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Incidence

The syndrome is familial and is transmitted as an X-linked trait. The gene encoding is linked to L1 located near the telemere of the long arm of chromsoome X (Xq28). MASA syndrome is inherited as an X-linked recessive genetic trait. Therefore, the disorder is usually fully expressed in males only. However, some females who carry one copy of the gene (heterozygotes) do appear to fully express the disease, while some others may exhibit only some milder symptoms associated with the disorder such as dull intelligence and/or adducted thumbs.

Clinical Characteristics

MASA syndrome is an extremely rare inherited disorder that is one of several disorders known as X-linked mental retardation (XLMR) syndromes. The acronym MASA stands for (M)ental retardation, (A)phasia, a diminished ability to communicate by speech, writing, and/or signs, (S)huffling manner of walking (gait), and (A)dducted thumbs, thumbs that are flexed inward toward the palm. Shuffling gait may be due to impaired control of voluntary movements and progressive rigidity of muscles in the legs (spastic paraplegia). Adduction of the thumbs may be due to absence or underdevelopment (hypoplasia) of certain muscles (extensor pollicis longus and/or brevis muscles) of the hand near the thumb. The symptoms and physical findings associated with MASA syndrome vary greatly from case to case. Affected individuals may not experience all of the main characteristics described above and may exhibit various other symptoms and physical findings such as abnormal dilatation of the ventricles within the brain and hydrocephalus, mild short stature, exaggerated lumbar lordosis, and/or other skeletal abnormalities. According to the medical literature, mental retardation is the only feature that has been present in all documented cases of the disorder. MASA syndrome, X-linked hydrocephalus, and spastic paraplegia (SPG1) share many common characteristics. MASA syndrome (Mental retardation, Aphasia, Shuffling gait, Adductus thumbs) is an X-linked mental retardation syndrome characterized by spasticity of the lower limbs with hyperreflexia, aphasia and adductus thumbs. Brain imaging provides evidence of dilated cerebral ventricles, stenosis of the aqueduct of Sylvius, hypoplasia or agenesis of the corticospinal tract and agenesis of the corpus callosum. The existence of MASA syndrome and spastic paraplegia (SPP) in families with Hydrocephalus due to Stenosis of the Aqueduct of Sylvius (HSAS) lead to the hypothesis that these conditions represent pleiotropic effects of mutations in a single gene, which was confirmed when L1CAM mutations were found in all these conditions. The clinical diagnosis of MASA syndrome may be difficult and detection of L1CAM mutations, although labor-intensive because of the fragmentation of the coding region into 28 exons, of the great allelic heterogeneity, and of the large distribution of the mutations within the coding region, confirms, on a molecular basis, this diagnosis. Furthermore, it allows to refine genetic counseling in affected families. In this view, female carriers have to be detected as they may give birth to children affected with MASA, HSAS or SPP. Finally, the identification of L1CAM mutations allow to carry out prenatal diagnosis in these X-linked mental retardation syndromes.

Precipitants

None

Provocation Tests

None

Diagnostic Procedures

It is a clinical diagnosis. The clinical diagnosis of MASA syndrome may be difficult and detection of L1CAM mutations, although labor-intensive because of the fragmentation of the coding region into 28 exons, of the great allelic heterogeneity, and of the large distribution of the mutations within the coding region, confirms, on a molecular basis, this diagnosis.