Dyggve-Melchior-Clausen syndrome in three siblings: a unique case series with dual diagnosis of Down syndrome and Hirschsprung disease.

OBJECTIVES: Dyggve-Melchior-Clausen (DMC) syndrome is a rare autosomal recessive skeletal dysplasia caused by mutations in the DYM gene. It is characterized by progressive spondyloepimetaphyseal dysplasia, short stature, coarse facial features, microcephaly and intellectual disability. While it clinically resembles Morquio syndrome (mucopolysaccharidosis type IV, MPS IV), DMC is distinguished by cognitive impairment, absence of corneal clouding, normal urinary glycosaminoglycans and distinctive radiological features.

CASE PRESENTATION: We reported three siblings with DMC syndrome. Two 4-year-old monozygotic male twins, born to consanguineous parents, presented with growth retardation and developmental delay. Radiographs showed generalized platyspondyly, rhizomelic shortening and metaphyseal dysplasia, while biochemical tests excluded MPS IV. Molecular tests revealed a homozygous deletion in exon 16 of the DYM gene. The third sibling, with Down syndrome, also exhibited similar skeletal features and carried the same DYM deletion.

CONCLUSIONS: The clinical and radiological features of our patients were consistent with DMC syndrome, with partial overlap with MPS IV. This case series represents the first reported coexistence of DMC and Down syndrome. In addition, we identified a novel homozygous deletion in exon 16 of the DYM gene, which broadens the known mutational spectrum. This finding also highlights the importance of comprehensive genetic testing when standard sequencing results are inconclusive. The presence of neurological findings, such as seizures, further supports the need for combined genetic and neurological evaluation in these patients.