eMedicine Specialties > Dermatology > Diseases of Pigmentation
Elejalde Syndrome
Updated: Feb 12, 2008
Introduction
Background
Elejalde syndrome (ES) was first described in 19771 in 3 consanguineous families in Columbia. The largest series of patients has been reported in Mexico.
Silvery hair and CNS dysfunction characterize this rare autosomal recessive syndrome. The main cutaneous features of ES include silver-leaden (silvery) hair and intense tanning after sun exposure (bronze skin color on sun-exposed areas).
Severe neurologic impairment (eg, seizures, severe hypotonia, mental retardation) either is congenital or develops during childhood. The immune system is not impaired. ES has a wide spectrum of ophthalmologic abnormalities.
Large granules of melanin are unevenly distributed in the hair shaft. Abnormal melanocytes, melanosomes, and abnormal inclusion bodies may be present in fibroblasts. ES must be distinguished from Chédiak-Higashi syndrome and Griscelli syndrome.
ES (Online Mendelian Inheritance in Man [OMIM] entry #2567102 ) should not be confused with another Elejalde syndrome (OMIM entry #200995), also known as acrocephalopolydactylous dysplasia.
Pathophysiology
The pathophysiology of ES is not fully understood. Some have stated that it is the result of a distorted gene product responsible for early melanin formation. The abnormal melanosomes form leaden-to-silvery colored hair and cause defective CNS function.In 2000, Lambert et al3 stated that the neurologic abnormalities seen in ES are probably not caused by abnormal neuromelanin deposition. Instead, Lambert et al posited that the neurologic abnormalities may be linked to impaired function of a molecule playing a common role in melanocytic and neuronal organelle function. Lambert et al believe that the likely candidate genes for ES must be sought in the variety of genes involved in organellogenesis and intracellular trafficking.
In 2000, Sanal et al4 referred to neuroectodermal melanolysosomal disease as an allelic variant of Griscelli syndrome. In 2002, Anikster et al5 suggested that families previously thought to have Griscelli syndrome due to mutations in the MYO5A gene (OMIM entry #160777) may in fact have had ES.
The absence of immunologic defects allows ES to be distinguished from Griscelli syndrome (at least type 1). Sanal et al4 suggest that ashen is a mouse model of ES; however, in 2000, Wilson et al6 showed that a mutated Rab27a gene, not the MYO5A gene, causes the pathology of the ashen mouse. This discussion is summarized from the OMIM page on this disease (see OMIM Elejalde syndrome)2 .
Frequency
United States
ES is extremely rare, with fewer than 20 patients reported.
International
In 1977, Elejalde et al1 described a new pigment mutation in 2 males and 1 female, each from a consanguineous marriage in an inbred Colombian kindred. Whether the disease is more common in Columbia is unknown. The large series of patients with ES is from Mexico, but whether this finding indicates an increased incidence is unknown.
Afifi et al7 reported on an Egyptian male patient with ES who had silvery hair since birth, generalized hypopigmentation, severe primary CNS dysfunction, and normal hematological and immunologic profiles.
Mortality/Morbidity
- Death occurs from neurologic collapse in childhood. One report noted deaths of children aged 3 months to 4 years. Another report8 noted that a patient with ES was alive at age 12 years.
- The main morbidity comes from neurologic dysfunction and psychomotor regression and dysfunction.
- Another report noted that one patient with ES died of respiratory infection at age 5.5 years.
Race
A racial predilection is not known.
Sex
ES is an autosomal recessive disease; therefore, no difference in sexual frequency exists.
Age
This disease usually starts to manifest during infancy.
- In 1999, Duran-McKinster et al9 noted that the age at onset of neurologic signs ranged from 1 month to 11 years.
- In 2001, Ivanovich et al8 noted a 12-year-old boy with ES and compared this condition with Chédiak-Higashi syndrome and Griscelli syndrome. This boy demonstrated severe developmental delay, seizure activity, exotropia, nystagmus, ataxia, and silvery-gray hair and eyebrows. The skin of this patient was not hypopigmented; rather, it was bronzed with diffuse freckling in sun-exposed areas. The boy had no history of recurrent infections, and results from immunologic studies were normal. Ivanovich et al8 suggested that this patient is reportedly the oldest living child with ES. It is not clear if the patient had ES.
Clinical
History
Children with ES can manifest with disease as early as 1 month of life or in early childhood. The skin and neurologic systems are the most commonly affected. Psychomotor impairment may have 2 forms of presentation: congenital or infantile.
- Some patients with ES have severe mental retardation since the first months of life. They do not seem to recognize their parents, they have almost complete absence of movements, they are severely hypotonic, and they are unresponsive to external stimuli.
- Another group of patients had no history of early neurologic impairment and developed normally. By the time the patients were aged 3-11 years, they developed several rapidly regressive psychomotor processes. They were unable to speak, walk, and feed themselves, and they were bedridden.
- Other symptoms include severe migraine headaches followed by hemiparesis, leg weakness progressing to severe hypotony involving the entire body, atactic cerebellar movements progressing into an inability to maintain muscular tone of the neck, profound hypotonia, and a resultant inability to walk or to speak.
- Once the neurologic alterations occur, most patients have convulsive episodes. Neuromuscular disorders include constant severe generalized hypotonia as well as hyperactive deep tendon reflexes.
- In a study by Duran-McKinster et al in 1999,9 the age at onset of neurologic signs ranged from 1 month to 11 years.
- The manifestations of the brain pathology of ES consisted of severe muscular hypotonia, ocular alterations, and seizures.
- Duran-McKinster et al9 note mental retardation that first occurred before age 6 months in 4 patients.
- Psychomotor development was appropriate in 3 patients; however, the patients suddenly demonstrated a regressive neurologic process. Four patients died between age 6 months and 3 years after neurologic dysfunction began.
