Dyggve–Melchior–Clausen syndrome: novel splice mutation with atlanto-axial subluxation

Abstract

Dyggve-Melchior-Clausen (DMC) syndrome is a rare autosomal recessive disorder characterized by the association of a progressive spondyloepimetaphyseal dysplasia and mental retardation ranging from mild to severe. The disorder results from mutations in the dymeclin (DYM) gene in the 18q12-12.1 chromosomal region. We report two siblings with classical clinical and radiological features of DMC and asymptomatic atlanto-axial dislocation. A novel homozygous splice-site mutation (IVS15+3G>T) was detected. Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed that this mutation affects normal splicing. To the best of our knowledge, this is the first report of DMC from Saudi Arabia. The splice mutation noted in our patients was compared to the previously reported cases and supports the hypothesis that loss of DYM function is the likely mechanism of disease pathogenesis. In conclusion, distinction between this type of skeletal dysplasia and Morquio disease (MPS IV) is important for paediatricians and clinical geneticist in providing standard patient care and genetic counselling.

Additional three patients with Smith‐McCort dysplasia due to novel RAB33B mutations

“…Analyses for patients with SMC and DMC revealed linkage to loci on chromosome 18q12 and then mutations in DYM gene in both disorders [Ehtesham et al, ; El Ghouzzi et al, ; Ahmad et al, ]. Till date, 46 patients from 30 families with DMC and 8 patients from 3 families with SMC were reported with a mutation in DYM [Burns et al, ; Cohn et al, ; El Ghouzzi et al, ; Paupe et al, ; Kinning et al, ; Pogue et al, ; Neumann et al, ; Santos et al, ; Denais et al, ; Khalifa et al, ]. However, mutations in another gene, RAB33B , are also known to cause SMC and until now only five patients from two families have been reported with mutations in this gene [Alshammari et al, ; Dupuis et al, ].…”

Atlantoaxial instability treated with posterior atlantoaxial fixation in two siblings with dyggve-melchior-clausen syndrome.

“…Skeletal abnormalities of the pelvis, hip and spinal column are common findings. Odontoid hypoplasia and atlantoaxial instability have been infrequently reported as components of the DMC syndrome (4,11,12). We report the rare association of odontoid hypoplasia and atlantoaxial instability in two siblings with DMC syndrome.…”

“…Only 3 cases have been reported in the Indian subcontinent (4,10). The syndrome is more commonly seen in Lebanon, Greenland, Egypt and Morocco (1,11,12). The hallmarks of the syndrome are progressive spondyloepimetaphyseal dysplasia and mild to severe mental retardation.…”

“…The syndrome is often misdiagnosed as Morquoi's syndrome due to resemblance of its clinical presentation. The absence of corneal clouding, mental retardation, deafness and cardiac abnormalities differentiate Morquoi's syndrome from DMC syndrome (1,4,(10)(11)(12). The characteristic clinical manifestation of DMC syndrome include short -trunk dwarfism, coarse facies, barrel shaped thorax, microcephaly and rhizomelic limb shortening.…”

A 14‐year‐old girl with Smith‐McCort dysplasia misdiagnosed as seronegative juvenile idiopathic arthritis

“…Orthopedic complications include possible spinal cord compression due to atlantoaxial instability, scoliosis, thoracic kyphosis, subluxation of the hips, deformations of the knees and restricted joint mobility. The musculature is poorly developed 1,5–7 …”