Schwartz-Jampel syndrome (SJS) is a term now applied to 2 different inherited, autosomal recessive conditions, sometimes termed SJS type I and SJS type II. Both are very rare. SJS type I has 2 recognized subtypes, IA and IB, which are similar, except that type IB manifests earlier and with greater severity. (See Etiology.)
The first described cases of SJS were reported in 1962 by Oscar Schwartz and Robert S. Jampel in the Archives of Ophthalmology in an article titled "Congenital blepharophimosis associated with a unique generalized myopathy."  In this paper, the authors presented the case of 2 siblings, a boy aged 6 years and a girl aged 3.5 years, who had the following clinical characteristics (see Presentation):
Congenital blepharophimosis - Ie, decreased palpebral fissure with normal eyelid development
Unusual facies characterized by a puckered facial appearance
Small muscle mass and joint deformities - Eg, coxa valga, irregularity of the capital femoral epiphyses, pectus carinatum ("pigeon breast")
Hypertrichosis of the eyelids
Slightly elevated serum aldolase level
Electromyography (EMG) was not performed. The authors proposed that the disease might represent a generalized problem with muscle and tendon development during infancy.
SJS type I
The clinical features of muscle stiffness in SJS type I somewhat resemble those seen in myotonic disorders, stiff person syndrome, and Isaacs syndrome. The stiffness does not disappear with sleep or benzodiazepine treatment (as in stiff person syndrome), and it is not abolished reliably with curare (as in Isaacs syndrome). (See Presentation.)
Neurophysiologic examination typically shows continuous electrical activity (similar to myotonic discharges). However, the electrical activity often lacks the waxing and waning quality of true electrical myotonia and might be better described as complex, repetitive discharges. At other times, the pattern resembles neuromyotonia (ie, extremely rapid, repetitive discharges that wane from an initially high amplitude). In other cases, a combination of these and other electrical patterns are seen. Perhaps a unique Schwartz-Jampel pattern exists that has not yet been fully defined. (See Workup.)
In affected patients with type I, problems with motor development frequently become evident during the first year of life. Usually, the characteristic dysmorphic features lead to an early diagnosis, no later than age 3 years. SJS types IA and IB derive from mutations of the same gene, the HSPG2 gene, which codes for perlecan, a heparin sulfate proteoglycan.
The most commonly recognized and described form of SJS is type IA, which exhibits muscle stiffness, mild (and largely nonprogressive) muscle weakness, and a number of minor morphologic abnormalities. Type IA is the classic type described by Schwartz and Jampel. It becomes apparent later in childhood and is less severe than type IB. (See Presentation.)
Type IB is apparent immediately at birth and is clinically more severe, although it is typically compatible with life and even long-term survival.
SJS type II
SJS type II, like type IB, is apparent immediately at birth. The patients look similar to those with type IB. However, it has been known for many years that type II does not map to the same chromosome as types IA and IB. It is now known that type II relates to a mutation in a different gene, the gene for the leukemia inhibitory factor receptor (LIFR). This is the same disease as Stuve-Wiedemann syndrome, which has been known separately, mainly in the rheumatologic and orthopedic literature, rather than the neurologic literature. (See Etiology.)
The cardinal features of type II are joint contractures, bone dysplasia, and small stature. Infants with type II have severe respiratory difficulties and feeding problems. Hypotonia (rather than stiffness) is prominent. Frequent bouts of hyperthermia have been described (possibly related to mitochondrial dysfunction). (See Presentation.) 
A high infant mortality rate is associated with this condition. Long-term survivors are rare but do exist, including 2 survivors, ages 3 and 12 years, reported on by Di Rocco et al in 2003.  In addition to problems with bone dysplasia, these 2 children manifested dysautonomic and neuropathic features, including reduced patellar reflexes, lack of corneal reflexes, and paradoxical perspiration at low temperatures. Their tongues lacked fungiform papillae (in addition to showing ulcerations). Reither et al reported on a survivor aged 16 years with SJS type II. (See Prognosis.) 
Considerable justification can be made for dropping the term SJS type II and simply referring to the condition as Stuve-Wiedemann syndrome. The disease is not technically that which Schwartz and Jampel described. Nevertheless, the term SJS type II is included in this discussion. Because so few patients with Stuve-Wiedemann syndrome have survived long term, most of the clinical information provided in this article pertains to SJS types IA and IB. Information pertinent to Stuve-Wiedemann syndrome will be identified as such.
