SRCAP- Related Floating-Harbor Syndrome

Excerpt

Clinical characteristics: SRCAP-related Floating-Harbor syndrome (SRCAP-FHS) is characterized by typical craniofacial features; low birth weight, normal head circumference, and short stature; bone age delay that normalizes between ages six and 12 years; skeletal anomalies (brachydactyly, broad fingertips, clinodactyly, short thumbs, prominent joints, and clavicular abnormalities); severe receptive and expressive language impairment; hypernasality and high-pitched voice; and intellectual disability that is typically mild to moderate. Difficulties with temperament and behavior, present in many children, tend to improve in adulthood. Other features can include hyperopia and/or strabismus, conductive hearing loss, seizures, gastroesophageal reflux, renal anomalies (e.g., hydronephrosis / renal pelviectasis, cysts, and/or agenesis), and genital anomalies (e.g., hypospadias and/or undescended testes).

Diagnosis/testing: The diagnosis is established in a proband with suggestive findings and a heterozygous SRCAP pathogenic variant identified by molecular genetic testing.

Management: Treatment of manifestations: Referral to an endocrinologist for consideration of human growth hormone (HGH) therapy; however, data on use of HGH in SRCAP-FHS are limited. Early intervention programs, special education, and vocational training to address developmental disabilities; communication rehabilitation with sign language or alternative means of communication; behavior management by a behavioral specialist / psychologist with consideration of medication as needed. Standard treatment for refractive errors, strabismus, hearing loss, seizures, gastroesophageal reflux, constipation, kidney and genitourinary anomalies, orthopedic, dental, and cardiac issues; family and social work support.

Surveillance: Close monitoring of growth, especially in the first year of life. Bone age and evaluation for signs of early puberty as needed, especially in those on HGH. Monitor developmental progress and educational needs at each visit. Assess for seizures, gastroesophageal reflux, constipation, and manifestations of celiac disease at each visit. Annual behavioral assessment, ophthalmologic evaluation, audiology evaluation, blood pressure measurement, and assessment of kidney function. Monitor kidney anomalies per nephrologist. Kidney ultrasound to assess for cysts in teenage and adult years with follow up as needed. Orthopedic assessment for kyphoscoliosis and clinical manifestations of Perthes disease as needed. Dental evaluation every six months.

Genetic counseling: SRCAP-FHS is inherited in an autosomal dominant manner. The majority of affected individuals have a de novo pathogenic variant. Each child of an individual with SRCAP-FHS has a 50% chance of inheriting the pathogenic variant. Prenatal and preimplantation genetic testing are possible for families in which the pathogenic variant has been identified.