LAS VEGAS — Genetic disorders associated with silvery hair are almost uniformly fatal in children, most often as a result of accompanying immunologic or neurologic abnormalities.
Natural light reveals hair the color of lead and with a “peculiar” shine in children with Chédiak-Higashi syndrome, Griscelli syndrome, and Elejalde syndrome, and in the rare child whose unusual pigmentation is not associated with systemic defects, Dr. Carola Durán-McKinster said at a dermatology seminar sponsored by Skin Disease Education Foundation.
A natural history study of children with these syndromes at the National Institute of Pediatrics of Mexico, where Dr. Durán-McKinster is head of pediatric dermatology, found the diseases were fatal in 8 of 10 children with Chédiak-Higashi syndrome, all 7 children with Gris-celli syndrome, and 8 of 10 with traditional Elejalde syndrome. Four children who did not fit diagnostic criteria for any systemic syndrome survived.
Children with silvery hair syndromes have skin that is so hypo-pigmented at birth they may resemble children with albinism, though after exposure to sunlight, their skin becomes deeply, bronzed, said Dr. Durán-McKinster, who is on the dermatology faculty at Universidad Nacional Autónoma de México. Careful examination of an infants' hair is critical to making a diagnosis, often with important prognostic and treatment implications.
A decrease or total loss of hair or skin color can arise from a mutation in any of 127 genes involved in the complex pigmentation process, which involves distribution of melanin polymers produced in the melano-cytes and transferred to neighboring keratinocytes. Gene mutations that express two critical proteins involved in this process, myosin 5A and Rab27, are key to abnormalities in two silvery hair syndromes, Elejalde and Griscelli, respectively.
Dermatologists may readily recognize the light hair characteristic of albinism or poliosis (often, a white forelock) that may be an isolated genetic feature or may be associated with deafness, as in Waardenburg's syndrome.
Unusual silvery-gray hair is less common and should be investigated with light microscopy and a biopsy. Histopathologic findings include a clustering of melanin in basal melanocytes, with nearly absent pigment in adjacent keratinocytes—features especially well visualized with Fontana-Masson stain.
Light microscopy of the hair shaft can show a pattern of melanin distribution virtually pathognomonic for Chédiak-Higashi syndrome, in which small clumps of melanin are evenly distributed in contrast to the irregular spread of giant and small melanin clumps in Elejalde.
A prompt and accurate diagnosis can lead to appropriate immunologic or neurologic testing and management, which may include antibiotics and antivirals, intravenous immunoglobulin, blood transfusions, and bone marrow transplantation.
Dr. Durán-McKinster disclosed having no relevant conflicts of interest. SDEF and this news organization are wholly owned subsidiaries of Elsevier.
Root Cause May Involve One of Four Diagnoses
Dr. Durán-McKinster described the following silvery hair syndromes:
▸ Chédiak-Higasi. In this rare, autosomal recessive disorder, giant inclusion bodies are found in granule-containing cells. Children are immunocompromised. Lymphocytes and histiocytes accumulate in the liver, spleen, lymph nodes, and bone marrow, causing hepatosplenomegaly, bone marrow infiltration, bleeding, and hemophagocytosis. High doses of methylprednisolone and splenectomy may help; allogeneic bone marrow transplantation is done when possible.
▸ Griscelli syndrome. Children with this severe, autosomal recessive immunodeficiency syndrome can develop hemophagocytic syndrome, with infectious episodes, and pancytopenia, hypertriglyceridemia, hypofibrinogenemia, and hypoproteinemia. Treatment of choice is allogeneic bone marrow transplantation.
▸ Elejalde syndrome. This is also an autosomal recessive disease with severe neurologic abnormalities, including hypotonia, mental retardation, and progressive psychomotor impairment until death. Ocular abnormalities and abnormal melanocytes and melanosomescan also occur.
▸ Silvery hair without associated abnormalities. Children with a syndrome resulting from a mutation of the gene that encodes for melanophilin have silvery hair and bronzed skin after sun exposure, but do not exhibit immunologic or neurologic complications.