title: 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.
authors.affiliation: Oxford Kidney Unit, Churchill Hospital, Oxford, UK. michael.reschen@stx.ox.ac.uk
authors.forename: Michael
authors.initials: M
authors.lastname: Reschen
authors.forename: Usha
authors.initials: U
authors.lastname: Kini
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hood
authors.forename: Kym M
authors.initials: KM
authors.lastname: Boycott
authors.forename: Jane
authors.initials: J
authors.lastname: Hurst
authors.forename: Christopher A
authors.initials: CA
authors.lastname: O'Callaghan
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D019465:Craniofacial Abnormalities / Q000235:genetics*; D006130:Growth Disorders / Q000235:genetics*; D006345:Heart Septal Defects, Ventricular / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D007690:Polycystic Kidney Diseases / Q000235:genetics*
chemical_list: D000251:Adenosine Triphosphatases; C119652:SRCAP protein, human