Elejalde Syndrome

Rare inherited disorder characterized by silvery hair, pigment abnormalities of the skin, and early-onset central nervous system dysfunction.

Melanolysosomal Neurocutaneous Syndrome. (Caveat: The name Elejalde syndrome has also been used synonymously for Acrocephalopolysyndactylous Dysplasia. To avoid confusion, we recommend reserving this name for the syndrome described here.)

Approximately 11 cases have been reported.

Autosomal recessive. Candidate genes for Elejalde syndrome have been sought in a variety of genes involved in organellogenesis and intracellular trafficking. These genes are directly or indirectly involved in pigmentation disorders throughout the expression of adaptor-like protein complex(AP)-3 factor, which is involved in the budding of coated vesicles from the Golgi system.

Abnormal melanocytes, melanosomes, and inclusion bodies in fibroblasts may be present. There are speculations that myosin V protein may be affected and probably responsible for the severe generalized hypotonia. The molecular basis of the disease remains to be elucidated.

Light microscopy of the hair is characterized by the presence of small and large melanin clumps irregularly distributed along the hair shaft but predominantly in the medulla. Skin biopsy specimens may reveal a normal number of melanocytes but irregular distribution and irregular size of melanin granules in the basal layer. Electron microscopy of the skin reveals melanocytes with melanosomes of various sizes and at various developmental stages. Because of a maturation defect, melanization of the melanosomes is incomplete; however, in contrast to Griscelli and Chediak-Higashi Syndrome (the two other “Silvery Hair Syndromes”), both humoral and cellular immunity are normal.

Scalp hair, eyelashes, and eyebrows are silver. Sun exposure leads to pronounced and long-lasting skin tanning. The age at onset of neurologic signs can range from 1 month to 11 years and include severe muscular hypotonia, ataxia, seizures, hyperreflexia or hyporeflexia, spastic or flaccid hemiplegia or quadriplegia, and ocular features (e.g., congenital amaurosis, nystagmus, diplopia, pupillary areflexia). Mental retardation with delayed psychomotor development usually is obvious in the first month of life. Magnetic resonance imaging can demonstrate cerebellar hypoplasia/atrophy.

No data regarding anesthetic management or pharmacological implications in this disorder have been published. Seizure control, assessment of muscular hypotonia, and the potential presence of recurrent pulmonary aspirations are the main focus points in the preoperative evaluation. A chest radiograph might be indicated. Failure to thrive may be present secondary to poor feeding and results in electrolyte and fluid imbalances. Blood work should include serum levels of electrolytes. Depending on the type and extent of surgery, prolonged postoperative mechanical ventilation may be required. Mental retardation may limit patient cooperation. Sedative premedication and/or the presence of the primary caregiver during induction of anesthesia may be helpful.

Recurrent aspiration is a described complication in this syndrome. A rapid-sequence induction technique is recommended. Severe hypotonia may require reduced amounts or no neuromuscular blocking agents. Positioning may be difficult in the presence of spastic paraplegia or tetraplegia.

In the presence of severe hypotonia, use of depolarizing neuromuscular relaxants may result in exaggerated hyperkalemia. The sensitivity to nondepolarizing blocking agents can be increased and should be properly monitored with a peripheral nerve stimulator.

Griscelli Syndrome: Albinism with immunodeficiency characterized by partial pigmentary dilution of the skin and hair (silvery-gray hair), frequent infections, neurologic abnormalities, and fatal outcome caused by uncontrolled T-lymphocyte and macrophage activation syndrome. The clinical features include the presence of large clumps of pigment in hair shafts and an accumulation of melanosomes in melanocytes.

Chediak-Higashi Syndrome: Frequently fatal disease of childhood characterized by the association of immune deficiency, partial oculocutaneous albinism, easy bruisability, bleeding, and recurrent infections.

Hermansky-Pudlak Syndrome (HPS): Autosomal recessive disorder presenting with oculocutaneous albinism, visual impairment, platelet dysfunction, severe bleeding disorder, and progressive symptoms including pulmonary fibrosis, inflammatory bowel, and kidney disease. The severity of this syndrome ranges from very mild with few symptoms to severe and disabling.

Oculocerebral with Hypopigmentation Syndrome: Extremely rare autosomal recessive inherited syndrome (fewer than 20 cases have been described). Most symptoms are present at birth or develop shortly thereafter and may include very light skin color and silvery hair in combination with ophthalmologic (microphthalmia, corneal clouding, cataract, ectropion) and central nervous system anomalies (dolichocephaly, mental retardation, athetosis, ataxia, spastic paraplegia or tetraplegia). Gingival fibromatosis may develop at the age of emergence of the first teeth and may result in complete coverage of the teeth and become so significant that ventilation is impaired. Ventilation can be decreased further by a dysfunctional diaphragm.