Elejalde syndrome

Overview

Elejalde syndrome, also known as neuroectodermal melanolysosomal disease, is an extremely rare autosomal recessive genetic disorder characterized by a combination of severe neurological impairment and pigmentary abnormalities of the skin and hair. It belongs to a group of disorders called silvery hair syndromes, which also include Chediak–Higashi and Griscelli syndromes. Elejalde syndrome is distinguished by neurological deterioration and silvery, metallic hair, without the immunodeficiency seen in related syndromes.

Causes

Elejalde syndrome is caused by mutations in the MYO5A gene, which encodes the myosin-Va protein. This protein is essential for intracellular transport, especially in pigment cells (melanocytes) and neurons. Mutations disrupt the movement of melanosomes (pigment-containing organelles) and vesicles within cells, leading to abnormal pigmentation and severe neurological dysfunction. The condition follows an autosomal recessive inheritance pattern, meaning both parents must carry one copy of the defective gene for their child to be affected.

Symptoms

Symptoms of Elejalde syndrome typically appear in early infancy and involve both the skin and nervous system. Major features include:

• Silvery or metallic hair: Especially on the scalp, eyelashes, and eyebrows, due to abnormal melanin distribution

• Hypopigmented skin: Pale or patchy skin with abnormal pigmentation

• Severe neurological deficits:

  • Hypotonia (reduced muscle tone)

  • Seizures

  • Developmental delay

  • Progressive motor and cognitive decline

  • Spasticity and paralysis in later stages

• Visual impairment: May be present due to neurological involvement

Unlike Chediak–Higashi syndrome, Elejalde syndrome typically does not involve immunodeficiency or increased susceptibility to infections.

Diagnosis

Diagnosis is based on clinical features, microscopic examination of hair, and genetic testing. Diagnostic steps may include:

• Hair shaft microscopy: Reveals large, irregular melanin clumps typical of silvery hair syndromes

• Skin biopsy: Shows abnormal melanosome distribution

• Neurological evaluation: Imaging and clinical assessments to detect brain abnormalities

• Genetic testing: Confirms mutations in the MYO5A gene

• Exclusion of other syndromes: Such as Griscelli type 1 or 2, and Chediak–Higashi syndrome, through immune function tests and gene analysis

Treatment

There is no cure for Elejalde syndrome. Treatment is supportive and focuses on symptom management and improving quality of life. Management strategies may include:

• Anticonvulsants: To control seizures

• Physical and occupational therapy: For motor support and to delay physical deterioration

• Feeding assistance: For children with poor oral-motor function or swallowing difficulties

• Regular monitoring: Neurologic, dermatologic, and ophthalmologic evaluations

• Genetic counseling: For affected families to understand inheritance and reproductive risks

Prognosis

The prognosis for Elejalde syndrome is generally poor. Most children experience profound developmental delays and progressive neurological decline. Life expectancy is significantly reduced, often due to complications related to seizures or neurological deterioration. However, because of its rarity, detailed long-term outcome data is limited. Early supportive care and intervention may help improve comfort and extend life expectancy in some cases.