Patients with Floating Harbor syndrome [OMIM #136140] typically have short stature, delayed osseous maturation and expressive-language deficits. Distinctive facial features of affected individuals include a triangular shaped face, short philtrum, wide mouth, and a long nose with a broad base, full tip and low hanging columella. The majority of affected individuals have some degree of intellectual impairment or learning disability, ranging from moderate intellectual disability to borderline normal intelligence. Other associated features include skeletal anomalies, genitourinary anomalies, celiac disease, congenital heart defects, and a high-pitched or nasal voice. Floating Harbor syndrome shares many key clinical features with Rubinstein-Taybi syndrome [OMIM #180849], including short stature, a long nose with low hanging columella, and anomalous thumbs.
Hood et al. (2012) identified mutations in the SRCAP gene (SNF2-related CBP activator protein) [OMIM #611421] in 13/13 (100%) patients with Floating Harbor syndrome. Goff et al. (2012) identified SRCAP mutations in 6/9 affected individuals (67%). SRCAP has 34 coding exons and is located at 16p11.2. It encodes a switch/sucrose nonfermentable-type chromatin-remodeling ATPase, which is a potent coactivator for CREB-binding protein (CREBBP, the major cause of Rubenstein-Taybi syndrome) and CBP-mediated transcription. All mutations reported to date are truncating mutations that occur in exon 34.