Intracranial vascular pathology in two further patients with Floating-Harbor syndrome: Proposals for cerebrovascular disease risk management

Eur J Med Genet. 2020 Apr;63(4):103785. doi: 10.1016/j.ejmg.2019.103785. Epub 2019 Oct 9.


Floating-Harbor syndrome (FHS) is a rare, heritable disorder caused by variants in the SRCAP gene. Most individuals with FHS have characteristic facial features, short stature, and speech and language impairment. Although FHS has been likely under-diagnosed due to a combination of lack of recognition of the clinical phenotype and limited access to genomic testing, it is a rare condition with around 100 individuals reported in the medical literature. Case series have been biased towards younger individuals (vast majority <20 years of age) meaning that it has been challenging to provide accurate medical advice for affected individuals in adulthood. We report two young adults with FHS who presented with intracranial haemorrhage likely secondary to cerebrovascular aneurysms, with devastating consequences, making a total of four FHS patients reported with significant cerebrovascular abnormalities. Three of four patients had hypertension, at least one in conjunction with normal renal structure. We consider possible relationships between hypertension, renal pathology and aneurysms in the context of FHS, and consider mechanisms through which disruption of the SRCAP protein may lead to vascular pathology. We recommend that clinicians should have a low threshold to investigate symptoms suggestive of cerebrovascular disease in FHS. We advise that patients with FHS should have annual blood pressure monitoring from adolescence, renal ultrasound at diagnosis repeated in adulthood, and timely investigation of any neurological symptoms. For patients with FHS, particularly with hypertension, we advise that clinicians should consider at least one MRA (Magnetic Resonance Imaging with Angiography) to check for cerebral aneurysms.

Keywords: Cerebral aneurysm; Cerebrovascular disease; Floating-harbor syndrome; Hypertension; Neuroradiological screening; Subarachnoid haemorrhage.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple
  • Adenosine Triphosphatases / genetics*
  • Adenosine Triphosphatases / metabolism
  • Adult
  • Cerebrovascular Disorders / etiology
  • Cerebrovascular Disorders / pathology*
  • Cerebrovascular Disorders / therapy
  • Craniofacial Abnormalities / complications*
  • Female
  • Growth Disorders / complications*
  • Heart Septal Defects, Ventricular / complications*
  • Humans
  • Male
  • Mutation*
  • Phenotype
  • Prognosis
  • Risk Management / methods*


  • Adenosine Triphosphatases
  • SRCAP protein, human

Supplementary concepts

  • Floating-harbor syndrome