Because patients with SJS have a characteristic physical appearance, they may need extra psychosocial support.
As in all diseases causing muscle stiffness, the danger exists of iatrogenic addiction to muscle relaxants such as diazepam (which is not particularly useful in this condition). If patients are treated with the medications listed in this article or with other medications, they should be educated about the drugs’ adverse effects. (See Treatment and Medication.)
Prior to the discovery of the specific gene defect in SJS, the syndrome’s similarity to myotonic disorders provoked speculation that a muscle ion channel abnormality or a muscle enzyme defect might underlie this condition. The fact that a defect exists in the gene for perlecan, a heparin sulfate proteoglycan that is the major proteoglycan of basement membranes and is present in cartilage, supports the general concept of a membrane abnormality and the presence of dysmorphic features.
However, precise knowledge as to why abnormal electrical discharges occur is still lacking. Perhaps the perlecan abnormality produces secondary membrane channel abnormalities. In addition, how this basement membrane defect actually causes the skeletal and other morphologic problems is not understood.
No evidence indicates that the muscle pathology in Stuve-Wiedemann syndrome is similar to that in SJS type I, although the muscles are probably not normal. Abnormal accumulations of lipid droplets have been found in the muscles of persons with Stüve-Wiedemann syndrome,  although what this means remains unclear.
Genetics of SJS type I
A multinational collaboration of scientists localized the gene defect for type I SJS to the 1p34-p36 region of chromosome 1.  Further research showed that the specific gene affected was the gene for perlecan, which is a heparin sulfate proteoglycan, the major proteoglycan of basement membranes.  It is also involved in cartilage. The gene encoding for perlecan is called HSPG2. Nicole et al described 3 families with a mutation in the HSPG2 gene.
Although SJS types IA and IB both involve a mutation of the perlecan gene, type IB is a more severe condition and, therefore, is usually diagnosed earlier than type IA.
One factor that has impeded the further understanding of SJS type I is that until the early 21st century, very few patients had been studied genetically. Through 2005, only 8 patients from 6 families had been reported in molecular genetic studies.
Stum et al made a major addition to this literature with a molecular genetic study of 35 patients in 23 families, finding 22 new mutations.  Most mutations were private (ie, limited to one particular family). Thus, no existence of a founder effect was suggested, whereby all (or a large percentage) of mutations could be presumed to derive from a single original case. The mutations included insertions and deletions and splice-site, missense, and nonsense mutations. Most of the mutations allowed for some level of functional protein production.
Often, a given patient has 2 different types of mutations, 1 of which allows a greater production of functional perlecan protein than the other. Based on the cases studied molecularly thus far, some level of functional perlecan protein production always seems apparent. Indeed, through alternative splicing, the normal protein may actually be produced, albeit at a lower level than normal.
In other cases, a functional, but somewhat abnormal, protein may be produced. Alternatively, a combination of different variants of perlecan could be produced, although at lower levels of functional protein than normal. Thus, a significant amount of molecular heterogeneity exists, genomically and proteomically, within SJS type I.
One would like to think that the molecular heterogeneity could explain the clinical heterogeneity, especially the existence of types IA and IB. In other words, it might be plausible that in type IA, more normal, or at least more functional, protein is available than in type IB. So far, however, that has not been shown.
In addition, no correlation has yet been found between the specific mutations found and the specific features of a given case. However, the findings by Stum et al should be important tools to help find correlations among genetic variants, perlecan forms and levels, and clinical subtypes. Of course, other facts yet unknown also may influence the severity and the specific characteristics of the disease.
Although the mutations discovered by Stum et al do not immediately provide an explanation for the specific character of the problems found in SJS (ie, the electrical membrane instability of the muscle, the specific dysmorphic features), now that many mutations are known, this knowledge can be a basis for future structural and functional correlations to better understand how the perlecan abnormalities cause the features of the disease and, perhaps, to find ways of ameliorating, or even curing, SJS.
A study by Rodgers et al questioned the concept that the C1532 mutation is the sole causative factor in SJS. The investigators developed perlecan knock-in mice to model SJS. The authors suggested that the transcriptional changes leading to perlecan reduction may represent the disease mechanism for SJS. 
