Schwartz-Jampel Syndrome, Type 1

A number sign (#) is used with this entry because of evidence that Schwartz-Jampel syndrome type 1 (SJS1) is caused by mutation in the gene encoding perlecan (HSPG2; 142461) on chromosome 1p36.

See also Silverman-Handmaker type of dyssegmental dysplasia (DDSH; 224410), an allelic disorder with a more severe phenotype.

Neonatal Schwartz-Jampel syndrome type 2 (SJS2; 601559), also known as Stuve-Wiedemann syndrome (STWS), is a genetically distinct disorder with a more severe phenotype caused by mutation in the LIFR gene (151443) on chromosome 5p13.

Clinical Features

Aberfeld et al. (1965) described brother and sister with an apparently progressive disorder characterized by short stature, myotonic myopathy, dystrophy of epiphyseal cartilages, joint contractures, blepharophimosis, unusual pinnae, myopia, and pigeon breast. The same sibs had previously been reported by Schwartz and Jampel (1962), who focused attention on the blepharophimosis. See Aberfeld et al. (1970) and Aberfeld (1979). Mereu et al. (1969) described affected brother and sister with unrelated parents. Huttenlocher et al. (1969) described affected brother and sister with abnormally low muscle potassium. Procainamide therapy helped muscle function. The authors postulated a membrane defect with inability to maintain a proper gradient of sodium and potassium.

Van Huffelen et al. (1974) found myotonic EMG abnormalities in both parents and a sib of their patients with SJS. Pavone et al. (1978) also found EMG abnormalities in the mother of their 2 patients. Moodley and Moosa (1990) reported the syndrome in 3 South African children, 1 of whom did not have myotonia. They suggested that the absence of myotonia may be more frequent than is suggested by the literature.

Pinto-Escalante et al. (1997) described female monozygotic twins with Schwartz-Jampel syndrome. Minor physical differences were found in the affected toes and joints. Both patients also showed severe microcephaly and previously undescribed x-ray manifestations: a small skull, disproportion between skull and facial structures, and dysharmonic bone maturation. This was said to be the first reported instance of identical twins with this disorder.

Giedion et al. (1997) tentatively identified 3 types of SJS: type 1A, type 1B, and type 2 (601559), based on the clinical and radiologic findings of 81 patients reported in the literature as well as 5 of their own. SJS type 1A is usually recognized in childhood and has moderate bone dysplasia. The original descriptions of Schwartz and Jampel (1962) and Aberfeld et al. (1965) correspond to type 1A. SJS type 1B is similar to type 1A but recognizable at birth with more pronounced bone dysplasia resembling Kniest dysplasia (156550). SJS type 2 is manifest at birth with increased mortality and bone dysplasia resembling Pyle disease.

Spranger et al. (2000) described 4 patients, previously described as examples of micromelic chondrodysplasia resembling Kniest dysplasia (Stevenson, 1982), kyphomelic dysplasia (see 211350), or Burton syndrome (see 245160), in whom further evaluation and linkage analysis supported the diagnosis of Schwartz-Jampel syndrome. The authors concluded that SJS should be suspected in neonates with Kniest-like chondrodysplasia, congenital bowing of shortened femora and tibiae, and facial manifestations consisting of a small mouth, micrognathia, and possibly pursed lips. Differentiation from Stuve-Wiedemann syndrome is important because STWS is associated with high mortality.

Other Features

Viljoen and Beighton (1992) gave an extensive description of SJS and pointed out that malignant hyperthermia is a potentially lethal complication during anesthesia.

Stephen and Beighton (2002) reported difficulty in tooth extraction and orthodontic care due to small oral aperture and rigidity of the temporomandibular joints in a boy with Schwartz-Jampel syndrome. General anesthesia was hazardous because of a propensity to malignant hyperthermia, and endotracheal intubation was difficult because of shortness and rigidity of the neck and the small size of the laryngeal structures. Radiologic demonstration of dentigerous cysts represented a previously unreported observation in this disorder.

Inheritance

Beighton (1973) reported 2 offspring of a second-cousin marriage who had Schwartz-Jampel syndrome. Ferrannini et al. (1982) reported 2 brothers with Schwartz-Jampel syndrome. A sister, mother, and maternal grandmother showed less severe signs, suggesting either autosomal dominant inheritance or heterozygote manifestation.

Mapping

Using homozygosity mapping, Nicole et al. (1995) localized the SJS locus to chromosome 1p36.1-p34 in an 8-cM interval flanked by markers D1S199 and D1S234. Families of different ethnic backgrounds (Tunisia and South Africa) showed genetic linkage to the same locus. Moreover, 1 Algerian family also demonstrated evidence of genetic linkage to 1p36.1-p34.

Molecular Genetics

In affected members of 3 families with SJS1, Nicole et al. (2000) identified homozygous mutations in the HSPG2 gene (see, e.g., 142461.0001; 142461.0002).

Stum et al. (2006) identified 25 different HSPG2 mutations, including 22 novel mutations, distributed throughout the gene among 35 patients from 23 families with SJS1. Analysis of HSPG2 mRNA and perlecan immunostaining in patients' fibroblasts showed a hypomorphic, loss-of-function effect. No founder mutations were identified and no genotype/phenotype correlations were observed.

In the patient reported by Stevenson (1982) and Spranger et al. (2000), Arikawa-Hirasawa et al. (2002) identified a 7-kb deletion in the HSPG2 gene (142461.0010).

History

Pascuzzi et al. (1990) described the disorder in father and son and suggested autosomal dominant inheritance; Spaans (1991) commented that either pseudodominance or uniparental disomy might apply in that case. However, Giedion et al. (1997) postulated that the disorder described by Pascuzzi et al. (1990) was not SJS.