Clinical Guidance

Pathogenic variants in exons 33 and 34 of SRCAP that are predicted to cause truncation of the protein (removing three C-terminal AT-hook DNA-binding motifs while leaving the CBP-binding and ATPase domains intact) result in SRCAP-FHS.

Source: GeneReviews — "SRCAP-Related Floating-Harbor Syndrome"

Diagnostic Criteria

No consensus clinical diagnostic criteria for SRCAP-related Floating-Harbor syndrome (SRCAP-FHS) have been published.

Suggestive Findings

SRCAP-FHS should be suspected in individuals with the following clinical and radiographic features. Craniofacial appearance (See .)

• Triangular face

• Deep-set eyes

• Short philtrum

• Wide mouth with thin vermilion of the upper lip

• Long nose with narrow bridge, broad base, broad tip, and low-hanging columella

• Low-set ears

Other features

Source: GeneReviews — "SRCAP-Related Floating-Harbor Syndrome"

Differential Diagnosis

The distinctive facial features, bone age delay, and characteristic speech disability that make the diagnosis of SRCAP-related Floating-Harbor syndrome (SRCAP-FHS) straightforward in early childhood become less distinct with age. lists genes and associated conditions that should be considered in children in whom the diagnosis of SRCAP-FHS is suspected.

Table 3.

Other Genes of Interest in the Differential Diagnosis of SRCAP-Related Floating-Harbor Syndrome

Gene(s) | Disorder | MOI | Clinical Features of Disorder

Overlapping w/SRCAP-FHS | Distinguishing from SRCAP-FHS

CCDC8

CUL7

OBSL1

| Three M syndrome | AR | • Triangular face

• Short 5th fingers

• Bone age may be slightly delayed.

• Males may have hypospadias.

• Severe pre- postnatal growth restriction (final height 5-6 SD below mean; i.e., 120-130 cm)

Source: GeneReviews — "SRCAP-Related Floating-Harbor Syndrome"

Management Guidelines

No clinical practice guidelines for SRCAP-related Floating-Harbor syndrome (SRCAP-FHS) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with SRCAP-FHS, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

SRCAP-Related Floating-Harbor Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Constitutional

| Measurement of growth plotting of growth parameters | Syndrome-specific charts are currently not available for children w/SRCAP-FHS.

Development

| Developmental assessment | • To incl motor, adaptive, cognitive, speech-language eval

• Eval for early intervention/ special education

Neurobehavioral/

Psychiatric

| Neuropsychiatric eval | For persons age 12 mos: screening for concerns incl temper tantrums, ADHD, impulsivity, aggression, OCD, anxiety

Eyes | Ophthalmologic exam to assess for vision deficits strabismus |

Hearing

| Audiologic eval | See Genetic Hearing Loss Overview for details.

Neurology

| • Assessment for clinical manifestations of seizures

• EEG if seizures are suspected

|

Gastroenterology

| • Assessment of feeding

• Assessment for manifestations of gastroesophageal reflux constipation

• Assessment for celiac disease as indicated

|

Kidney/

Source: GeneReviews — "SRCAP-Related Floating-Harbor Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "SRCAP-Related Floating-Harbor Syndrome"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. SRCAP-Related Floating-Harbor Syndrome: Recommended Surveillance

Source: GeneReviews — "SRCAP-Related Floating-Harbor Syndrome"