Weill-Marchesani syndrome: natural history and genotype-phenotype correlations from 18 news cases and review of literature.

BACKGROUNDWeill-Marchesani syndrome (WMS) belongs to the group of acromelic dysplasias, defined by short stature, brachydactyly and joint limitations. WMS is characterised by specific ophthalmological abnormalities, although cardiovascular defects have also been reported. Monoallelic variations in are associated with a dominant form of WMS, while biallelic variations in , and are responsible for a recessive form of WMS.OBJECTIVENatural history description of WMS and genotype-phenotype correlation establishment.MATERIALS AND METHODSRetrospective multicentre study and literature review.INCLUSION CRITERIAclinical diagnosis of WMS with identified pathogenic variants.RESULTS61 patients were included: 18 individuals from our cohort and 43 patients from literature. 21 had variants in , 19 in , 19 in and 2 in . All individuals presented with eye anomalies, mainly spherophakia (42/61) and ectopia lentis (39/61). Short stature was present in 73% (from -2.2 to -5.5 SD), 10/61 individuals had valvulopathy. Regarding variants, patients with a variant located in transforming growth factor (TGF)-β-binding protein-like domain 5 (TB5) domain were significantly smaller than patients with variant outside TB5 domain (p=0.0040).CONCLUSIONApart from the ophthalmological findings, which are mandatory for the diagnosis, the phenotype of WMS seems to be more variable than initially described, partially explained by genotype-phenotype correlation.KEYWORDSfractures, cartilage, genetics, medical, human genetics, mutation, phenotype© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.