Nosology of genetic skeletal disorders: 2023 revision

Abstract

The “Nosology of genetic skeletal disorders” has undergone its 11th revision and now contains 771 entries associated with 552 genes reflecting advances in molecular delineation of new disorders thanks to advances in DNA sequencing technology. The most significant change as compared to previous versions is the adoption of the dyadic naming system, systematically associating a phenotypic entity with the gene it arises from. We consider this a significant step forward as dyadic naming is more informative and less prone to errors than the traditional use of list numberings and eponyms. Despite the adoption of dyadic naming, efforts have been made to maintain strong ties to the MIM catalog and its historical data. As with the previous versions, the list of disorders and genes in the Nosology may be useful in considering the differential diagnosis in the clinic, directing bioinformatic analysis of next‐generation sequencing results, and providing a basis for novel advances in biology and medicine.

New pathogenic variant in DLX5: New clues for a clinical spectrum from split-hand-foot malformation to fibular aplasia, tibial campomelia and oligosyndactyly

“…FATCO syndrome forms part of the limb hypoplasia-reduction defects group of the Nosology of genetic skeletal disorders ( Unger et al, 2023 ), along with 41 other dysplasias, including Fanconi anemia (MIM 607139), Holt-Oram syndrome (MIM 142900), Split-hand-foot malformation with long bone deficiency (SHFLD, MIM 119100), Furhmann syndrome (MIM 228930) and Al-Awadi Raas-Rothschild limb-pelvis hypoplasia-aplasia (MIM 276820).…”

“…Although classified in different nosology groups ( Unger et al, 2023 ), phenotypic overlap of SHFM forms and FATCO have led to the suggestion of similar genetic background ( Bieganski et al, 2012 ), however, few molecular studies have been undertaken. The molecularly confirmed case described here validates this hypothesis.…”

Evolution of clinical and radiological presentations of spondyloepimetaphyseal dysplasia, RPL13‐related: Description of 11 further cases

“…Spondyloepimetaphyseal dysplasias (SEMD) are a heterogeneous group of rare skeletal dysplasias, with 32 different entities listed in the recent skeletal dysplasia nosology. 1 In 2013, a novel SEMD was described in two patients, characterized with severe disproportionate short stature, developing shortly after birth, platyspondyly with irregular vertebral bodies and central indentation of endplates, genu varum, coxa vara, bowed femurs and severe irregularities of the femoral epiphyses and metaphyses, mainly in the lower limbs. 2 Later, in 2019, heterozygous RPL13 variants were identified as the causative defect.…”

Expanding the phenotype of anauxetic dysplasia caused by biallelic NEPRO mutations: A case report

“…The cartilage hair hypoplasia and anauxetic dysplasia (CHH‐AD) spectrum comprises a group of rare autosomal recessive skeletal disorders with variable phenotypes. Recently, a revision was proposed by Unger et al (2023), classifying CHH‐AD into nosology group 11 (NOS 11). NOS 11‐0020 comprises metaphyseal dysplasia without hypotrichosis (MDWH, MIM #250460), cartilage hair hypoplasia (CHH, MIM #250250) and anauxetic dysplasia (ANXD) type 1 (ANXD1, MIM #607095), all of which have been associated with variants in the RMRP gene (Ridanpää et al, 2001; Thiel et al, 2005).…”