blepharophimosis - intellectual disability syndrome, SBBYS type

Blepharophimosis-intellectual disability syndrome, SBBYS type is a very rare multisystem developmental disorder that combines distinctive facial features, congenital hypothyroidism, extra fingers or toes, and significant neurodevelopmental challenges. It is caused by pathogenic variants in the KAT6B gene, which encodes a protein important for turning other genes on and off during early growth. Signs are usually apparent at birth or in early infancy and affect both males and females. Fewer than one in a million people worldwide are thought to have this condition, with fewer than 20 individuals reported in medical literature.

The clinical picture is broad and can differ from child to child. Characteristic facial findings include small eyelid openings (blepharophimosis), a bulbous nose, thin upper lip, low-set ears, micrognathia, and often a small head size. Many newborns present with congenital hypothyroidism, which may lead to prolonged jaundice, poor feeding, and slowed growth if untreated. Severe intellectual disability is consistently reported, and most children require lifelong support for cognitive and developmental needs. Neurological features such as hypotonia can make head control and early motor milestones challenging, while feeding difficulties are common in infancy. Several body systems may be involved. Musculoskeletal differences include postaxial polydactyly, long thumbs or big toes, and generalized joint laxity. Growth delay may persist even with thyroid hormone replacement. In males, cryptorchidism and hypospadias are frequent, and some individuals have hearing impairment or a cleft palate that can impact speech and feeding. Cardiac anomalies, most often a ventricular septal defect, have been described in a subset of patients. Not all individuals experience all features, and severity varies considerably. Ongoing developmental, endocrine, and orthopedic evaluations help clarify each person’s unique strengths and challenges.

Blepharophimosis-intellectual disability syndrome, SBBYS type results from pathogenic variants in the KAT6B gene. The KAT6B protein is a histone acetyltransferase that helps regulate the activity of many other genes during embryonic development; disrupting this regulation can lead to the broad range of features seen in the disorder. The condition is inherited in an autosomal dominant pattern, meaning one altered copy of KAT6B is sufficient to cause the syndrome. When an affected individual has children, each pregnancy carries a 50 percent chance of passing on the variant. Even within the same family, the specific symptoms and their severity can vary markedly (variable expressivity), so genetic counseling is strongly recommended for relatives considering family planning.

Currently, management focuses on supportive care and symptom management tailored to each individual. Congenital hypothyroidism is treated with lifelong thyroid hormone replacement, monitored regularly by an endocrinologist. Early intervention services, including physical, occupational, and speech therapy, address hypotonia and developmental delays, while feeding specialists can help infants with poor oral intake. Surgical repair may be required for cleft palate, cryptorchidism, or significant cardiac defects. Because the syndrome affects multiple organ systems, ongoing surveillance is an essential part of long-term care. A multidisciplinary team typically includes endocrinology, cardiology, orthopedics, developmental pediatrics, audiology, and genetic counseling, with regular monitoring to detect complications early and adjust interventions as needed. Families should work closely with their healthcare team to develop an individualized care plan and reevaluate needs over time.

Long-term outcomes depend on the severity of endocrine, developmental, and medical issues in each person. Early recognition and treatment of hypothyroidism, timely surgical interventions, and comprehensive developmental support can improve overall health and quality of life. Severe intellectual disability remains common, so most individuals will need lifelong assistance with daily activities. Severity and symptoms vary widely between individuals, and predicting future abilities for a newborn is difficult. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert centers and genetic counselors for up-to-date guidance and support.