Schwartz-Jampel syndrome

See https://youtu.be/ZIXoYHYEnkg
https://www.youtube.com/watch?v=OOCuFlbz63E
https://www.youtube.com/watch?v=gTMq1WKcqZ4
https://www.youtube.com/watch?v=gZZESKD1dYg

Chandra SR, Issac TG, Gayathri N, Shivaram S. Schwartz-Jampel syndrome . J Pediatr Neurosci 2015;10:169-71

Abstract

Schwartz-Jampel syndrome is a very rare congenital myotonic syndrome with typical phenotypic and electrophysiological features. Diagnosis is made by awareness into the typical phenotypic characters.

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From the article

This condition also called as chondrodystrophic myotonia was first described in the year 1962 by Schwartz and Jampel as congenital blepharophimosis associated with unique generalized myopathy. [ The prevalence is <1/million and total reported cases are <100.  This is inherited as autosomal dominant and autosomal recessive. Most patients become symptomatic between 3 years and 10 years. They present with typical phenotypic features, characterized by short stature, mask-like facies, epicanthic fold, receding chin, upturned nose, long philtrum, short neck, pinched face, low-set ears, high arched palate, prominent muscles, and high pitched voice. The diagnostic findings are typical facial appearance, muscle hypertrophy, and continuous muscle fiber activity.  They have slow movements with arms semi-flexed, toe walking in addition to difficulty in opening the mouth, mild kyphosis, contractures at elbow, spine, pelvis, metaphyseal deformities, lumbar lordosis, limited movement in major joints, other complications like hydrocephalus, carpal tunnel syndrome, myelopathy, recurrent infections, stridor and mental retardation etc. But the radiological assessment of bones generally does not yield osseous or epiphyseal changes. However, normal intelligence and normal skeletal system is also known. They show myotonia clinically and electrophysiologically. In general, biochemistry, cytogenetics, and histology are not very helpful. Myopathic, neurogenic, and normal histopathological features are reported. Immunohistochemistry showing abnormal fibers with accumulation of desmin, vimentin, titin with fast, slow, fetal, and embryonic isoforms suggesting regeneration, type 1 fiber predominance and fiber type grouping suggestive of re-innervation can also be seen. Electron microscopy shows abnormalities in the form of dilated T system, Z band streaming, dilatation of mitochondria and also denervation atrophy. Interruption in sarcomere including the Z disc, focal disarray of myofibrils, increased subsarcolemmal sarcoplasm, vacuoles in between bundles of myofibrils, abnormal thin filaments, clusters of glycogen, myelinated materials are also reported. This disease has been mapped to Schwartz-Jampel syndrome locus on chromosome 1(1p34-p36.1).  Electrophysiology shows normal motor sensory conductions with characteristic electromyographic features in the form of prolonged and persistent discharges following needle insertion, repetitive discharges, high-frequency discharges, after discharges, dive-bomber sound, and normal motor units. Complex repetitive discharges consisting of potentials which are closely time locked are seen as a result of ephaptic impulse transmission between fibers.   Different patients, however, can show different patterns with a spectrum varying from typical myotonic discharges to discharges with no variation in amplitude and frequency or combination. Bizarre high-frequency patterns are also reported.   The discharges are from muscle as they cannot be suppressed by curare, but agents that block sodium channels in muscle like procainamide inhibit it like in Isaac's syndrome. The disease is caused by mutation in perlecan, a heparitin sulfate proteoglycan which is in the basement membrane of muscles and cartilage. Loss of its function causes altered clustering of acetylcholine esterase and abnormal expression of ion channels. Treatment with procainamide or mexiletene can be useful, but no benefit is seen with diphenylhydantoin, diazepam, barbiturates, etc. Early treatment with carbamazepine is reported to have helped few patients.   It is important to recognize this condition as they are prone for fatal hyperthermia following anesthesia.  Prenatal diagnosis is possible in the mid trimester ultrasound by specifically looking for constant flexion of fingers, decreased fetal activity, and shortening and bowing of femurs. Other myotonic syndromes like congenital myotonic dystrophy, dominant and recessively inherited myotonia congenita and paramyotonia congenita are phenotypically and genotypically distinct. Freeman-Sheldon syndrome is a close mimic with whistling face, puckered lips, microstomia, long philtrum, and dimpled chin. There is ulnar deviation of the hand causing windmill vane configuration. Marden-Walker syndrome is associated with immobile facies, blepharophimosis, mental retardation, congenital joint contractures, and failure to thrive.