Boucher Neuhäuser syndrome ... (Boucher-Neuhäuser syndrome) - Gen PNPLA6

Syndrome Boucher-Neuhäuser, also known as spinocerebellar ataxia with hypogonadotropic hypogonadism and chorioretinal dystrophy, is a rare condition that affects movement, vision and sexual development. This syndrome is part of a spectrum of neurological processes known as PNPLA6 related disorders that share a genetic cause and having a combination of superposed characteristics.

Syndrome Boucher-Neuhäuser is characterized by three specific features: ataxia, hypogonadotropic hypogonadism and chorioretinal dystrophy. Syndrome Boucher-Neuhäuser, ataxia develops as a result of atrophy in the cerebellum. The hypogonadotropic hypogonadism, affects the production of hormones that direct sexual development. Affected individuals have a delay in development of own signs of puberty, such as growth of facial hair, voice change in boys, and the onset of menstruation and breast development in women. Other hormonal abnormalities lead to short stature in some affected individuals. The third feature of Boucher-Neuhäuser syndrome is chorioretinal dystrophy. These ocular abnormalities impair vision. In addition, affected individuals may show abnormal eye movements, including nystagmus.

The main features of Boucher-Neuhäuser syndrome may begin at any time from infancy to adulthood, although at least one characteristic usually occurs in adolescence. Often, ataxia is the first symptom of the disease, but vision problems or delayed puberty may be the first finding. Vision problems and movement progress slowly throughout life and can lead to blindness or need a wheelchair for mobility of people most severely affected. In addition, people with Boucher-Neuhäuser syndrome may have additional medical problems, including spasticity, dysarthria and cognitive impairment.

Most cases of Boucher-Neuhäuser syndrome are due to mutations in the PNPLA6 (patatin like phospholipase domain containing 6) gene. This gene, located on the short arm of chromosome 19 (19p13.2), encoding the protein of neuropathy target esterase (NTE), involved in the metabolism of certain lipids. Specifically, NTE decomposes lysophosphatidylcholine, which is one of several compounds found in the outer membranes of surrounding cells. The correct concentrations of these compounds are critical to the stability of cell membranes. NTE helps regulate the concentrations of lysophosphatidylcholine, which can be harmful to the cells in large amounts. The NTE protein is greater extent in the nervous system, which plays an important role in maintaining the stability of the membranes surrounding neurons and axons. NTE can also play a role in the release of hormones from the pituitary gland, a process requiring particular changes in the cell membrane and appears to involve the lipids found there.

There are more than a dozen mutations in the gene responsible PNPLA6 Boucher-Neuhäuser syndrome. It is believed that the identified mutations alter the function of the protein NTE. Although it is unclear how this reduction in function results in the signs and symptoms of the disease, it is believed that impaired metabolism lysophosphatidylcholine alters the balance of compounds in the cell membrane. This imbalance can damage axons, which causes problems of movement and vision that characterize the syndrome Boucher-Neuhäuser. The imbalance is also believed that damages the release of hormones involved in sexual development, which explains the delay of puberty in affected individuals.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome Boucher-Neuhäuser, by complete PCR amplification of exons PNPLA6 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).