Buschke Ollendorff syndrome

Buschke Ollendorff syndrome (BOS) is an association of connective tissue nevi and osteopoikilosis (small, round areas of increased bone density). The nevi are typically present on the trunk, in the sacrolumbar region (lower back and sacrum), and on the extremities (arms and legs). Occasionally, they may be on the head. The nevi are usually nontender and firm,^[1] and are typically first noticeable as slightly elevated and flattened yellowish bumps, grouped together and forming plaques that may be several centimeters in diameter. The plaques are typically of irregular shape. They are usually numerous, painless, and develop over several years.^[5] The osteopoikilosis typically occurs in the long bones, wrist, foot, ankle, pelvis, and scapula. They are harmless and usually found by chance when radiographs are taken for other purposes, although pain and limited joint mobility have been reported in some individuals.^[2] In some individuals, only skin or bone manifestations may be present.^[5]

Other signs and symptoms of BOS may include nasolacrimal duct obstruction, amblyopia ("lazy eye"), strabismus, benign lymphoid hyperplasia, hypopigmentation (abnormally light skin), and short stature. Congenital spinal stenosis (narrowing of the spine), disc herniation, clubfoot deformity, and nerve root compression may be present. Otosclerosis (abnormal growth of bone in the middle ear) with or without hearing loss may occur, but is rare.^[5]

Buschke Ollendorff syndrome (BOS) is caused by mutations in the LEMD3 gene and is inherited in an autosomal dominant manner.^[1] This means that only one changed (mutated) copy of the gene in each cell is sufficient for a person to be affected by the condition. An affected individual may have inherited a mutated copy of the LEMD3 gene from an affected parent, or they may have been born with a new (de novo) mutation. There is a 50% (1 in 2) chance for each child of an affected individual to inherit the mutated gene, and a 50% chance for each child  to not inherit the mutated gene.

It has been proposed that the inheritance of BOS shows incomplete penetrance.^[5] Penetrance refers to the proportion of people with a particular genetic change (such as a mutation in a specific gene) who exhibit signs and symptoms of a genetic disorder. If some people with the mutation do not develop features of the disorder, the condition is said to have reduced (or incomplete) penetrance. Reduced penetrance probably results from a combination of genetic, environmental, and lifestyle factors, many of which are unknown. This phenomenon can make it challenging for genetics professionals to interpret a person’s family medical history and predict the risk of passing a genetic condition to future generations.^[6] This means that not all individuals who have a new or inherited mutation in the LEMD3 gene will necessarily develop signs and symptoms of BOS.

GeneTests lists the names of laboratories that are performing genetic testing for Buschke Ollendorff syndrome. To search for laboratories conducting testing, click here.

Please note: Most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional.

There is currently no cure for BOS. Surgical removal of lesions on or under the skin may be done for cosmetic purposes. In some patients, surgical treatment of deafness may be possible. Surgery might also be necessary for some of the signs or symptoms associated with BOS. Osteopoikilosis is typically asymptomatic, but about 15-20% of individuals experience pain and joint effusions (fluid build-up). Usually, no special restrictions in activity are required for individuals with BOS.^[5]