Elejalde Disease

A number sign (#) is used with this entry because it has been proposed that neuroectodermal melanolysosomal disease, or Elejalde disease, and Griscelli syndrome type 1 (GS1; 214450) represent the same entity. GS1 is caused by mutation in the MYO5A gene (160777).

Clinical Features

Elejalde et al. (1977) described a novel pigment mutation in 2 males and 1 female, each from a consanguineous marriage in an inbred Colombian kindred. The condition was characterized by profound psychomotor retardation, seizures, hypotonia, voluntary movements, generalized hypopigmentation, and silver-colored hair from early in life. One died at 5.5 years of age of a respiratory infection. In homozygotes, abnormal melanolysosomes were found in melanocytes and keratinocytes of skin, histiocytes of bone marrow, melanocytes of hair bulbs, and cultured fibroblasts. A few abnormal melanolysosomes were found in obligatory heterozygotes. In the bone marrow the abnormal structures were excreted into the extracellular space. A possible relationship to Chediak-Higashi syndrome (214500) was unclear. The phenotype is also reminiscent of the Cross oculocerebral syndrome (257800). Elejalde et al. (1979) extended the observation to 3 sibships who shared common ancestors.

Duran-McKinster et al. (1999) described 7 patients thought to have the melanolysosomal neurocutaneous syndrome described by Elejalde et al. (1979). They referred to the disorder as Elejalde disease. The patients reported by Duran-McKinster et al. (1999) had silvery hair and profound neurologic dysfunction. Immune impairment was not found. The age of onset of neurologic signs ranged from 1 month to 11 years. The signs included severe muscular hypotonia, ocular alterations, and seizures. Mental retardation since the first months of life was noted in 4 cases. Psychomotor development was normal in 3 cases, but suddenly the patients presented with a regressive neurologic process. Four patients died between 6 months and 3 years after the onset of neurologic dysfunction. In addition to the silver-leaden hair, bronze skin developed after sun exposure. Large granules of melanin unevenly distributed in the hair shaft were observed. Duran-McKinster et al. (1999) recommended that the differential diagnosis include Chediak-Higashi syndrome and Griscelli syndrome (214450).

Ivanovich et al. (2001) reported a 12-year-old male with neuroectodermal melanolysosomal disease and compared this condition with Chediak-Higashi and Griscelli syndromes. Their patient had severe developmental delay, seizure activity, exotropia, nystagmus, ataxia, and silvery gray hair and eyebrows. His skin was not hypopigmented but bronzed with diffuse freckling in sun-exposed areas. He had no history of recurrent infections and had normal immunologic studies. The authors suggested that their case may be the oldest living child with this condition reported in the literature.

Afifi et al. (2007) reported a 2-year-old Egyptian boy with Elejalde syndrome, born of consanguineous parents. He had delayed development, seizures, hypotonia, squint, nystagmus, and silvery hair, eyelashes, and eyebrows. He was unable to tolerate hot weather or sun, although sweating was normal and exposed skin tanned easily. Ophthalmologic examination showed intermittent alternating exotropia with mild hypertropia, bilateral optic atrophy, and impaired macular function. EEG showed focal abnormalities, and brain imaging showed cerebellar and cortical atrophy. Histologic analysis of the hair and skin showed irregularly distributed melanin clumps. There were no immunologic abnormalities.

Molecular Genetics

Sanal et al. (2000) referred to neuroectodermal melanolysosomal disease as an allelic variant of Griscelli syndrome.

Anikster et al. (2002) suggested that families previously thought to have Griscelli syndrome due to mutations in the MYO5A gene (160777) may in fact have suffered from Elejalde syndrome, the lack of immunologic defects being an important distinction from Griscelli syndrome (see Griscelli syndrome type 2, 607624). Menasche et al. (2002), Huizing et al. (2002), and Bahadoran et al. (2003, 2003) also suggested the identity of Elejalde syndrome, at least in some patients, and Griscelli syndrome type 1.

Bahadoran et al. (2003) noted that 2 groups of patients with Elejalde syndrome, possibly representing separate entities, were described. In the original description patients showed the characteristic hair shaft melanin granule clumping of Griscelli syndrome, but melanosome transfer to keratinocytes appeared normal, melanocyte maturation appeared abnormal, and inclusion bodies occurred in other cell types. By contrast, the second series of Elejalde syndrome patients (Duran-McKinster et al., 1999; Ivanovich et al., 2001) had clinical and histologic features suggestive of Griscelli syndrome type 1.

Nomenclature

This disorder is distinct from the similarly named Elejalde syndrome (200995), which is also known as acrocephalopolydactylous dysplasia.