A study by Stum et al concluded that partial endplate acetylcholinesterase (AChE) deficiency may contribute to muscle stiffness.  However, this deficiency was not associated with spontaneous activity at rest on EMG in the diaphragm, suggesting that there are additional factors that are required to generate the activity seen in SJS.
Dyssegmental dysplasia of the Silverman-Handmaker type
An additional point of interest related to perlecan is that another disease, called dyssegmental dysplasia of the Silverman-Handmaker type (DDSH), is also caused by a recessive mutation of the perlecan gene.  This disease is even rarer than SJS or Stuve-Wiedemann syndrome, and even fewer cases have been studied molecularly.
In the few patients who have been studied, mutations that totally eliminate the ability to produce any functional protein product (ie, functionally null mutations) have been discovered. Therefore, whereas in SJS types IA and IB some level of functional (and often even normal) perlecan protein is always produced, in DDSH, none is produced.
Conceptually, one could argue that DDSH is a third form of SJS type I (eg, type IC)—the worst type. However, it is considered a separate disease for several reasons.
The dysplasia has a segmental quality characterized by significant variations in the shape and size of the vertebral bodies (anisospondyly). This is considered a defect in segmentation during development. This feature has been viewed as making it part of a possible spectrum of dyssegmental disorders, which would include another poorly understood condition, Rolland-Desbuquois type of dyssegmental dwarfism  ; this disorder is similar to, but somewhat less severe than, DDSH.
The dyssegmental dwarfisms also manifest cleft palate and encephalocele, which are not features of SJS. Although the short stature of patients with SJS implies some degree of shortness of limbs, SJS patients do not exhibit the marked limb shortness (micromelia) seen in dyssegmental dwarfism.
The issue of whether DDSH is a separate disease is to some extent a question of classification, which could change if more fully studied clinical cases become available. For example, if mutations are found that produce levels of functional perlecan intermediate between those of SJS types I and DDSH and if the phenotype of such patients is also intermediate between the 2, then considering them the same disease and just part of a spectrum dependent on the level of expression of functional perlecan would probably be justified.
However, no cases of the Rolland-Desbuquois type of dyssegmental dwarfism have been examined for perlecan mutations or for levels of functional perlecan protein expression.
Genetics of SJS type II
SJS type II is not caused by the same genetic abnormality as SJS type I. The diseased gene in type II has been mapped to band 5p13.1, at locus D5S418.  By studying the genetic material of 19 patients who had been diagnosed with either Stuve-Wiedemann syndrome or SJS type II, investigators found that all patients had null mutations in their LIFR gene at the above-mentioned locus. This impaired the function of the JAK/STAT3 signaling pathway. Although the exact mutation was not identical in all 19 patients, the fact that the mutations all appeared to have the same molecular biologic and biochemical effect led to the conclusion that Stuve-Wiedemann syndrome and SJS type II should be considered a single, homogeneous disease.
SJS types IA and IB are very rare in the United States, although the exact frequency of these disorders is not known. Stuve-Wiedemann syndrome is even rarer. Although SJS was initially described in the United States, it has also been reported internationally, but as in the United States, SJS type I and Stuve-Wiedemann syndrome are rare throughout the world.
SJS syndrome has been described in males and females. However, data are insufficient to indicate any sexual predilection. Because SJS is an inherited disease, it is genetically present from conception. It is usually noticeable by the first year of life and frequently can be diagnosed at or soon after birth.
Except for the patients with Stuve-Wiedemann syndrome, which is fundamentally a different disease from SJS type I, most patients with SJS have a good prognosis. Muscle stiffness, muscle weakness, and skeletal abnormalities may worsen gradually or remain essentially stable.
Morbidity and mortality
SJS type IA does not significantly shorten lifespan. No definite data exist on whether this is also true for type IB shortens lifespan. Type II definitely shortens lifespan, with most patients not surviving to adulthood.
Much of the morbidity of SJS types IA and IB is related to the discomfort associated with the muscle stiffness and to problems with blepharospasm. As many as 20% of affected patients are mentally retarded. However, many patients are of normal or even superior intelligence. Skeletal abnormalities and other physical deformities may cause psychological morbidity in some individuals. Like a number of other myopathies, SJS is associated with an increased risk of malignant hyperthermia.
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