Floating–Harbor syndrome and polycystic kidneys associated with SRCAP mutation

Abstract

Floating-Harbor syndrome (FHS) is a rare genetic disorder recently shown to be caused by mutations in the Snf2-related CREB-binding protein activator protein gene (SRCAP). It comprises three key clinical features of characteristic facies, expressive and receptive speech impairment and short stature. We report on a patient with this syndrome associated with early adult-onset hypertension and bilateral polycystic kidneys. Family screening for polycystic kidney disease was negative and mutations in polycystic kidney disease 1 and 2 genes (PKD1 and PKD2) were absent. Sequencing of the SRCAP gene demonstrated a de novo mutation matching one of the known FHS-associated mutations. The patient required treatment with anti-hypertensives and will require lifelong renal monitoring. We suggest this patient's presentation may be due to the pleiotropic effects of SRCAP mutations. Further, the protein encoded by SRCAP is known to interact with CREB-binding protein, the product of the gene mutated in Rubinstein-Taybi syndrome, which is associated with renal abnormalities. A literature review of the renal findings in patients with Floating-Harbor syndrome identified another patient with possible polycystic kidneys, two patients with early onset hypertension, and a young patient with a ruptured intracranial aneurysm, which can be a feature of classic adult polycystic kidney disease. Collectively, these findings suggest that all patients with Floating-Harbor syndrome should undergo regular blood pressure monitoring and screening for polycystic kidneys by ultrasound at the time of the FHS diagnosis with imaging to be repeated during adulthood if a childhood ultrasound was negative.

The phenotype of Floating-Harbor syndrome: clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

“…The average age of diagnosis was 8 years. Two mother/daughter pairs [7,8] and a number of the other subjects have been previously reported in the literature [1,3,6,7,9-11]. All the mutations identified in our cohort were truncating (nonsense or frameshift) alleles (Table 1).…”

Expanded spectrum of exon 33 and 34 mutations in SRCAP and follow-up in patients with Floating-Harbor syndrome

“…Institut für Vegetative Anatomie, Charité -Universitätsmedizin Berlin, Berlin, Germany. 2 Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. 3 Institut für Medizinische Genetik, Universität Rostock, Rostock, Germany.…”

“…Recently mutations located in exon 34 of the Snf2-related CREBBP activator protein (SRCAP) gene, encoding the core catalytic component of the multiprotein chromatinremodeling SRCAP complex, were found to cause FHS in about 50 patients [1][2][3][4]. One patient who carried an exon 33 SRCAP mutation has been reported [5].…”

Floating Harbor Syndrome

“…Some developmental delay, especially in speech is common though great variability in intellect is reported. Additional features described in different reports include gluten intolerance, conductive hearing loss and polycystic kidney disease [3,4]. Most of the mutations described are truncating and appear to be clustered in the last (34th) exon as seen in this case also [2].…”