The cause of this condition is unknown but evidence of familial inheritance and sporadic genetic mutation has been linked to cases of FHS. Two possibly familial cases have been reported—one in a mother and son, and the other in a mother and daughter. This suggests an autosomal dominant inheritance but additional cases need to be investigated to establish this. Another report has suggested that the inheritance may be autosomal recessive. In all of these cases, however, the mothers and children were not similarly affected, suggesting a variable clinical expression of the syndrome.

In a study published by the "American Journal of Human Genetics" in 2012, exome sequencing was used to investigate a group of unrelated individuals with classic features of FHS and identified heterozygous mutations in SRCAP as causative of this disorder. Each reported mutation was truncating (nonsense or frameshift) and occurred between codons 2,407 and 2,517 in exon 34, resulting in the loss of three C-terminal AT-hook motifs. SRCAP encodes a SNF2-related chromatin-remodeling ATPase that is a coactivator for CREB-binding protein (or CBP), which is the major cause of Rubinstein–Taybi syndrome. This disrupted interaction between the proteins most likely explains the clinical overlap between FHS and RTS.

- SRCAP has been shown to transduce signals of nuclear (steroid) hormone receptors and Notch pathways, showing that it plays diverse roles in gene expression.

- SRCAP contains several functional domains (SNF2 like ATPase, an N-terminal HSA domain, and three C-terminal AT-hook DNA-binding motifs).

- The CBP interaction domain of SRCAP is located centrally.

Thus, the mechanism of disease in FHS is suspected to be dominant-negative (or antimorphic) due to the mutation in the final exon that results in the loss of the major transactivation function of SRCAP (or loss of one or more critical domains). All of the patients that carried the mutation also had obvious physical symptoms (i.e., prominent nose, delayed bone age, and short stature). Those who tested negative for the mutation often had dysmorphic facial features distinct from classical FHS, as well as a formal diagnosis of autism.

There are no cures for FHS. Close monitoring of growth in the first few years is essential, as well as annual general health screening and tests listed below. An FHS diagnosis will affect the individual and those there to support them.

Managing symptoms and features of FHS involves maintaining a close watch on the patient's physical as well as mental health. This would include:

- Sequencing of SRCAP exons 31–34 in all suspected cases

- Complete assessments of auditory and visual systems

- Renal and urinary tract ultrasound

- Orthopedic assessment of hip dysplasia and clavicle abnormalities

- Neurologic assessment if there is a suspicion of seizures

- Dental hygiene to prevent cavities and to monitor for malocclusion

- Evaluation for growth hormone deficiency at baseline, to be repeated if loss of growth velocity occurs

- Monitoring of bone age and pubertal timing in case of precocious puberty

- Psychoeducational assessments corrected for deficiencies in expressive language and sensory issues

- Monitoring of behavioral disturbances and provision of early intervention

- Counseling for families regarding recurrence risk and the offspring of individuals with FHS

Special education programs and vocational training to address developmental disabilities are highly recommended, as well as communication rehabilitation with sign language or alternative means of communication. Behavior management strategies could also include referrals to behavior specialists or psychologists for help. For those concerned, genetic counseling can be sought for issues related to testing of at-risk relatives.

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.

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