MASA (mental retardation, aphasia, shuffling gait, adducted thumbs): Intronic mutation of L1CAM gene in male twins

Introduction: Different mutations of the L1CAM gene are known to produce different clinical phenotypes as X-linked hydrocephalus, MASA syndrome, X-recessive spastic paraplegia and X-recessive agenesis of the corpus callosum with random genotype phenotype correlation. The diagnosis is confirmed by direct sequencing of the coding exons and the flanking intronic regions of the L1CAM gene.

Case history: Male twins were born in the 35th gestational week to a young healthy unrelated couple. Adducted thumbs were recognized in both soon after birth. Agenesis of the corpus callosum was detected by ultrasound in both twins. Psychomotor developmental delay and dystonic movements were present from early age onward. At the age of seven years the boys were severely retarded with poor speech and a peculiar shuffling gait. Handfunction was impaired by the adducted thumbs and was a diagnostic clue to further investigations. Mutation analysis of the L1CAM gene was performed but no mutation could be detected by sequencing of all exons. By applying different primers an intronic mutation IVS27–12G → A could be detected in a hemizygote state in the boys and heterozygote state in their mother (carrier).

Conclusions: Within the expanding phenotypical spectrum of L1CAM gene mutations MASA syndrome is a well defined entity. In the presence of highly suggestive clinical symptoms but negative sequencing of the L1CAM gene, molecular analysis should be extended to intronic regions of the L1CAM gene. The intronic mutation IVS27–12G → A detected in our patients has been recorded 1995 by Jouet et. al. with a very similar clinical phenotype