Bohring-Opitz Syndrome (BOS) is a rare genetic disorder typically noticeable at birth, impacting an individual’s growth, development, and various organ systems. It is characterized by severe developmental delays, intellectual disability, and distinctive facial features. This condition presents significant challenges for affected individuals and their families.
Genetic Basis
Bohring-Opitz Syndrome primarily arises from mutations in the ASXL1 gene. This gene provides instructions for a protein involved in chromatin remodeling, influencing how DNA is packaged and genes are expressed, which is crucial for early development.
In most instances, the mutation in the ASXL1 gene is sporadic, occurring spontaneously and not inherited from either parent (a “de novo” mutation). While typically not inherited, there are rare instances of parental mosaicism, where a parent carries the mutation in some cells but does not display symptoms, which could lead to recurrence in future children.
Recognizing the Signs
Individuals with Bohring-Opitz Syndrome present with a range of distinctive clinical features and physical characteristics.
Facial Features
Prominent forehead
Widely spaced eyes (hypertelorism)
Red birthmark on the forehead (glabellar nevus flammeus), which tends to fade with age
Full cheeks
Small nose with anteverted nares
Small lower jaw (micrognathia)
Cleft lip or palate
Synophrys (eyebrows growing together)
Excessive body hair (hirsutism)
Feeding difficulties are common and often severe in infancy, including issues like cyclic vomiting and poor weight gain, sometimes necessitating tube feeding. These feeding challenges can significantly impact overall health, though they may improve with age. Severe intellectual disability and global developmental delays are consistently observed, affecting motor skills, cognitive development, and speech acquisition. Many individuals do not develop independent walking or typical speech.
A characteristic posture, known as “BOS posture,” is often seen, involving flexion at the elbows with ulnar deviation of the wrists and flexion of the metacarpophalangeal joints. This posture is most pronounced in early childhood and may become less apparent over time. Other limb abnormalities can include joint contractures present at birth.
Seizures are frequent among individuals with Bohring-Opitz Syndrome and are generally responsive to standard medications. Recurrent infections, particularly respiratory, ear, and urinary infections, are also common, especially in infancy, and can be more severe and prolonged than in unaffected children. Cardiac anomalies, such as transient bradycardia and septal defects, along with structural brain anomalies like corpus callosum defects and enlarged ventricles, may also be present. There is also a reported increased risk for certain pediatric cancers, such as Wilms tumor.
Confirming the Diagnosis
Diagnosing Bohring-Opitz Syndrome typically involves a two-pronged approach, combining clinical observation with genetic confirmation. Healthcare providers first assess for the constellation of characteristic physical features and developmental patterns.
Following clinical suspicion, genetic testing is essential to confirm the diagnosis. This usually involves molecular genetic testing, such as whole exome sequencing or targeted gene sequencing specifically looking for pathogenic variants in the ASXL1 gene. Genetic confirmation is important for a definitive diagnosis, as some features can overlap with other genetic conditions.
Comprehensive Care
Managing Bohring-Opitz Syndrome involves a comprehensive, multidisciplinary approach focused on addressing individual symptoms and providing supportive care. Medical teams often include neurologists, gastroenterologists, pulmonologists, and other specialists to manage the diverse health issues. For feeding difficulties, nutritional support and feeding therapies are often necessary, which may include the use of gastrostomy tubes for adequate nutrition.
Respiratory problems, common in affected individuals, may require interventions ranging from medication to, in severe cases, a tracheostomy to support breathing. Seizures are managed with anticonvulsant medications. Developmental delays are addressed through various therapeutic interventions, including physical therapy to improve mobility and muscle strength, occupational therapy to enhance daily living skills, and speech therapy for communication development. Early intervention programs are often recommended to support learning and development from infancy.
Understanding the Outlook
The outlook for individuals with Bohring-Opitz Syndrome presents significant challenges due to the severe neurological impairment and complex medical issues. Life expectancy can be reduced, with a number of children not surviving past early childhood, often due to complications like severe infections or respiratory and cardiac problems.
Despite these challenges, advancements in supportive medical care have improved the quality of life and, for some, extended survival beyond infancy. Individuals who survive infancy may experience some improvement in issues like feeding difficulties and recurrent infections. Outcomes can vary, with some individuals living into adolescence or early adulthood, though independent living is typically not achieved due to ongoing care needs. Ongoing medical follow-ups and tailored therapies are important for managing symptoms and enhancing well-being over time.