- Others have noted spastic hemiplegia or quadriplegia and seizures that decrease over time.
Physical
- Immune impairment is absent.
- Ophthalmologic findings include nystagmus, diplopia, and congenital amaurosis.
- Respiratory infections can occur, but their relationship to the disease is unclear.
- The scalp and body hair, the eyebrows, and the eyelashes have a silvery color. The skin can have a bronze or deep-tan color after sun exposure.
- Chen10 noted that omphalocele can be a finding in persons with ES.
Causes
The pathophysiology of ES is not fully understood (see Pathophysiology).
More on Elejalde Syndrome |
 Overview: Elejalde Syndrome |
| Differential Diagnoses & Workup: Elejalde Syndrome |
| Treatment & Medication: Elejalde Syndrome |
| Follow-up: Elejalde Syndrome |
| References |
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References
Elejalde BR, Valencia A, Gilbert EF. Neuro-ectodermal melanolysosomal disease: an autosomal recessive pigment mutation in man [abstr]. Am J Hum Genet. 1977;29:39A.
McKusick VA, Rasmussen SA. 256710 Neuroectodermal Melanolysosomal Disease. Online Mendelian Inheritance in Man. Available at http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?256710. Accessed March 26, 2003.
Lambert J, Vancoillie G, Naeyaert JM. Elejalde syndrome revisited. Arch Dermatol. Jan 2000;136(1):120-1. [Medline].
Sanal O, Yel L, Kucukali T, Gilbert-Barnes E, Tardieu M, Texcan I, et al. An allelic variant of Griscelli disease: presentation with severe hypotonia, mental-motor retardation, and hypopigmentation consistent with Elejalde syndrome (neuroectodermal melanolysosomal disorder). J Neurol. Jul 2000;247(7):570-2. [Medline].
Anikster Y, Huizing M, Anderson PD, Fitzpatrick DL, Klar A, Gross-Kieselstein E, et al. Evidence that Griscelli syndrome with neurological involvement is caused by mutations in RAB27A, not MYO5A. Am J Hum Genet. Aug 2002;71(2):407-14. [Medline].
Wilson SM, Yip R, Swing DA, O'Sullivan TN, Zhang Y, Novak EK, et al. A mutation in Rab27a causes the vesicle transport defects observed in ashen mice. Proc Natl Acad Sci U S A. Jul 5 2000;97(14):7933-8. [Medline].
Afifi HH, Zaki MS, El-Kamah GY, El-Darouti M. Elejalde syndrome: clinical and histopathological findings in an Egyptian male. Genet Couns. 2007;18(2):179-88. [Medline].
Ivanovich J, Mallory S, Storer T, Ciske D, Hing A. 12-year-old male with Elejalde syndrome (neuroectodermal melanolysosomal disease). Am J Med Genet. Feb 1 2001;98(4):313-6. [Medline].
Duran-McKinster C, Rodriguez-Jurado R, Ridaura C, de la Luz Orozco-Covarrubias M, Tamayo L, Ruiz-Maldonando R. Elejalde syndrome--a melanolysosomal neurocutaneous syndrome: clinical and morphological findings in 7 patients. Arch Dermatol. Feb 1999;135(2):182-6. [Medline].
Chen CP. Syndromes and disorders associated with omphalocele (III): single gene disorders, neural tube defects, diaphragmatic defects and others. Taiwan J Obstet Gynecol. Jun 2007;46(2):111-20. [Medline].
Bahadoran P, Ortonne JP, Ballotti R, de Saint-Basile G. Comment on Elejalde syndrome and relationship with Griscelli syndrome. Am J Med Genet A. Feb 1 2003;116(4):408-9. [Medline].
Cahali JB, Fernandez SA, Oliveira ZN, Machado MC, Valente NS, Sotto MN. Elejalde syndrome: report of a case and review of the literature. Pediatr Dermatol. Jul-Aug 2004;21(4):479-82. [Medline].
Duran-McKinster C, Rodrigez-Jurado R, Orozco-Covarrubias L, Tamayo-Sanchez L. Clinical and morpholigical findings in Chediak-Higashi syndrome, Griscelli syndrome and Elejalde syndrome. 20th World Congress of Dermatology. 2002;P1583.
Elejalde BR, Holguin J, Valencia A, Gilbert EF, Molina J, Marin G, et al. Mutations affecting pigmentation in man: I. Neuroectodermal melanolysosomal disease. Am J Med Genet. 1979;3(1):65-80. [Medline].
Hornyak TJ. The developmental biology of melanocytes and its application to understanding human congenital disorders of pigmentation. Adv Dermatol. 2006;22:201-18. [Medline].
Lambert J, Naeyaert JM, De Paepe A, Van Coster R, Ferster A, Song M, et al. arg-cys substitution at codon 1246 of the human myosin Va gene is not associated with Griscelli syndrome. J Invest Dermatol. Apr 2000;114(4):731-3. [Medline].
Libby RT, Lillo C, Kitamoto J, Williams DS, Steel KP. Myosin Va is required for normal photoreceptor synaptic activity. J Cell Sci. Sep 1 2004;117(Pt 19):4509-15. [Medline].
Scheinfeld NS. Syndromic albinism: a review of genetics and phenotypes. Dermatol Online J. Dec 2003;9(5):5. [Medline].
Silhánová E, Plevová P, Curík R, Kaspercík I, Krepelová A. Elejalde syndrome--a case report. Am J Med Genet A. Oct 15 2006;140(20):2223-6. [Medline].
Further Reading
Keywords
ES, neuroectodermal melanolysosomal disease, NEMLD, Griscelli syndrome, Chédiak-Higashi syndrome
