Biallelic Variants in MIMS1 Produce a Form of Spondyloepimetaphyseal Dysplasia With Tracheal Stenosis and Ectodermal Dysplasia ( SEMDTSED )

Through the GeneMatcher data-sharing database, we identified five affected individuals from four unrelated families with a skeletal dysplasia who have biallelic, putatively deleterious variants in MIMS1 (formerly FAM210A). The common features included chondrodysplasia with short stature, tracheal stenosis, conical teeth and/or early tooth decay, and sparse hair suggestive of ectodermal dysplasia as a component of the phenotype. The radiographic features included platyspondyly, epiphyseal dysplasia of the long bones, short phalanges with delayed carpal ossification, lacy iliac crests, and calcaneal spurs, consistent with a form of spondyloepimetaphyseal dysplasia. Missense variants clustered within the conserved DUF1279 domain of MIMS1, while one family harbored compound heterozygous nonsense variants, collectively supporting a loss-of-function mechanism. According to the dyadic naming convention in the latest Nosology of Genetic Disorders of Bone, we suggest the name of "Spondyloepimetaphyseal dysplasia with tracheal stenosis and ectodermal dysplasia (SEMDTSED), MIMS1-related."