Stüve-Wiedemann syndrome ... (Stüve-Wiedemann syndrome) - Gen LIFR
The Stuve-Wiedemann is a serious condition characterized by bone abnormalities and autonomic nervous system dysfunction. The condition is evident at birth, and its key features include tilt of the long bones of the legs, difficulty in feeding and swallowing, and severe episodes of hyperthermia. Besides bowlegged, affected children may have arched arms, camptodactilia, joint deformities elbows and knees that limit their movement, abnormalities of the pelvic bones and osteopenia. In addition, affected children may also sweat excessively, even when no body temperature rises, or have a reduced ability to feel pain. Many infants do not survive beyond childhood due to problems to regulate breathing and body temperature; However, some people with this syndrome live into adolescence or later.
Problems with breathing and swallowing usually improve in affected children survive infancy; However, they still have difficulty regulating body temperature. Over time, the inclination of the leg bones worsens, so that those affected can develop prominent joints, scoliosis and spontaneous bone fractures. Other manifestations can include absence of fungiform papillae and loss of certain reflections, as the corneal reflex and patellar reflex. A process formerly known as Schwartz-Jampel syndrome type 2 is now considered as part of the Stüve-Wiedemann syndrome.
The Stuve-Wiedemann is usually due to mutations in the LIFR gene, located on the short arm of chromosome 5 (5p13-p12) encoding the receptor of leukemia inhibitory factor (LIFR). This receptor spans the cell membrane, allowing it to bind ligands outside the cell and transmitting signals into the cell that help the cell to respond to its environment. LIFR acts as a receptor for a molecule known as leukemia inhibitory factor (LIF) and other ligands. LIFR signaling can control several cellular processes including growth, proliferation, differentiation and cell survival. This signaling is important for inhibition of leukemia as well as bone formation and development of nerve cells. Also it appears to play an important role in development and normal functioning of the autonomic nervous system that controls involuntary body processes, such as the regulation of respiratory rate and body temperature.
They have identified at least 27 mutations in the LIFR gene in people with Stüve-Wiedemann syndrome. Most of these mutations inhibit protein synthesis of any LIFR. Other mutations result encoding a nonfunctional altered protein. Without functional LIFR, signaling deteriorates, which disrupts normal bone growth causing osteopenia, bowlegged and other common bone problems in Stüve-Wiedemann syndrome. Furthermore, the development of nerve cells is altered, particularly those involved in the autonomic nervous system, leading to problems with breathing, feeding and regulating body temperature. In a small number of people with Stüve-Wiedemann syndrome they have not been identified mutations in the LIFR gene. It is likely that other unidentified genes may be involved in the development of this process.
The Stuve-Wiedemann is inherited as an autosomal recessive pattern, which means that both copies of the gene in every cell have mutations. The parents of an individual with an autosomal recessive disorder each 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 Stuve-Wiedemann, by complete PCR amplification of the exons of the LIFR 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).