Rubinstein-Taybi Syndrome

Excerpt

Clinical characteristics: Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive facial features, broad and often angulated thumbs and halluces, short stature, and moderate-to-severe intellectual disability. Characteristic craniofacial features include downslanted palpebral fissures, low-hanging columella, high palate, grimacing smile, and talon cusps. Prenatal growth is often normal, then height, weight, and head circumference percentiles rapidly drop in the first few months of life. Short stature is typical in adulthood. Obesity may develop in childhood or adolescence. Average IQ ranges between 35 and 50; however, developmental outcome varies considerably. Some individuals with EP300-related RSTS have normal intellect. Additional features include ocular abnormalities, hearing loss, respiratory difficulties, congenital heart defects, renal abnormalities, cryptorchidism, feeding problems, recurrent infections, and severe constipation.

Diagnosis/testing: The diagnosis of RSTS is established in a proband with characteristic clinical features. A heterozygous pathogenic variant in CREBBP or EP300 identified by molecular genetic testing confirms the diagnosis if clinical features are inconclusive.

Management: Treatment of manifestations: Early intervention programs, special education, vocational training to address developmental disabilities, referral to behavioral specialists / psychologists, and support groups / resources for family members; standard treatment for eye abnormalities, hearing loss, sleep apnea, cardiac anomalies, renal anomalies, cryptorchidism, and dental anomalies; aggressive management of gastroesophageal reflux and constipation; surgical repair of significantly angulated thumbs or duplicated halluces.

Surveillance: Monitoring of growth and feeding, especially in the first year of life; annual eye and hearing evaluations; routine monitoring for cardiac, renal, and dental anomalies.

Pregnancy management: Preeclampsia or placental abnormalities have been reported in some pregnancies with RSTS.

Genetic counseling: RSTS is inherited in an autosomal dominant manner. Most individuals diagnosed with RSTS have the disorder as the result of a de novo pathogenic variant and are the only affected member of their families. Rarely, an individual diagnosed with RSTS has the disorder as the result of a CREBBP or EP300 pathogenic variant inherited from a heterozygous or mosaic parent. Each child of an individual with RSTS has a 50% chance of inheriting the RSTS-related pathogenic variant. Once the RSTS-related pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing for RSTS are possible.