Online Mendelian Inheritance in Man (OMIM) (original) (raw)

256710

ELEJALDE NEUROECTODERMAL MELANOLYSOSOMAL SYNDROME

Alternative titles; symbols

ELEJALDE SYNDROME

SNOMEDCT: 720417003; ORPHA: 33445;

TEXT

Description

Elejalde neuroectodermal melanolysosomal syndrome is a rare autosomal recessive disorder characterized by silvery-gray hair and severe dysfunction of the central nervous system, present from infancy or early childhood and consisting of severe hypotonia, seizures, and impaired intellectual development. Skin may be hypopigmented with bronzing after sun exposure. Microscopy of hair reveals large granules of melanin unevenly distributed in the hair shaft. Abnormal melanocytes and melanosomes and abnormal inclusion bodies in fibroblasts may be present (Elejalde et al., 1979; Duran-McKinster et al., 1999).

It has been proposed that, in at least some cases, Elejalde neuroectodermal melanolysosomal syndrome and Griscelli syndrome type 1 (GS1; 214450) represent the same entity; see below. 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, reduced or absent 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. Elejalde et al. (1979) extended the observation to 3 sibships who shared common ancestors. The authors noted similarities to Chediak-Higashi syndrome (214500) and Cross oculocerebral syndrome (257800).

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.

Relationship to Griscelli Syndrome

Sanal et al. (2000) referred to neuroectodermal melanolysosomal disease as an allelic variant of Griscelli syndrome. They stated that the patient described in their report had neurologic findings, namely, severe hypotonia and mental-motor retardation from the neonatal period, that were more suggestive of Elejalde syndrome as described by Elejalde et al. (1979) than of the original reports of Griscelli syndrome, with neurologic features associated with infection-induced acute macrophage activation syndrome (i.e., GS2, 607624). This patient had previously been reported by Pastural et al. (1997) (patient 3), who classified the phenotype as Griscelli syndrome but who noted the neurologic similarities to the patients of Elejalde et al. (1979). The patient carried a homozygous mutation in the MYO5A gene (160777.0002).

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.

