Deletion at 5q12

“…Previous reports have shown that the 5q12 deletions are associated with a wide range of clinical characteristics, such as postnatal growth retardation, intellectual disability, developmental delay, hyperactivity, nonspecific ocular defects, facial dysmorphism, and, epilepsy [2][3][4][5][6] (Table 2). The size of 5q12 heterozygous deletions varies considerably between 0.9 and 17.2 Mb, and they all occurred de novo, except for the 2.8 Mb inherited deletion associated with epilepsy reported by Gnan and colleagues [6] (Figure 3). In contrast to previous reports, our patient exhibits only modest growth retardation, an angioma of the right lower eyelid, and an ovarian cyst.…”

“…These patients have overlapping clinical features making it difficult to delineate a specific clinical phenotype mainly due to the variable size of the deleted segments between 0.9 to 17.2 Mb. Clinical features range from postnatal growth retardation, intellectual disability, behavioral abnormalities (hyperactivity), nonspecific ocular defects, facial dysmorphism, and epilepsy [2][3][4][5][6]. Here, we report the case of a child from non-consanguineous and healthy parents, which came to our attention for postnatal growth retardation.…”

“…The 5q12 deletion syndrome (OMIM 615668) is a very rare congenital disorder involving a contiguous interstitial gene deletion of chromosome 5q12 region. To our knowledge, deletions of chromosome 5q12 have been reported in nine patients so far [2][3][4][5][6]. These patients have overlapping clinical features making it difficult to delineate a specific clinical phenotype mainly due to the variable size of the deleted segments between 0.9 to 17.2 Mb.…”

A Child with 5q Deletion and Accompanying Chiari 1 Malformation

“…However, Chiari 1 malformation has been reported for the first time in our case. Some genes that are included in the deleted region are known to be expressed in the CNS and that could potentially cause the anomalies [5]. More studies are needed to demonstrate the effects of the other genes in 5q11.…”