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. Drawbacks to findings
From the same group, three individuals whose phenotype most closely resembled FHS carried no mutation on the SRCAP gene.
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 FHSSpecial 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. History
The first identified instances occurred in 1973 at the Boston Floating Hospital, and in 1975 at Harbor General Hospital in Torrance, California. The name Floating–Harbor syndrome was coined by Robinson et al. in 1988. Since then approximately 40 more cases have been described.The first case recorded was that of a 5-year-old boy. In a 32-year follow up done in 2006, the patient was in good overall health, had never been hospitalized, and had been employed for the past 15 years. His mother stated he had a very good memory, was gregarious, had a temper, and at times was stubborn.