Say-Barber-Miller syndrome

Say-Barber-Miller syndrome (also known as Say-Barber-Biesecker-Young-Simpson syndrome or Ohdo syndrome, SBBYS variant) is an extremely rare genetic disorder characterized by a distinctive combination of congenital anomalies. The condition was initially described by Say, Barber, and Miller and is now known to be caused by mutations in the KAT6B gene (also known as MYST4), which encodes a histone acetyltransferase involved in chromatin remodeling and gene regulation. The syndrome primarily affects multiple body systems including the craniofacial structures, musculoskeletal system, and central nervous system. Key clinical features include a mask-like, immobile facial appearance (blepharophimosis, long philtrum, and a small mouth), severe intellectual disability, and significant developmental delay. Affected individuals typically present with joint stiffness or contractures, genital anomalies (particularly cryptorchidism in males), dental anomalies, and thyroid dysfunction (hypothyroidism). Congenital heart defects may also be present. Additional features can include hearing loss, patellar hypoplasia or aplasia, and lacrimal duct anomalies. The facial features, which include narrow palpebral fissures and a flat nasal bridge, are often recognizable in infancy. There is currently no cure for Say-Barber-Miller syndrome, and management is supportive and symptomatic. Treatment typically involves a multidisciplinary approach including early intervention programs for developmental delay, thyroid hormone replacement for hypothyroidism, surgical correction of cardiac or genital anomalies when indicated, and orthopedic management for joint contractures. Regular monitoring of thyroid function, hearing, and cardiac status is recommended. Speech therapy, physical therapy, and occupational therapy are important components of ongoing care.

Common questions about Say-Barber-Miller syndrome