Schwartz-Jampel syndrome (ORPHA:800)
A rare, genetic neuromuscular disease characterized by permanent myotonia, mask-like facies (with blepharospasm, narrow palpebral fissures, small mouth with pursed lips and puckered chin) , and chondrodysplasia (variably manifesting with short stature, pectus carinatum, kyphoscoliosis, bowing of long bones, epiphyseal, metaphyseal, and hip dysplasia).
Epidemiology
Approximately, 130 cases have been described in the literature to date.
Clinical description
Presentation is typically by 1 year to 2 years of age, but may occur earlier, with myotonia, maske-like facies, short stature, non-progressive muscle weakness, muscle hypertrophy, progressive restriction of range of motion and paucity of subcutaneous tissue. Facial features consist of blepharospasm, progressive blepharophimosis, pursed lips and a puckered chin. Micrognathia, low-set ears with folded helices and dystopia canthorum have also been reported. The myotonia is characterized by continuous muscle activity recorded on electroneuromyography. Limited joint mobility leads to an unsteady gait. Joint stiffness is progressive, reaching its peak during adolescence The severity of chondrodysplasia is variable and may consist of flattening of the vertebral bodies, hip dysplasia, metaphyseal widening, slender diaphyses, kypho-scoliosis, multiple joint contractures and bowing of long bones. Rarely, myopia, inguinal and umbilical hernias and micro-orchidism have been reported.
Etiology
Loss of function mutations in HSPG2 (1p36) are causative. HSPG2  encodes perlecan, a major component of the cellular matrix that plays an important role in maintaining cartilaginous tissue integrity and regulating muscle excitability. The exact pathogenesis is unknown.
Diagnostic methods
Diagnosis is established by demonstration of both myotonia via electromyography and chondrodysplasia via radiographs. Genetic testing may confirm diagnosis.
Differential diagnosis
Schwartz-Jampel syndrome (SJS) is non-allelic with Stuve-Wiedemann syndrome, a severe skeletal dysplasia that is typically fatal during the neonatal period and was formerly described as SJS type 2. Other differential diagnosis should include Freeman Sheldon and Marden Walker syndrome and, in cases with minimal skeletal abnormalities, myotonic disorders ( including myotonia congenita, myotonia permamens, and myotonic dystrophy).
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to affected families, informing them that the risk of disease transmission is 25% where both parents are unaffected carriers.
Management and treatment
The management of patients with SJS is primarily supportive and best offered by a team comprising a neurologist, a geneticist, a physical therapist, an orthopedic surgeon, an ophthalmologist and a psychologist. Medical treatment with muscle relaxants and antiepileptic drugs, such as carbamazepine, phenytoin, or procainamide, aimed to alleviate myotonia has limited usage, although early initiation of treatment may limit the extent of disability. Physical therapy is important to prevent contracture formation and fixed skeletal deformity. Botulinum toxin A injections for blepharospasm has been reported with limited and variable results Rarely, surgical intervention is considered for blepharospasm including orbicularis oculi myectomy or levator aponeurosis resection improve functional and cosmetic outcome. Malignant hyperthermia is a potentially lethal complication of anesthesia.
Prognosis
Progressively worsening blepharospasm is an important morbidity that can interfere with vision. The disease appears to stabilize after adolescence and does not affect life span.

                            Last update: 
                            February 2020


                            - Expert reviewer(s): 
                            Pr Bertrand FONTAINE