Bjornstad syndrome (BS) is an extremely rare autosomal recessive genetic disorder characterized by abnormally flattened, mental retardation, hearing loss, 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). Björnstad syndrome is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
The hair is brittle and breaks easily, leading to short hair that grows slowly. In Björnstad syndrome, pili torti usually affects only the hair on the head; eyebrows, eyelashes, and hair on other parts of the body are normal. The proportion of hairs affected and the severity of brittleness and breakage can vary. This hair abnormality commonly begins before the age of 2. It may become milder with age, particularly after puberty. People with Björnstad syndrome also have hearing problems that become evident in early childhood. The hearing loss, which is caused by changes in the inner ear (sensorineural deafness), can range from mild to severe. Mildly affected individuals may be unable to hear sounds at certain frequencies, while severely affected individuals may not be able to hear at all.
Symptoms
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 the severity of symptoms and age of onset is 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 testes in males, has been described in some BS patients, but this is not typical.
Causes
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 tissue damage. Even though this abnormal protein leads to a decrease in the activity of complex III, the complex will produce more reactive oxygen species.
Björnstad syndrome is caused by mutations in the BCS1L gene. The protein produced from this gene is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. In mitochondria, the BCS1L protein plays a role in oxidative phosphorylation, which is a multistep process through which cells derive much of their energy. The BCS1L protein is critical for the formation of a group of proteins known as complex III, which is one of several protein complexes involved in this process. As a byproduct of its action in oxidative phosphorylation, complex III produces reactive oxygen species, which are harmful molecules that can damage DNA and tissues.
BCS1L gene mutations involved in Björnstad syndrome alter the BCS1L protein and impair its ability to aid in complex III formation. The resulting decrease in complex III activity reduces oxidative phosphorylation. For unknown reasons, overall production of reactive oxygen species is increased, although production by complex III is reduced. Researchers believe that tissues in the inner ears and hair follicles are particularly sensitive to reactive oxygen species and are damaged by the abnormal amount of these molecules, leading to the characteristic features of Björnstad syndrome.
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 of 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.
Diagnosis
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.
Björnstad syndrome is diagnosed by observation of twisted hair, known as pili torti, which can be observed as early as birth. To confirm the presence of pili torti, the hair shafts of an individual are examined under an electron microscope. Any infants with confirmed pili torti should undergo a series of auditory tests to evaluate potential sensorineural deafness. Finally, a diagnosis of Björnstad syndrome can be confirmed by genetic testing for mutations in the BCS1L gene.[rx]
Treatment
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 are 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.
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