Schwartz Jampel syndrome

Alternate names

Aberfeld syndrome; Burton skeletal dysplasia; Burton syndrome; Catel-Hempel syndrome; Dysostosis enchondralis metaepiphysaria, Catel-Hempel type; Osteochondromuscular dystrophy; Schwartz-Jampel syndrome; Schwartz-Jampel-Aberfeld syndrome; SJS; SJS1; Schwartz Jampel Aberfeld syndrome; Myotonic myopathy dwarfism chondrodystrophy and ocular and facial abnormalities; SJA syndrome; Chondrodystrophic myotonia; Myotonic chondrodystrophy; Myotonic myopathy, dwarfism, chondrodystrophy, ocular and facial anomalies

Definition

Schwartz-Jampel syndrome is a rare condition characterized by permanent muscle stiffness (myotonia) and bone abnormalities known as chondrodysplasia.

Epidemiology

Schwartz-Jampel syndrome appears to be a rare condition. About 150 cases have been reported in the medical literature.

Types

• Researchers originally described two types of Schwartz-Jampel syndrome.
• Type 1 has the signs and symptoms described above, while type 2 has more severe bone abnormalities and other health problems and is usually life-threatening in early infancy.
• Researchers have since discovered that the condition they thought was Schwartz-Jampel syndrome type 2 is actually part of another disorder, Stüve-Wiedemann syndrome, which is caused by mutations in a different gene.
• They have recommended that the designation Schwartz-Jampel syndrome type 2 no longer be used.
• SJS is subdivided into types 1A and 1B, differentiated by severity and age of onset.
• Type 1A, considered classic SJS, is the most commonly recognized type.
• People with type 1A typically develop more mild symptoms later in childhood, while individuals with type 1B have symptoms that are more severe and are apparent immediately after birth.

Cause

• Schwartz-Jampel syndrome is caused by mutations in the HSPG2 gene.
• This gene provides instructions for making a protein known as perlecan.
• This protein is found in the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells.
• Specifically, it is found in part of the extracellular matrix called the basement membrane, which is a thin, sheet-like structure that separates and supports cells in many tissues.
• Perlecan is also found in cartilage, a tough, flexible tissue that makes up much of the skeleton during early development.
• Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears.
• Perlecan has multiple functions, including cell signaling and the normal maintenance of basement membranes and cartilage.
• The protein also plays a critical role at the neuromuscular junction, which is the area between the ends of nerve cells and muscle cells where signals are relayed to trigger muscle contraction.

Gene mutations

• The mutations that cause Schwartz-Jampel syndrome reduce the amount of perlecan that is produced or lead to a version of perlecan that is only partially functional.
• A reduction in the amount or function of this protein disrupts the normal development of cartilage and bone tissue, which underlies chondrodysplasia in affected individuals.
• A reduced amount of functional perlecan at the neuromuscular junction likely alters the balance of other molecules that signal when muscles should contract and when they should relax.
• As a result, muscle contraction is triggered continuously, leading to myotonia.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition 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.

Onset

The signs and symptoms of this condition become apparent sometime after birth, usually in early childhood.

Signs and symptoms

The main signs and symptoms of SJS include the following:

• Short stature and other bone abnormalities, such as a short neck, outward-bowed chest (pectus carinatum), curved spine (kyphosis), a hip deformity (coxa valga), and fragile bones (osteoporosis)
• Joint contractures
• Muscle abnormalities, such as an inability to relax muscles (myotonia), increased muscle size (hypertrophy), and muscle weakness
• Characteristic facial features, including a “fixed” expression; a small, puckered mouth; a small lower jaw (micrognathia); and eye abnormalities, such as narrow eye openings (blepharophimosis), involuntary blinking or eyelid spasms (blepharospasm), and skin that covers the inner corner of the eyes (epicanthal folds)
• Less common symptoms include: a high pitched voice, bilateral carpel tunnel syndrome, and malignant hyperthermia.
• One study suggested that as many as 20% of individuals with SJS have an intellectual disability; however, most individuals with SJS have normal intelligence.

Diagnosis

• SJS is diagnosed on the basis of characteristic facial features, skeletal features, and muscle stiffness (myotonia).
• Studies that may be useful in diagnosing SJS include: blood tests (which may show elevated serum creatine kinase or adolase); imaging studies (X-ray); muscle biopsy; and electromyography (EMG)/nerve conduction studies.
• Genetic testing of the HSPG2 gene may confirm the diagnosis.

Treatment

• Treatment of SJS aims to reduce muscle stiffness and cramping and may include massage, muscle warming, and gradual strengthening exercises. Medications might also be used and may include muscle relaxants and anti-seizure medications, particularly carbamazepine.
• Botox might additionally be used to relieve eye symptoms such as blepharospasm.
• If Botox is not successful in managing eye symptoms, a variety of surgical techniques have been found to be effective.
• When considering surgery as an option, an important consideration is malignant hyperthermia, an associated complication, that can increase the risk of adverse outcomes.

Prognosis

• Most individuals with SJS have a good long-term outlook (prognosis) with a nearly normal life expectancy.
• Symptoms may remain stable, or worsen over time, causing increased discomfort.
• There is an increased risk of malignant hyperthermia, which may lead to adverse outcomes if not identified prior to surgical intervention or managed correctly during surgery.

NIH genetic and rare disease info

• NIH info on Schwartz Jampel syndrome

Schwartz Jampel syndrome is a rare disease.

Schwartz Jampel syndrome Resources
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