Spondyloepimetaphyseal Dysplasia, Di Rocco Type

A number sign (#) is used with this entry because of evidence that spondyloepimetaphyseal dysplasia of the Di Rocco type (SEMDDR) is caused by heterozygous mutation in the UFSP2 gene (611482) on chromosome 4q35. One such family has been reported.

Description

Spondyloepimetaphyseal dysplasia of the Di Rocco type (SEMDDR) is characterized by short stature, joint pain, and genu varum, as well as SEMD involving primarily the hips but also affecting the wrists, hands, knees, and ankles. Patients also exhibit variable degrees of metaphyseal and spine involvement (Di Rocco et al., 2018).

Clinical Features

Di Rocco et al. (2018) reported a 3-year-old Italian girl who was asymptomatic until the second year of life when she developed leg pain and a waddling gait. Examination at age 3 showed short stature and mild genu varum. X-rays showed absence of ossification nucleus of proximal femoral epiphysis; irregular profile of femur neck and acetabular roof; metaphyseal dysplasia of distal femur and proximal tibia; mild vertebral abnormalities, including slightly convex end plates of vertebral bodies and minimal hypoplasia of some vertebral bodies anteriorly; and delayed carpal bone age. No bone abnormalities were observed in the upper limbs. Her mother and maternal grandmother exhibited short stature and had waddling gait, bowlegs, and painful joints with restricted mobility from childhood, and both had undergone multiple orthopedic surgeries. X-rays in the mother had shown absence of femoral capital epiphysis, metaphyseal involvement of distal femur and proximal tibia, and slightly flattened vertebral bodies with defective ossification anteriorly. X-rays at age 38 showed osteoarthropathy in the wrists and shoulders, as well as progressive spine involvement, whereas the metaphyseal lesions of the knees were no longer detectable.

Molecular Genetics

By whole-exome sequencing in an Italian family with spondyloepimetaphyseal dysplasia, Di Rocco et al. (2018) identified heterozygosity for a missense mutation in the UFSP2 gene (D426A; 611482.0002) that segregated with disease and was not found in controls or in public variant databases.