Griscelli Syndrome Type 1 (GS with Neurological Involvement)

Clinical Features and Genetic Patterns

GS1 (OMIM #214450) represents hypomelanosis with a primary neurological deficit and without immunologic impairment or manifestations of hemophagocytic syndrome.

Neuromuscular disorders are the hallmark of the disease. Psychomotor impairment may have two forms of presentation: congenital or infantile, first developing during childhood.

The sudden presentation of central nervous system dysfunction can be compared with the accelerated phase described in Chediak-Higashi syndrome Opens in new window and GS2 Opens in new window. A severe regressive psychomotor process develops rapidly with loss of normal skills until patients die.

A triggering factor for this sudden dysfunction has not yet been identified. Severe migraine status followed by hemiparesis has also been described.

In general, normal humoral and cellular immunity is observed and recurrent infections are not the rule as in Chediak-Higashi syndrome (CHS) Opens in new window and GS3 Opens in new window.

Ocular abnormalities are quite frequent. Patients may present congenital amaurosis or progressive loss of vision, nystagmus, diplopia as well as hypopigmented retina.

Death usually occur within the first decade of life when the patients are not treated.

Cause: Gene Description

GS1 is caused by mutations in the gene encoding myosin Va (or myosin 5a) (MYO5A) located on chromosome 15q21.

MYO5A is a motor molecule, one of the large family of unconventional class myosin V, involved in melanosome movement as well as neurosecretory vesicles.

Mutation in MYO5A has been found in synaptic terminals in the retina and brain.

It is required for normal photoreceptor signaling, suggesting that it might function in central nervous system synapses in general, with aberrant synaptic activity.

Bahadoran et al. (2003a, b) characterized GS1 as comprising hypomelanosis and severe central nervous system dysfunction, corresponding to the dilute phenotype in the mouse.

Some authors suggested that Elejalde syndrome Opens in new window and GS1 may represent allelic conditions or (at least) in some patients the same entity.

Sanal et al. (2000) suggested that ashen is a mouse model of Elejalde syndrome Opens in new window: however, in 2000 Wilson et al. showed that a mutated Rab27a gene, not the MYOVA gene, causes the pathology of Mouse.

Anikster et al. (2002) suggested also that neurological involvement in some patients with GS occurred secondarily to the hemophagocytic syndrome and that patient with primary central nervous system complications and MYOVA mutations (i.e., with the GS1 form) have Elejalde syndrome Opens in new window.

Several other reports established that neurological manifestations in patients with GS caused by RAB27A (i.e., the GS2 form) were related to lymphocyte infiltration of the central nervous system, whereas patients with GS caused by MYO5A mutations (i.e., the GS1 form) exhibited a primary neurological disease potentially described as Elejalde syndrome Opens in new window.

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