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Floating-Harbor syndrome (FHS) is a rare autosomal dominant genetic disorder characterized by proportionate short stature with delayed bone maturation, lack of expressive language, and distinctive facial features including a large nose, long eyelashes, deeply set eyes, and triangular face. Mutations in the SRCAP gene cause truncated SNF2-related CREBBP activator protein (SRCAP) and lead to FHS. SRCAP is one of several proteins that act as coactivator for the CREB-binding protein which is associated with Rubinstein-Taybi syndrome (RSTS). This condition likely explains the phenotypic overlap between FHS and RSTS. Herein, we report on a patient with FHS who also had dystrophic toenails, preauricular skin tag, and nasolacrimal duct obstruction which is also defined in patients with RSTS. In summary, the fact that especially nasolacrimal duct obstruction has also been observed in RSTS reinforces the idea that this finding is one of the features of FHS. Assessment of the lacrimal system and examination of skin and nails should be suggested in patients with FHS.

Floating-Harbor syndrome is a rare autosomal dominant genetic disorder associated with SRCAP mutation. To date, approximately 50 cases of Floating-Harbor syndrome have been reported, but none have been reported in Korea yet. Floating-Harbor syndrome is characterized by delayed bony maturation, unique facial features, and language impairment. Here, we present a 6-year-old boy with a triangular face, deep-set protruding eyes, low-set ears, wide nose with narrow nasal bridge, short philtrum, long thin lips, clinodactyly, and developmental delay that was transferred to our pediatric clinic for genetic evaluation. He showed progressive delay in the area of language and cognition-adaption as he grew. He had previously undergone chromosomal analysis at another hospital due to his language delay, but his karyotype was normal. We performed targeted exome sequencing, considering several syndromes with similar phenotypes. Library preparation was performed with the TruSight One sequencing panel, which enriches the sample for about 4,800 genes of clinical relevance. Massively parallel sequencing was conducted with NextSeq. An identified variant was confirmed by Sanger sequencing of the patient and his parents. Finally, the patient was confirmed as the first Korean case of Floating-Harbor syndrome with a novel SRCAP (Snf2 related CREBBP activator protein) mutation (c.7732dupT, p.Ser2578Phefs*6), resulting in early termination of the protein; it was not found in either of his healthy parents or a control population. To our knowledge, this is the first study to describe a boy with Floating-Harbor syndrome with a novel SRCAP mutation diagnosed by targeted exome sequencing in Korea.

Floating-Harbor syndrome (FHS) is a rare human disease characterised by delayed bone mineralisation and growth deficiency, often associated with mental retardation and skeletal and craniofacial abnormalities. FHS was first described at Boston's Floating Hospital 42 years ago, but the causative gene, called Srcap, was identified only recently. Truncated SRCAP protein variants have been implicated in the mechanism of FHS, but the molecular bases underlying the disease must still be elucidated and investigating the molecular defects leading to the onset of FHS remains a challenge. Here we comprehensively review recent work and provide alterative hypotheses to explain how the Srcap truncating mutations lead to the onset of FHS.