Ehlers-Danlos Syndrome, Spondylodysplastic Type, 3

A number sign (#) is used with this entry because of evidence that Ehlers-Danlos syndrome spondylodysplastic type 3 (EDSSPD3) is caused by homozygous mutation in the zinc transporter gene SLC39A13 (608735) on chromosome 11p11.

Description

Ehlers-Danlos syndrome spondylodysplastic type 3 is characterized by short stature, hyperelastic skin and hypermobile joints, protuberant eyes with bluish sclerae, finely wrinkled palms, and characteristic radiologic features (Giunta et al., 2008).

For a discussion of genetic heterogeneity of the spondylodysplastic type of Ehlers-Danlos syndrome, see 130070.

Clinical Features

Giunta et al. (2008) described a 'spondylocheiro dysplastic form of Ehlers-Danlos syndrome' in 6 patients from 2 consanguineous families. Clinical features included postnatal growth retardation, moderate short stature, protuberant eyes with bluish sclerae, hands with finely wrinkled palms, atrophy of the thenar muscles, and tapering fingers. Patients had thin, hyperelastic skin and hypermobile small joints consistent with an Ehlers-Danlos-like phenotype. Radiologic features included mild to moderate platyspondyly, mild to moderate osteopenia of the spine, small ileum, flat proximal femoral epiphyses, short, wide femoral necks, and broad metaphyses (elbows, knees, wrists, and interphalangeal joints).

Biochemical Features

Giunta et al. (2008) found that all 6 patients with a spondylocheirodysplastic form of EDS had an increased lysyl pyridinoline/hydroxylysyl pyridinoline (LP/HP) ratio indicating underhydroxylation of collagen. The ratio in patients (mean 0.89 +/- 0.18) was lower than that in individuals with EDS VI (225400; mean 5.97 +/- 0.99) but markedly higher than that in controls (mean 0.19 +/- 0.02). Mass-spectral analysis of the alpha-1 (120150) and alpha-2 (120160) chains of type I collagen revealed underhydroxylation of lysyl and prolyl residues. In vitro activities of lysyl hydroxylase (153454) and prolyl 4-hydroxylase (176710) were normal.

Mapping

By a genomewide SNP scan and linkage analysis, Giunta et al. (2008) defined a 16.9-Mb critical region for SCD-EDS on chromosome 11 between markers D11S1779 and D11S4191 (combined maximum lod score of 5.3).

Molecular Genetics

In all 6 affected members of 2 families with spondylocheirodysplastic EDS, Giunta et al. (2008) identified homozygosity for a 9-bp in-frame deletion in exon 4 of the membrane-bound zinc transporter SLC39A13 (608735.0001).

Fukada et al. (2008) identified a homozygous loss-of-function mutation in the SLC39A13 gene (G74D; 608735.0002) in 2 sibs with an Ehlers-Danlos syndrome-like phenotype similar to that reported by Giunta et al. (2008).