Mosaic ring chromosome 3 in a child with epilepsy and developmental delay

Aims: Report of a girl with severe mental retardation, epilepsy, dysmorphisms and evidence of mosaic ring chromosome 3. Until now there is no other case report with this aberration in literature and databases.

Methods: Case report

Results: Report of a 7 year-old girl with severe mental retardation, microcephaly, nearly absence of expressive speech, epilepsy and minor facial dysmorphisms including the absence of incisors. The epilepsy is characterized by abscences and focal-complex seizures as well as nearly continuous discharges during NREM sleep. In polysomnography criteria for CSWS are not fulfilled (<85% of continuous discharges), intact sleep architecture.

Because of sideeffects switch of the antiepileptic medication with valproat, to ethosuximid and a nocturnal dosage of clobazam.

The diagnostic workup revealed a normal MRI-scan of the brain, there was no evidence of metabolic disorder and no neurotransmitters or glucose transporter deficiency.

Conventional and molecular chromosome analysis (high resolution arrayCGH) on blood lymphocytes did not reveal a causal aberration. Chromosome count on cultured fibroblasts showed mosaicism of a normal cell line and cell lines with one or two supernumerary ring chromosomes. Array analysis delineated a mosaic dosage gain encompassing 35.1 Mb in the chromosomal region 3p14.2 to 3q11.2. The region includes more than 70 genes, some of them supposed to play a role in developmental processes.

Conclusion: Genotype-phenotype correlations of the affected chromosomal region using existing databases and publications did not reveal an identical patient, but size, genomic region and gene content suggest a causal role of the aberration. We hypothesize that the cell line with the supernumerary ring chromosome 3 contributes to the patients phenotype.

ring chromosome - epilepsy - dysmorphism - developmental delay