Background: Weill-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 FBN1 are associated with a dominant form of WMS, while biallelic variations in ADAMTS10, ADAMTS17 and LTBP2 are responsible for a recessive form of WMS.
Objective: Natural history description of WMS and genotype-phenotype correlation establishment.
Materials and methods: Retrospective multicentre study and literature review.
Inclusion criteria: clinical diagnosis of WMS with identified pathogenic variants.
Results: 61 patients were included: 18 individuals from our cohort and 43 patients from literature. 21 had variants in ADAMTS17, 19 in FBN1, 19 in ADAMTS10 and 2 in LTBP2. 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 FBN1 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 FBN1 variant outside TB5 domain (p=0.0040).
Conclusion: Apart 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.
Keywords: fractures, cartilage; genetics, medical; human genetics; mutation; phenotype.
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