Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene: Double‐layer patella as a reliable sign

Abstract

Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene result in a family of skeletal dysplasias, which comprise lethal (achondrogenesis type 1B and atelosteogenesis type 2) and non-lethal conditions (diastrophic dysplasia and recessive multiple epiphyseal dysplasia (rMED)). The most frequent mutation is R279W, which in a homozygous state results in rMED with bilateral clubfoot, MED, and "double layered" patella. We describe three patients with rMED caused by a previously unreported homozygous mutation in the DTDST gene. The three patients (from two families) were born to healthy, non-consanguineous parents. All developed signs of hip dysplasia in early childhood and two had episodes of recurrent patella dislocation. Two underwent bilateral total hip replacements at ages 13 and 14 years. The feet, external ears, and palate were normal. Stature was normal in all cases. Radiographs showed dysplastic femoral heads, mild generalized epiphyseal dysplasia, abnormal patella ossification, and normal hands and feet. Direct sequence analysis of genomic DNA demonstrated a homozygous 1984T > A (C653S) change in the DTDST gene in all patients. The clinically normal parents were heterozygous for the change. This is the first description of a homozygous C653S mutation of the DTDST gene. Hip dysplasia and patella hypermobility dominates the otherwise mild phenotype. These patients further expand the range of causative mutations in the DTD skeletal dysplasia family.

Double-layered patella in multiple epiphyseal dysplasia is not exclusive toDTDST mutation

“…Double-layered patella is not likely to be a mere abnormal ossification pattern, but is a true anatomic variant, with two ossification centers instead of one. Makitie et al [2003] reported three patients from two families with recessive MED and homozygous DTDST mutation (C653S). All three patients had a double-layered patella.…”

Mutations in the known genes are not the major cause of MED; distinctive phenotypic entities among patients with no identified mutations

“…Taking together with the previously reported mutations, 10,14,15,18,19 Figure 5 Patient 16 was diagnosed with MED in early childhood. At 10 years he was asymptomatic but had genua vara, increased lumbar lordosis, short stature (o3%) and generalized joint laxity.…”

“…Detailed clinical and mutation data have been reported previously for four of these patients. Three of these patients with clinical findings consistent with rMED had homozygous DTDST mutations; 14,15 one had radiographic findings typical of EDM1 and was found to have a COMP mutation. 18 Of the remaining 26 patients, 25 consented to participate in the study.…”

“…Patients with MATN3 mutations present with features partially overlapping with MED caused by COMP and collagen IX mutations, 19 but may be differentiated from these by a careful assessment of their skeletal radiographs. As in the other forms of MED, 6,15 however, there may exist a 'window of opportunity' in mid-childhood for differentiating these forms from each other, since the radiographic findings become less characteristic towards closure of the growth plates. Arg 718 Trp 9 and Ala 735 Val (this study) mutations in C-terminus of COMP seem to associate with myopathic symptoms which are similar to those seen in patients with a COL9A3 mutation.…”

Bipartite Tibial Epiphysis: Radiologic and Arthroscopic Presentation

“…Most bipartite bones represent incidental findings and are asymptomatic, but cases of painful bipartite ossification have been reported [3,9,13,14,19]. Moreover, some authors have studied the relationship of bipartite bones with some genetic mutations and diastrophic dysplasia [5,11,17].…”