Elejalde Syndrome

Updated: Jan 27, 2020
  • Author: Chris G Adigun, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
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Elejalde syndrome (ES) was first described in 1977 [1] in 3 consanguineous families in Columbia. Elejalde syndrome is also referred to as neuroectodermal melanolysosomal disease. [2] The largest series of patients has been reported in Mexico. It has been suggested that Elejalde syndrome is the same disease entity as Griscelli syndrome type 1 caused by MYO5A gene mutations. [3] Still, the exact basis for Elejalde syndrome remains to be defined. [4]  Elejalde syndrome continues to be discussed by clinicians who assess children with silver hair. [5, 6]

Silvery hair and CNS dysfunction characterize this rare autosomal recessive syndrome. The main cutaneous features of Elejalde syndrome 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. Elejalde syndrome 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. Elejalde syndrome must be distinguished from Chédiak-Higashi syndrome [7, 8]  (CHS) and Griscelli syndrome (GS).

Elejalde syndrome (Online Mendelian Inheritance in Man [OMIM] entry #256710 [3] ) should not be confused with another Elejalde syndrome (OMIM entry 200995), also known as acrocephalopolydactylous dysplasia. A number sign (#) denotes the entry for Elejalde syndrome because neuroectodermal melanolysosomal disease, or Elejalde disease, and Griscelli syndrome type 1 (GS1; 214450) are really the same entity. GS1 is caused by mutation in the MYO5A gene (160777). [9]

Modern genetic studies have more firmly fixed the relative place of Elejalde in children and adults. [10, 11]

While the syndrome is rare, Elejalde syndrome remains in the differential diagnosis of CHS and GS and is actively discussed in several papers when assessing the combination of silver hair and immunodeficiency. [12, 13]

Saini et al equated GS1 with Elejalde syndrome. [14] They noted the case of a 3-year-old boy with a viral infection who experienced fever, regression of neurological function, focal seizures, and altered sensorium. Physical findings included spastic quadriparesis. extensor plantars, silvery-gray hair, bilateral papilledema, hepatosplenomegaly, and brisk muscle-stretch reflexes. The child was noted to have normal retinae, irises, and skin pigmentation. GS1 (also known as Elejalde syndrome) was confirmed using hair microscopy.



The pathophysiology of Elejalde syndrome 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. Molecular defects that underlie a variety of pigmentary disorders have been defined and provide a framework for the understanding of syndromes such as Elejalde syndrome. [15]

In 2000, Lambert et al [16] stated that the neurologic abnormalities seen in Elejalde syndrome 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 Elejalde syndrome must be sought in the variety of genes involved in organellogenesis and intracellular trafficking.

In 2000, Sanal et al [17] referred to neuroectodermal melanolysosomal disease as an allelic variant of Griscelli syndrome. In 2002, Anikster et al [18] suggested that families previously thought to have Griscelli syndrome due to mutations in the MYO5A gene (OMIM entry #160777) may in fact have had Elejalde syndrome.

The absence of immunologic defects distinguishes Elejalde syndrome from Griscelli syndrome. Sanal et al [17] suggest that ashen is a mouse model of Elejalde syndrome; however, in 2000, Wilson et al [19] 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). [3]

Myosin-Va is a very important gene in the brain. [20]  Its gene product is involved in the transport mechanism of the endoplasmic reticulum with the Purkinje neuron dendritic spines. [21] It is involved with cerebellar learning function and neural plasticity. [22]




United States

Elejalde syndrome is extremely rare, with 20 patients reported as of 2019. [13]


In 1977, Elejalde et al [1] described a new pigment mutation in two males and one female, each from a consanguineous marriage in an inbred Colombian kindred. Whether the disease is more common in Columbia is unknown. A large series of patients with Elejalde syndrome is from Mexico, but whether this finding indicates an increased incidence is unknown. [23]

Afifi et al [24] reported on an Egyptian male patient with Elejalde syndrome who had silvery hair since birth, generalized hypopigmentation, severe primary CNS dysfunction, and normal hematological and immunologic profiles.

A 2011 survey of hypopigmentary diseases in India noted no cases of Elejalde syndrome. [25]


A racial predilection is not known.


Elejalde syndrome is an autosomal recessive disease; therefore, no difference in sexual frequency exists.


Elejalde syndrome usually starts to manifest during infancy. In 1999, Duran-McKinster et al [23] noted that the age at onset of neurologic signs ranged from 1 month to 11 years.

In 2001, Ivanovich et al [26] noted a 12-year-old boy with Elejalde syndrome 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 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 al [26] suggested that this patient is reportedly the oldest living child with Elejalde syndrome. It is not clear if the patient had Elejalde syndrome.



All cases of Elejalde syndrome but one have been reported as being fatal; therefore, the prognosis is suboptimal. Patients with Elejalde syndrome undergo neurologic collapse and eventually are not able to move or care for themselves.

Death occurs from neurologic collapse in childhood. One report noted deaths of children aged 3 months to 4 years. Another report [26] noted that a patient with Elejalde syndrome was alive at age 12 years. Another report noted that one patient with Elejalde syndrome died of respiratory infection at age 5.5 years.

The main morbidity comes from neurologic dysfunction and psychomotor regression and dysfunction.