Background: Floating-Harbor Syndrome (FHS) is an exceptionally rare autosomal dominant disorder caused by heterozygous pathogenic variants in SRCAP. Approximately 100 cases have been reported worldwide, and the phenotypic spectrum is still evolving. Case Presentation: We present two unrelated boys who were diagnosed at the same centre and were found to carry the same heterozygous nonsense variant in SRCAP (c.7330C>T; p.Arg2444*). The first patient was diagnosed following whole-exome sequencing after years of being investigated for short stature, cognitive impairment, expressive language delay, and craniofacial dysmorphisms. The second patient’s diagnosis was prompted by his striking resemblance to the first patient, which serves as a reminder of the importance of phenotypic observation in diagnosis. Both cases displayed the classical triad of FHS: proportionate short stature with delayed bone age, expressive language delay and distinctive craniofacial morphology as well as cognitive impairment. Additionally, less frequently reported manifestations included irregular shape of the fingers, brachydactyly, and broad fingertips with prominent fetal pads, dysplastic nails, posteriorly rotated ears, and low-set posterior hairline. This expands the known phenotype for this variant. Longitudinal follow-up revealed persistent expressive language deficits and evolving musculoskeletal features. Conclusion: These cases highlight the importance of combining genomic testing with careful phenotypic analysis in rare syndromes. They enhance genotype–phenotype correlations for SRCAP-related FHS and demonstrate how one diagnosis can shed light on another.
Carvalho et al. (Thu,) studied this question.