Floating-Harbor syndrome (FLHS) is a rare neurodevelopmental and skeletal disorder caused by truncating variants in exons 33 and 34 of the SRCAP gene. It is characterized by distinctive facial features, delayed bone age, short stature, and moderate intellectual disability. While digital anomalies have been reported in approximately half of the more than 100 known cases, the phenotypic spectrum continues to expand. Here, we describe a family in which two individuals were identified with FLHS. Both the proband and her mother presented with typical manifestations, including classic facial dysmorphism, short stature, intellectual disability, brachydactyly, and clinodactyly. Moreover, the proband exhibited a novel combination of polydactyly and syndactyly affecting the right fifth and sixth toes, a feature previously unreported in FLHS. Additionally, she had complications including anemia, feeding difficulties, recurrent infections, epilepsy, and thrombosis. Whole-exome sequencing identified a heterozygous SRCAP c.7330CT (p.Arg2444Ter) mutation in both affected individuals. The proband also harbored compound heterozygous mutations in MMACHC (c.609GA/p.Trp203Ter and c.565CT/p.Arg189Cys), potentially explaining some extra-skeletal symptoms. In summary, this study describes the first case of FLHS concurrently presenting with both polydactyly and syndactyly. Our work broadens the known phenotypic range of this rare syndrome.
Tang et al. (Tue,) studied this question.