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.
References
Carbonell P, Fernandez P, Vicete-Franqueira J (2005) MRI Findings in Dyggve–Melchior–Clausen syndrome, a rare spondyloepiphyseal dysplasia. J Magn Reson Imaging 22:572–576
Cohn D, Ehtesham N, Krakow D et al (2003) Mental retardation and abnormal skeletal development (Dyggve–Melchior–Clausen dysplasia) due to mutations in a novel, evolutionary conserved gene. Am J Hum Genet 72:419–428
Dimitrov A, Paupe V, Gueudry C et al (2009) The gene responsible for Dyggve–Melchior–Clausen syndrome encodes a novel peripheral membrane protein dynamically associated with Golgi apparatus. Hum Mol Genet 18:440–453
Dyggve HV, Melchior JC, Clausen J (1962) Morquio–Ulrich’s disease: an inborn error of metabolism? Arch Dis Child 37:525–534
El Ghouzzi V, Dagoneau N, Kinning E et al (2003) Mutations in a novel gene dymeclin (FLJ20071) are responsible for Dyggve–Melchior–Clausen syndrome. Hum Mol Genet 12:357–364
Girisha K, Cormier-Daire V, Heuertz S (2008) Novel mutation and atlanto-axial dislocation in two siblings from India with Dyggve–Melchior–Clausen syndrome. Eur J Med Genet 51:251–256
Hall-Craggs M, Chapman M (1987) Case report 431: Dyggve–Melchior–Clausen syndrome (DMCS). Skeletal Radiol 16:422–424
Kandziora F, Neumann L, Schnake K et al (2004) Atlanto-axial instability in Dyggve–Melchior–Clausen syndrome: case report and review of the literature. J Neurosurg 96(suppl 1):112–117
Kinning E, Tufarelli C, Winsip W et al (2005) Genomic duplication in Dyggve–Melchior–Clausen Syndrome, a novel mutation mechanism in an autosomal recessive disorder. J Med Genet 42:1–6
Naffah J, Taleb N (1974) Two further cases of Dyggve–Melchior–Clausen syndrome with hypoplasia of the odontoid apophysis and spinal compression. Arch Fr Pédiatr 31:985–992
Neumann LM, El Ghouzzi V, Paupe V et al (2006) Dyggve–Melchior–Clausen syndrome and Smith–McCort dysplasia: clinical and molecular findings in three families supporting genetic heterogeneity in Smith–McCort dysplasia. Am J Hum Genet 140A:421–426
Osipovich AB, Jenning JL, Lin Q et al (2008) Dyggve–Melchior–Clausen syndrome: chondrodysplasia resulting from defects in intracellular vesicle traffic. Proc Natl Acad Sci USA 105:16171–16176
Paupe V, Gilbert T, Le Merrer M et al (2004) Recent advances in Dyggve–Melchior–Clausen syndrome. Mol Genet Metab 83:51–59
Pogue R, Ehtesham N, Repetto G et al (2005) Probable identity-by-descent for a mutation in the Dyggve–Melchior–Clausen/Smith–McCort dysplasia (Dymeclin) gene among patients from Guam, Chile, Argentina, and Spain. Am J Med Genet 138:75–85
Schorr S, Legum C, Ochshorn M et al (1974) The Dyggve–Melchior–Clausen syndrome. Am J Roentgenol 128:107–113
Smith R, McCort J (1958) Osteochondrodystrophie (Morquio–Brailsford type). Calif Med 88:55–59
Spranger J, Bierbaum B, Herrmann J (1976) Heterogeneity of Dyggve–Melchior–Clausen dwarfism. Hum Genet 33:279–287
Thauvin-Robinet C, El Ghouzzi V, Chemaitilly W et al (2002) Homozygosity mapping of a Dyggve–Melchior–Clausen syndrome gene to chromosome 18q21.l. J Med Genet 39:714–717
Yunis E, Fontalvo J, Quintero L (1980) X-linked Dyggve–Melchior–Clausen syndrome. Clin Genet 18:284–290
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Khalifa, O., Imtiaz, F., Al-Sakati, N. et al. Dyggve–Melchior–Clausen syndrome: novel splice mutation with atlanto-axial subluxation. Eur J Pediatr 170, 121–126 (2011). https://doi.org/10.1007/s00431-010-1298-0
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DOI: https://doi.org/10.1007/s00431-010-1298-0