Bohring-Opitz syndrome

Bohring-Opitz syndrome is a complex developmental condition that affects many body systems, especially growth and neurological development. Pathogenic variants in the ASXL1 gene, which helps regulate how other genes are switched on and off during early development, are a well-established cause. Signs are usually apparent before birth or in the newborn period, so both boys and girls are equally affected from the earliest stages of life. Fewer than one in a million people are thought to have the condition, and only a few dozen individuals have been described in the medical literature. Severity and symptoms vary widely between individuals.

Most babies with Bohring-Opitz syndrome are small for gestational age and continue to have difficulty gaining weight, often requiring special feeding support. Distinctive facial and skull features include a prominent ridge along the forehead (trigonocephaly), a low frontal hairline with thick scalp hair, proptosis or bulging eyes, and a flat reddish birthmark on the forehead. Limbs tend to assume a characteristic posture in which the elbows and wrists are held in flexion, the fingers point toward the little-finger side of the hand, and the hips and feet may also be positioned abnormally. Neurological involvement is significant. Almost all affected children have profound intellectual disability and global neurodevelopmental delay, accompanied by low muscle tone and, in many, seizures. Feeding difficulties, recurrent infections, and visual problems such as severe myopia can complicate care. Less commonly, features such as syndactyly, sacral dimples, or heart and kidney differences are reported. Not all individuals experience every feature, and the degree of cognitive or physical impairment can range from moderate to very severe.

Bohring-Opitz syndrome is most often caused by a single pathogenic variant in the ASXL1 gene. ASXL1 plays an important role in chromatin remodeling, a process that influences when and where other genes are active during early growth. Disruption of this finely tuned system leads to the wide-ranging developmental effects seen in the condition. Most reported individuals have the condition as a result of a new (de novo) change in ASXL1 and therefore have no prior family history. However, both autosomal dominant inheritance from an affected parent and, rarely, autosomal recessive inheritance have been described. When a parent carries an ASXL1 variant, each child has a 50% chance of inheriting it. Families are strongly encouraged to meet with a genetic counselor to discuss individual recurrence risks and family planning options, because expressivity can vary considerably even among relatives who share the same variant.

Currently, management focuses on supportive care and symptom management. Treatment is tailored to the individual and typically involves a multidisciplinary team that may include geneticists, neurologists, developmental pediatricians, dietitians, orthopedists, and physical and occupational therapists. Feeding difficulties often require early involvement of nutrition specialists and, in some cases, placement of a feeding tube to ensure adequate growth. Physical and occupational therapy aim to maintain joint mobility and promote functional skills in daily activities. Seizures are treated with standard anti-seizure medications chosen by a neurologist. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Suggested monitoring includes periodic developmental assessments, vision checks for myopia, evaluation of muscle tone and joint contractures, and tracking of growth parameters. Families should discuss individualized surveillance schedules with their care team. Because no targeted or curative therapies exist yet, participation in research studies may provide access to investigational approaches. Genetic counseling should be offered to all families for guidance on inheritance, testing of relatives, and future pregnancies.

Outcomes depend on many factors including the severity of feeding issues, the presence of seizures, and access to specialized care. Some children achieve limited developmental milestones, while others remain dependent on caregivers for all activities of daily living. Although medical complications can be serious, supportive interventions have improved comfort and lengthened survival for many affected individuals. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert centers and patient advocacy groups for up-to-date guidance and community support, and genetic counseling can provide additional resources for long-term planning.

Clinical trials are underway exploring new treatment approaches for Bohring-Opitz syndrome and related developmental disorders. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.