Severe mental retardation, seizures, and hypotonia due to deletions of MEF2C

Abstract We present four patients, in whom we identified overlapping deletions in 5q14.3 involving MEF2C using a clinical oligonucleotide array comparative genomic hybridization (CGH) chromosomal microarray analysis (CMA). In case 1, CMA revealed an ∼140 kb deletion encompassing the first three exons of MEF2C in a 3‐year‐old patient with severe psychomotor retardation, periodic tremor, and an abnormal motor pattern with mirror movement of the upper limbs observed during infancy, hypotonia, abnormal EEG, epilepsy, absence of speech, autistic behavior, bruxism, and mild dysmorphic features. MRI of the brain showed mild thinning of the corpus callosum and delay of white matter myelination in the occipital lobes. In case 2, an ∼1.8 Mb deletion of TMEM161B and MEF2C was found in a child with severe developmental delay, hypotonia, and seizures. Patient 3 had epilepsy, hypotonia, thinning of the corpus callosum, and developmental delay associated with a de novo ∼2.4 Mb deletion in 5q14.3 including MEF2C and five other genes. In case 4, a de novo ∼5.7 Mb deletion of MEF2C and five other genes was found in a child with truncal hypotonia, intractable seizures, profound developmental delay, and shortening of the corpus callosum on brain MRI. These deletions further support that haploinsufficiency of MEF2C is responsible for severe mental retardation, seizures, and hypotonia. Our results, in combination with previous reports, imply that exon‐targeted oligo array CGH, which is more efficient in identifying exonic copy number variants, should improve the detection of clinically significant deletions and duplications over arrays with probes spaced evenly throughout the genome. © 2010 Wiley‐Liss, Inc.