Until recently, doctors have diagnosed patients with FHS based on clinical observations and how well they fit the disease description, usually occurring in early childhood. Molecular genetic testing is also used now to test for genetic mutations. By performing a sequence analysis test of select exons, mutations can be detected in exon 34 of the SRCAP gene. This mutation has been observed in 19 patients to date.

In most cases, if the patient shows classic facial features of FHS, the molecular testing will show a mutation on the SRCAP gene.

FHS shares some common features with Rubinstein–Taybi (due to overlapping effects of mutations on SRCAP), however cranial and hand anomalies are distinctive: broad thumbs, narrow palate, and microcephaly are absent in Floating-Harbor Syndrome. One child in the UK has a diagnosis of microcephaly alongside Floating–Harbor syndrome.

Treatment includes anti-anxiety medication, anti-depressants such as SSRIs, or sedatives.

The cause of feline hyperesthesia syndrome is unknown. Some experts believe FHS to be a form of epilepsy, while others believe it is a behavioural disorder triggered by trauma. Noting that affected cats tend to be dominating rather than submissive, some research argues that FHS is conflict displacement in which the cat acts out thwarted territorial disputes on its own body.

Although any age, breed, or sex of cat can develop feline hyperesthesia syndrome, those most susceptible include the Siamese, Burmese, and Himalayan breeds.