DMRT2 – Spondylocostal Dysostosis

Spondylocostal dysostosis is a rare autosomal recessive disorder characterized by vertebral segmentation defects, rib malformations, scoliosis, and short stature. We report a single male neonate with severe rib anomalies (missing, fused, bifid, and hypoplastic ribs), vertebral malformations, mild scoliosis, and respiratory insufficiency in whom a homozygous start-loss variant in DMRT2, c.1A>T (p.Met1Leu), was identified (PMID:29681102). This variant, absent from population databases, has not been previously associated with SCD. No additional affected relatives were available for segregation analysis.

Loss of DMRT2 function is supported by murine studies: Dmrt2 knock-out mice develop severe rib and vertebral defects strikingly overlapping the human phenotype (PMID:29681102). These data indicate a loss-of-function mechanism consistent with haploinsufficiency. Overall, the current evidence—one proband with a homozygous LoF variant and concordant animal model—supports a Limited clinical validity for DMRT2 in SCD. Further case series and segregation studies are needed to elevate confidence. Key take-home: DMRT2 LoF variants likely define a novel autosomal recessive SCD subtype primarily marked by severe rib malformations.

References

• American journal of medical genetics. Part A | 2018 | Homozygous DMRT2 variant associates with severe rib malformations in a newborn. PMID:29681102

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