MECP2 duplication syndrome in a patient from Cameroon

Abstract

MECP2 duplication syndrome (MDS; OMIM 300260) is an X-linked neurodevelopmental disorder caused by nonrecurrent duplications of the Xq28 region involving the gene methyl-CpG-binding protein 2 (MECP2; OMIM 300005). The core phenotype of affected individuals includes infantile hypotonia, severe intellectual disability, very poor-to-absent speech, progressive spasticity, seizures, and recurrent infections. The condition is 100% penetrant in males, with observed variability in phenotypic expression within and between families. Features of MDS in individuals of African descent are not well known. Here, we describe a male patient from Cameroon, with MDS caused by an inherited 610 kb microduplication of Xq28 encompassing the genes MECP2, IRAK1, L1CAM, and SLC6A8. This report supplements the public data on MDS and contributes by highlighting the phenotype of this condition in affected individuals of African descent.

Keywords: MECP2 duplication; Africa; Cameroon; Xq28 duplication; array-CGH.

Figure 1.

Craniofacial features and habitus of the patient. (a) image of the patient at the age of 1year showing a broad face with full checks, high forehead with high anterior hairline and a small open mouth. (b) front view of the face at 5 years showing midface retrusion, depressed nasal bridge and deeply set eyes with infra-orbital folds. (c1), (c2), (c3) facial features at 6 years showing sparse eyebrows, low-set ears, anteverted nares, open mouth with protruded tongue, and thick and everted vermillion of the lower lip. (d) photograph at 8 years of age showing patient’s usual posture with flexion of the trunk and knees. Written informed consent was obtained from the family for publication of these photographs.

Figure 2.

Results of array comparative Genomic Hybridization (array-CGH). Analysis performed on genomic DNA from the patient and his mother showing a duplication with a size of 610kb, spanning the region Xq28 with breakpoints located between positions 152,780,136 and 153,390,314 bp (GRCh37/hg19). The duplication encompasses 21 OMIM protein-coding genes (https://www.genome.ucsc.edu/cgi-bin/hgTables), including MECP2, IRAK1, L1CAM and SLC6A8.