Spondyloepiphyseal Dysplasia, Maroteaux Type

A number sign (#) is used with this entry because of evidence that the Maroteaux type of spondyloepiphyseal dysplasia is caused by heterozygous mutation in the TRPV4 gene (605427).

Clinical Features

Doman et al. (1990) used the designation spondyloepiphyseal dysplasia (SED) of Maroteaux for a form of spondyloepiphyseal dysplasia with manifestations limited to the musculoskeletal system and with other features distinguishing it from Morquio syndrome of any type (253000, 253010, 252300), X-linked SED tarda (313400), brachyolmia (113500, 271530, 271630), and spondylometaphyseal dysplasia of Kozlowski (184252). Doman et al. (1990) reported affected father and son, aged 51 and 20 years, respectively, and affected mother and son. The patients were considered normal at birth. Platyspondyly is a feature, but there is no tongue-like deformity of the vertebral bodies in this disorder. Intelligence is normal and there is no clouding of the cornea or mucopolysacchariduria. Both hands and feet are short and stubby. The pelvic inlet is described as having a champagne-glass configuration, unlike the wine-glass-like configuration of the pelvic inlet in patients who have Morquio syndrome. Odontoid hypoplasia was not found. Genu valgum was present.

Nishimura et al. (2003) reported a Japanese mother and son and an unrelated 65-year-old man with spondyloepiphyseal dysplasia of Maroteaux. The adults had extremely short stature, brachydactyly, platyspondyly, rectangular vertebral bodies with irregular endplates, epiphyseal hypoplasia of the large joints, and iliac hypoplasia. The man had myeloradiculopathy necessitating neurosurgery. The affected child had short stature and brachydactyly with characteristic spine radiographic findings. None of the patients had mutations in the COL2A1 gene (120140), which excluded a diagnosis of spondyloperipheral dysplasia (271700). Nishimura et al. (2003) suggested that platyspondyly and brachydactyly are much more severe in SED of Maroteaux than in spondyloperipheral dysplasia.

Megarbane et al. (2004) reported a patient with characteristic features of spondyloepiphyseal dysplasia of Maroteaux. The 11-year-old girl, who was of normal intelligence, was the only child of nonconsanguineous parents, and appeared normal at birth. Clinical features included short stature, head positioned in hyperextension, mild arched palate, prominent joints, limited elbow movements, hyperextensible wrists and fingers, brachydactyly, broad thorax, pectus carinatum, short trunk, genu valgum, and flat feet. A radiographic skeletal survey revealed generalized osteoporosis, platyspondyly, thoracic kyphoscoliosis, small and square iliac wings, short femoral necks, dysplastic epiphyses, flared metaphyses, and brachydactyly with various carpal, metacarpal, and finger malformations. Megarbane et al. (2004) reviewed features of the 6 previously reported cases and noted that their patient's cervical spine instability and distal joint laxity were unusual, indicating clinical or genetic heterogeneity.

Molecular Genetics

Nishimura et al. (2010) analyzed the candidate gene TRPV4 (605427) in 6 patients with the Maroteaux type of SED, including 3 previously reported patients (Nishimura et al., 2003; Megarbane et al., 2004), and identified heterozygous mutations in all of them (see, e.g., 605427.0007 and 605427.0018-605427.0021). Nishimura et al. (2010) noted that SED Maroteaux type is thus allelic to several other skeletal dysplasias also caused by heterozygous mutation in TRPV4, including brachyolmia type 3 (113500), spondylometaphyseal dysplasia Kozlowski type (SMDK; 184252), and metatropic dysplasia (MD; 156530), and that the 4 skeletal disorders share many radiographic features, particularly platyspondyly with broad and elongated vertebral bodies that overshadow the vertebral pedicles in anteroposterior radiographs. However, brachydactyly is usually absent or very mild in SMDK, and kyphosis and/or scoliosis develops in childhood in MD but is not seen in patients with the Maroteaux type of SED. Nishimura et al. (2010) noted that genotype/phenotype correlations did not appear to be robust, and suggested that in the presence of a TRPV4 mutation, modulation of the clinical phenotype by other genes and/or by nongenetic factors might occur.