NORD gratefully acknowledges Rebecca Hammond and Katherine McGuire, NORD Editorial Interns from the University of Notre Dame, and Mariateresa Falco, MD, Specialist in Medical Genetics, Pediatric Unit, San Giovanni di Dio e Ruggi d'Aragona University Hospital, Salerno, Italy, for assistance in the preparation of this report.
Bjornstad syndrome (BS) is an extremely rare autosomal recessive genetic disorder characterized by abnormally flattened, twisted hair shafts (pili torti) and, in most patients, deafness (congenital sensorineural hearing loss). Hearing loss at birth is variable in severity, but typically affects both ears (bilateral). Individuals with this disorder usually have dry, fragile, lusterless and/or coarse scalp hair as well as areas of patchy hair loss (alopecia).
Professor Roar Bjornstad first identified this syndrome in 1965 when he noted pili torti in eight patients and five of them also had sensorineural deafness. Since then, several other cases have been described, defining the clinical features of the syndrome.
Bjornstad syndrome is characterized by the presence of abnormally flat and twisted hair shafts defined as pili torti. BS patients usually present with dry, fragile, lusterless, and/or coarse scalp hair. When studied under an electron microscope, hair shafts from the scalp appear flattened and/or twisted (torti) at regular intervals. Body hair may exhibit the same characteristic twisting (pili torti) as scalp hair. In some patients, patchy areas of hair loss (alopecia) may be present on the scalp as well as on other areas of the body. However, the eyebrows and eyelashes are typically not affected. Light colored eyes and hair could be associated with BS and some individuals may also experience a lack of sweating (anhidrosis). Most BS patients have deafness due to an impaired ability of the auditory nerves to transmit sensory input to the brain (sensorineural hearing loss).
Hair loss typically begins during the first two years of life and, although severity of symptoms and age of onset are variable, the hair abnormality may become milder with age. Hearing loss typically develops by 3 or 4 years of age and hearing impairment may lead to speech difficulties. Intellectual disability is not a typical feature of the syndrome but has been reported occasionally.
Hypogonadism, characterized by underdevelopment of the ovaries in females and of testes in males, has been described in some BS patients, but this is not typical.
Bjornstad syndrome is caused by changes (mutations) in the BCS1L gene. This gene codes for a chaperone protein that is a member of the AAA family of ATPases. An ATPase is an enzyme that uses ATP (adenosine triphosphate), the main energy source in cells, to drive chemical reactions. This particular ATPase is involved in the assembly of complex III in the mitochondrial electron transport chain. The electron transport chain is responsible for generating the energy that cells require. Complex III also produces reactive oxygen species. When present in high numbers, these reactive compounds will cause damage to tissue. Even though this abnormal protein leads to a decrease in the activity of complex III, the complex will produce more reactive oxygen species.
The hair follicles and cells of the inner ear are particularly sensitive to these reactive oxygen species. This is thought to be the reason why hair changes and hearing loss are part of this syndrome.
Bjornstad syndrome is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% for each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
Bjornstad syndrome is an extremely rare disorder. In theory, it affects males and females in equal numbers. However, in observed cases, more females than males have been identified. Less than 50 cases are reported in the medical literature.
The diagnosis of BS may be suspected in individuals that have twisted hair, which may be obvious at birth or in the first months of life. The diagnosis is confirmed by examination of hair shafts from affected individuals under an electron microscope, demonstrating characteristic twisting of the hair shafts at regular intervals. Since the presence of this hair abnormality is suggestive of BS, all infants with this finding should be evaluated for possible sensorineural deafness that may be confirmed through a variety of specialized hearing (auditory) tests. Diagnosis is confirmed by molecular genetic testing for mutations in the BCS1L gene.
There is no specific therapy for BS patients. Treatment is symptomatic and supportive and directed toward the specific symptoms present in each child. Care may require the skills of a team of specialists. Pediatricians, specialists who assess and treat hearing loss (audiologists) and physicians who specialize in diagnosing and treating disorders involving the skin (dermatologists) may coordinate their efforts to ensure the comprehensive, systematic treatment of affected children.
The treatment of patchy hair loss (alopecia) may include the use of wigs and/or other hair replacement therapies. Early detection and treatment of sensorineural deafness is essential to help avoid possible speech problems and assisted hearing devices may be prescribed to treat hearing loss.
Early intervention is important in ensuring that children with BS reach their full potential. Services that may be beneficial may include special remedial education, special services for children with congenital sensorineural deafness, and other medical, social, and/or vocational services.
Genetic counseling is recommended for affected individuals and their families.
A recent paper describe a single case in which a ketogenic diet was initiated in a BS child and lasted six months, with partial improvement in hair growth but no improvement in hearing. Further and careful studies are needed to investigate the usefulness of this approach.
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