Excerpt from Schwartz-Jampel Syndrome

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Background

Schwartz-Jampel syndrome (SJS) is a term now applied to 2 different autosomal recessive inherited 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. The most commonly recognized and described type is IA, which exhibits muscle stiffness, mild (and largely nonprogressive) muscle weakness, and a number of minor morphological abnormalities. In affected patients, 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. Types IB and type II (now known to be a separate disease more commonly referred to as Stuve-Wiedemann syndrome) are discussed in further detail later.

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 present the case of 2 siblings, a 6-year-old boy and a 3-and-a-half-year-old girl, who had the following clinical characteristics:

• 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 opined that the disease might represent a generalized problem with muscle and tendon development during infancy.

As mentioned above, certain subtypes of SJS are now recognized. Type IA is the classic type described by Schwartz and Jampel. Types IB and a type II have also been delineated. Type IA becomes apparent later in childhood and is less severe. Type IB is apparent immediately at birth and is more severe clinically, although typically compatible with life and even long-term survival. Types IA and IB derive from mutations of the same gene, the HSPG2 gene, which codes for perlecan, a heparin sulfate proteoglycan.

Type II, like type IB, is apparent immediately at birth. The patients look similar to those with type IB. However, it was 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.

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). A high infant mortality rate is associated with this condition. Long-term survivors are rare. However, 2 long-term survivors, ages 3 and 12 years, have recently been reported (Di Rocco, 2003). In addition to problems with bone dysplasia, these children also 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).

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 below pertains to SJS types IA and IB. Information pertinent to Stuve-Wiedemann syndrome will be identified as such. More genetic details of both diseases are provided in Causes.

Pathophysiology

The clinical features of muscle stiffness in SJS type I somewhat resemble those seen in myotonic disorders, stiff person syndrome, or 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).

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.

Prior to the discovery of the specific gene defect, the 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 of 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 morphological problems is not understood.

No evidence indicates that the muscle pathology in Stuve-Wiedemann syndrome is similar, although the muscles are probably not normal. Abnormal accumulations of lipid droplets have been found in the muscles of persons with Stuve-Wiedemann syndrome (Di Rocco, 2003), although what this means remains unclear.

Frequency

United States

SJS types IA and IB are very rare, but the frequency is not actually known. Stuve-Wiedemann syndrome is probably even rarer.

International

Although SJS was initially described in the United States, it has also been reported internationally. Both SJS type I and Stuve-Wiedemann syndrome are rare throughout the world

Mortality/Morbidity

• SJS type IA does not significantly shorten lifespan. No definite data exist on whether 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.

Race

No significant information is available on racial distribution.

Sex

SJS syndrome has been described in both males and females. However, data are insufficient to indicate any sexual predilection.

Age

SJS is an inherited disease and, thus, 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.

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