A novel frameshift mutation and infrequent clinical findings in two cases with Dyggve-Melchior-Clausen syndrome

Clin Dysmorphol. 2014 Jan;23(1):1-7. doi: 10.1097/MCD.0000000000000020.

Abstract

Dyggve-Melchior-Clausen syndrome (DMC) (MIM #223800) is a rare autosomal-recessive type of skeletal dysplasia accompanied by variable degrees of intellectual disability (ID). It is characterized by progressive spondyloepimetaphyseal dysplasia leading to disproportionate short stature, microcephaly, and coarse facies. The radiographic appearance of generalized platyspondyly with double-humped end plates and the lace-like appearance of iliac crests are pathognomonic in this syndrome. The disorder results from mutations in the dymeclin (DYM) mapped to the 18q12-12.1 chromosomal region. Here, we report two cases with DMC: one with disproportionate short stature, developmental delay, and severe ID with a novel frameshift mutation (c.1028_1056del29) leading to a premature stop codon, and the second patient with classical clinical and radiological features of DMC with mild ID and rectal prolapse, which is very rare. The clinical diagnosis was confirmed with molecular analysis of DYM with a known mutation at c.580C>T (p.R194X). The parents and sibling of the second patient were heterozygous carriers with mild skeletal changes and short stature.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Child, Preschool
  • Codon, Nonsense / genetics
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / pathology
  • Dwarfism / genetics*
  • Dwarfism / pathology
  • Female
  • Frameshift Mutation
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / pathology
  • Humans
  • Infant
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Intracellular Signaling Peptides and Proteins
  • Microcephaly / complications
  • Microcephaly / genetics
  • Microcephaly / pathology
  • Osteochondrodysplasias / congenital*
  • Osteochondrodysplasias / genetics
  • Osteochondrodysplasias / pathology
  • Proteins / genetics*

Substances

  • Codon, Nonsense
  • DYM protein, human
  • Intracellular Signaling Peptides and Proteins
  • Proteins

Supplementary concepts

  • Dyggve-Melchior-Clausen syndrome