REFERENCES

  1. Afifi, H. H., Zaki, M. S., El-Kamah, G. Y., El-Darouti, M.Elejalde syndrome: clinical and histopathological findings in an Egyptian male. Genet. Counsel. 18: 179-188, 2007. [PubMed: 17710870]
  2. Anikster, Y., Huizing, M., Anderson, P. D., Fitzpatrick, D. L., Klar, A., Gross-Kieselstein, E., Berkun, Y., Shazberg, G., Gahl, W. A., Hurvitz, H.Evidence that Griscelli syndrome with neurological involvement is caused by mutations in RAB27A, not MYO5A. Am. J. Hum. Genet. 71: 407-414, 2002. Note: Erratum: Am. J. Hum. Genet. 71: 1007 only, 2002. [PubMed: 12058346] [Full Text: https://doi.org/10.1086/341606\]
  3. Bahadoran, P., Ballotti, R., Ortonne, J.-P.Hypomelanosis, immunity, central nervous system: no more 'and,' not the end. Am. J. Med. Genet. 116A: 334-337, 2003. [PubMed: 12522786] [Full Text: https://doi.org/10.1002/ajmg.a.10066\]
  4. Bahadoran, P., Ortonne, J.-P., Ballotti, R., de Saint-Basile, G.Comment on Elejalde syndrome and relationship with Griscelli syndrome. Am. J. Med. Genet. 116A: 408-409, 2003. [PubMed: 12522801] [Full Text: https://doi.org/10.1002/ajmg.a.10065\]
  5. Duran-McKinster, C., Rodriguez-Jurado, R., Ridaura, C., de la Luz Orozco-Covarrubias, M. A., Tamayo, L., Ruiz-Maldonando, R.Elejalde syndrome--a melanolysosomal neurocutaneous syndrome: clinical and morphological findings in 7 patients. Arch. Derm. 135: 182-186, 1999. [PubMed: 10052404] [Full Text: https://doi.org/10.1001/archderm.135.2.182\]
  6. Elejalde, B. R., Holguin, J., Valencia, A., Gilbert, E. F., Molina, J., Marin, G., Arango, L. A.Mutations affecting pigmentation in man: I. Neuroectodermal melanolysosomal disease. Am. J. Med. Genet. 3: 65-80, 1979. [PubMed: 474620] [Full Text: https://doi.org/10.1002/ajmg.1320030112\]
  7. Elejalde, B. R., Valencia, A., Gilbert, E. F., Marin, G., Molina, J., Holguin, J.Neuro-ectodermal melanolysosomal disease: an autosomal recessive pigment mutation in man. (Abstract) Am. J. Hum. Genet. 29: 39A only, 1977.
  8. Huizing, M., Anikster, Y., Gahl, W. A.Reply to Menasche et al. (Letter) Am. J. Hum. Genet. 71: 1238 only, 2002.
  9. Ivanovich, J., Mallory, S., Storer, T., Ciske, D., Hing, A.12-year-old male with Elejalde syndrome (neuroectodermal melanolysosomal disease). Am. J. Med. Genet. 98: 313-316, 2001. [PubMed: 11170073] [Full Text: https://doi.org/10.1002/1096-8628(20010201)98:4<313::aid-ajmg1098>3.0.co;2-p]
  10. Menasche, G., Fischer, A., de Saint Basile, G.Griscelli syndrome types 1 and 2. Am. J. Hum. Genet. 71: 1237-1238, 2002. [PubMed: 12452176] [Full Text: https://doi.org/10.1086/344140\]
  11. Pastural, E., Barrat, F. J., Dufourcq-Lagelouse, R., Certain, S., Sanal, O., Jabado, N., Seger, R., Griscelli, C., Fischer, A., de Saint Basile, G.Griscelli disease maps to chromosome 15q21 and is associated with mutations in the myosin-Va gene. Nature Genet. 16: 289-292, 1997. Note: Erratum: Nature Genet. 23: 373 only, 1999. [PubMed: 9207796] [Full Text: https://doi.org/10.1038/ng0797-289\]
  12. Sanal, O., Yel, L., Kucukali, T., Gilbert-Barnes, E., Tardieu, M., Texcan, I., Ersoy, F., Metin, A., de Saint Basile, G.An allelic variant of Griscelli disease: presentation with severe hypotonia, mental-motor retardation, and hypopigmentation consistent with Elejalde syndrome (neuroectodermal melanolysosomal disorder). J. Neurol. 247: 570-572, 2000. [PubMed: 10993506] [Full Text: https://doi.org/10.1007/s004150070162\]

Contributors:

Anne M. Stumpf - updated : 05/18/2022
Cassandra L. Kniffin - updated : 9/14/2007
Anne M. Stumpf - updated : 3/14/2003
Victor A. McKusick - updated : 12/23/2002
Victor A. McKusick - updated : 9/24/2002
Victor A. McKusick - updated : 8/20/2002
Sonja A. Rasmussen - updated : 3/13/2001
Victor A. McKusick - updated : 4/28/1999

Creation Date:

Victor A. McKusick : 6/4/1986

Edit History:

alopez : 05/19/2022
alopez : 05/18/2022
carol : 05/25/2010
carol : 1/23/2009
wwang : 9/24/2007
ckniffin : 9/14/2007
ckniffin : 12/15/2006
tkritzer : 1/13/2004
alopez : 3/18/2003
alopez : 3/14/2003
alopez : 3/14/2003
terry : 12/23/2002
tkritzer : 9/24/2002
tkritzer : 9/24/2002
alopez : 8/23/2002
tkritzer : 8/22/2002
terry : 8/20/2002
terry : 3/26/2001
mcapotos : 3/13/2001
alopez : 5/10/1999
terry : 4/28/1999
mimadm : 3/11/1994
supermim : 3/17/1992
supermim : 3/20/1990
ddp : 10/27/1989
root : 1/23/1989
marie : 3/25/1988