MEF2C mutations are a rare cause of Rett or severe Rett‐like encephalopathies

Fig. 1. Identification of a large rearrangement affecting the MEF2C gene. A deletion affecting exons 4 to 14a was identified by quantitative polymerase chain reaction in a patient presenting with a severe encephalopathy. The patient was born by spontaneous delivery after an uneventful pregnancy. At birth, he was a hyperactive baby. At 8 months, he experienced myoclonic seizures and infantile spasms with an abnormal EEG pattern. Seizures were well controlled before the age of 4 years. The patient was able to walk unaided at 4 years of age. At our last examination at the age of 9 years, he presented with poor eye contact, combined stereotypies, dyskinesias and severe global developmental delay. Head circumference was normal (53 cm, 50th centile). He had a normal muscle tone and presented with recurrent infections. Magnetic resonance imaging data and clinical pictures were not available for this patient. This deletion removes the entire coding sequence (isoform α1, NM_002397.3 corresponding to the longest transcript) and leads to a MEF2C null allele. The distal breakpoint lies within the first intron of MEF2C. The closest proximal coding sequence (LOC645323) is not affected by this deletion in 5q14.3. For each amplicon, we tested 5q14.3 diploid (normal) and haploid (5q14.3 deletion) DNA controls for the quantification. found altered in patients with severe mental retardation (MR), absence of speech, severe hypotonia, epilepsy, stereotypic movements, normal head circumference, absence of regression, and cerebral malformations (1, 2), a phenotype suggestive of the early-onset seizures variant of RTT. According to Zweier and collaborators, 2% of RTT-like disorders might be attributed to