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MASA is an acronym for mental retardation, aphasia, shuffling gait, and adducted thumbs. Hydrocephalus associated with aqueductal stenosis. Extremely rare inherited disorder that is one of several disorders known as X-linked mental retardation (XLMR) syndromes.

Clasped Thumb and Mental Retardation Syndrome; Gareis-Mason Syndrome; Spastic Paraplegia Type I Syndrome; Crash Syndrome.

Rare; it is responsible for approximately 10% of cases of hydrocephalus in males.

X-linked recessive; locus at Xq28. Caused by a mutation in the gene for the neural L1 cell adhesion molecule (L1-CAM).

Seems to be associated with a mutation in L1-CAM, which is an axonal glycoprotein that is essential for normal development of the central and peripheral nervous systems during the fetal period and postnatally. However, the exact function of the L1-CAM protein is not fully understood.

Clinical picture; prenatal-onset hydrocephalus in males. Female carriers may have mild mental retardation or slightly adducted thumbs.

Varies from extreme macrocephaly following hydrocephalus caused by in utero stenosis of the sylvian aqueduct to absence of hydrocephalus with mental retardation and aphasia. Shuffling gait secondary to spastic paraplegia. Adducted thumbs (i.e., flexed over the palms or “cortical thumb”). Small stature. Lumbar lordosis.

Risk of raised intracranial pressure should be well assessed. Neurologic and cardiovascular status should be evaluated.

Prevent elevation of intracranial pressure.

Avoid anesthetic agents with known potential to increase intracranial pressure.

X-Linked Hydrocephalus (Bickers Adams Syndrome): Characterized by severe hydrocephalus and caused by congenital stenosis of the aqueduct of Sylvius (HSAS). Other clinical features include macrocephaly, mental retardation, hypoplastic clasped or adducted thumbs, and/or spastic paraplegia. It is inherited as an X-linked recessive pattern. X-linked hydrocephalus and MASA syndrome result from different mutations of the same L1-CAM gene and are considered allelic disorders.

Complicated X-Linked Spastic Paraplegia (SPG1): Characterized by early onset and slow progression of symptoms such as muscle weakness, legs spasticity, mental retardation, optic nerves atrophy, and/or neurodegeneration of certain parts of the brain (e.g., cerebellum, cerebral cortex). It affects primarily males. Other clinical features include ataxia, spastic paraplegia, and hydrocephalus. Complicated X-linked spastic paraplegia (SPG1) and MASA syndrome are thought to result from different mutations of the same gene (allelic disorders) on the X chromosome (L1-CAM).

Uncomplicated X-Linked Spastic Paraplegia (SPG2): Milder form characterized by late onset, severe hyperreflexia, and spastic gait. Nystagmus, optic nerve atrophy, mild intellectual disability, and/or coordination problems are significant features. The genetic mutations that cause this disorder do not occur in the same region of the X chromosome as those occurring in MASA syndrome, X-linked hydrocephalus, and complicated X-linked spastic paraplegia.

Renpenning Syndrome: Affects only males; characterized by moderate-to-severe mental retardation, microcephaly, short stature, and/or microgenitalia. Renpenning type is thought to be inherited as an X-linked recessive genetic trait.

Escalante Syndrome: Similar to ...

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