Schwartz-Jampel syndrome ... (Schwartz-Jampel syndrome) - Gen HSPG2            

The Schwartz-Jampel syndrome is a rare entity characterized by myotonia and condrodisplasia. Signs and symptoms of this disease usually manifest in early childhood. Abnormalities of the muscles and bones become worse in childhood, although most affected individuals have a normal life expectancy.

The specific characteristics of Schwartz-Jampel syndrome vary widely. Myotonia involves continuous contraction of skeletal muscles. This sustained muscle contraction causes stiffness affecting aspects such as food, sitting, walking and other movements. The sustained contraction of facial muscles causes a fixed facial expression "mask - like" with blepharophimosis and pursed lips. This facial appearance is very specific Schwartz-Jampel syndrome. Affected individuals may also manifest blepharospasm. Chondrodysplasia, it affects skeletal development, especially of the long bones of the arms and legs and hip bones. These bones are shortened and expanded at the ends, so affected individuals have short stature. Furthermore, the long bones may be abnormally curved. Other bone abnormalities associated with Syndrome Schwartz-Jampel of chest including a keel, an abnormal curvature of the spine, platyspondyly, and contractures that restrict movement.

Initially, two types of Schwartz-Jampel syndrome were described. Type 1, which is associated with signs and symptoms described above and type 2, in which affected individuals have severe bone abnormalities and other health problems and is usually fatal in early childhood. Subsequently, it was concluded that Schwartz-Jampel syndrome type 2 is actually part of another syndrome known as Stüve-Wiedemann syndrome, which is due to mutations in a different gene. Because of this, the name of Schwartz-Jampel syndrome type 2 is no longer used.

Syndrome Schwartz-Jampel of is due to mutations in the gene HSPG2 (heparan sulfate proteoglycan 2), located on the short arm of chromosome 1 (1p36.1-p34). This gene encodes the protein perlecan, which is part of the basement membrane extracellular matrix and cartilage. Perlecan is a heparan sulfate proteoglycan, a type of protein that interacts with many other proteins and has a variety of functions. In particular, perlecan is involved in signaling and cell adhesion, fangiogénesis and maintenance of basement membranes and cartilage throughout life. Protein also plays a critical role in the neuromuscular junction where the signals that trigger muscle contraction are transmitted.

They described more than 30 mutations in the gene HSPG2 in people with Schwartz-Jampel syndrome of. Most mutations reduce the amount of perlecan being encoded. Other mutations result in a version of partially functional perlecan. A reduction in the amount or function of this protein disrupts normal development of cartilage and bone, which underlies chondrodysplasia in affected individuals. It is likely that a reduced functional perlecan at the neuromuscular junction alter the balance amount of other molecules that signal muscle contraction and relaxation. As a result, muscle contraction is continuously active, leading to myotonia.

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 Schwartz-Jampel of, by complete PCR amplification of exons HSPG2 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).