Bohring–Opitz syndrome

Overview

Bohring–Opitz syndrome (BOS) is a rare and severe genetic disorder characterized by distinctive facial features, profound developmental delay, feeding difficulties, and abnormal posture known as the “BOS posture” — flexion of the elbows and wrists with ulnar deviation. The condition was first described in the 1990s and is often diagnosed in infancy. Children with Bohring–Opitz syndrome have complex medical needs and are at increased risk for complications such as respiratory issues, seizures, and feeding problems. Despite its rarity, increased awareness and genetic testing have improved early diagnosis and supportive care.

Causes

Bohring–Opitz syndrome is caused by mutations in the ASXL1 gene (Additional Sex Combs Like 1), which plays an important role in chromatin remodeling and gene expression regulation. Most cases occur due to de novo mutations, meaning they arise spontaneously and are not inherited from a parent. In rare instances, parental mosaicism (where the mutation is present in some of the parent’s cells) may be involved. The condition follows an autosomal dominant inheritance pattern, though familial transmission is exceedingly rare due to the high mortality rate and reduced reproductive fitness of affected individuals.

Symptoms

Bohring–Opitz syndrome presents with a wide range of physical and neurological abnormalities. Common features include:

• Distinctive facial features:

  • Prominent eyes

  • Trigonocephaly (triangular-shaped forehead)

  • Low-set ears

  • Flat nasal bridge

  • Micrognathia (small jaw)

• BOS posture – flexion and deviation of elbows and wrists with clenched fists

• Severe global developmental delay

• Hypotonia or hypertonia (low or high muscle tone)

• Feeding difficulties and failure to thrive

• Respiratory issues – including apnea or chronic lung disease

• Seizures – often difficult to control

• Vision and hearing impairments

• Microcephaly – smaller than average head size

• Increased risk of Wilms tumor – a type of kidney cancer, though rare

Diagnosis

Diagnosis of Bohring–Opitz syndrome is based on clinical evaluation and confirmed by genetic testing. Diagnostic steps include:

• Physical examination – identifying characteristic facial features and BOS posture

• Developmental assessment – to evaluate motor, cognitive, and speech delays

• Genetic testing – through whole exome sequencing or targeted testing to identify mutations in the ASXL1 gene

• Imaging studies – such as brain MRI to evaluate for structural abnormalities

• Abdominal ultrasound – for screening of Wilms tumor during early childhood

Treatment

There is no cure for Bohring–Opitz syndrome, so treatment is supportive and tailored to the individual’s needs. Management typically involves a multidisciplinary team. Key components include:

• Feeding support:

  • Nasogastric or gastrostomy tube placement for nutrition

  • Feeding therapy and dietary management

• Seizure management:

  • Antiepileptic medications and neurologist follow-up

• Respiratory care:

  • Monitoring and treatment of breathing issues or sleep apnea

• Developmental therapy:

  • Physical, occupational, and speech therapy to improve function and mobility

• Regular tumor screening:

  • Ultrasound to monitor for Wilms tumor in early childhood

• Vision and hearing interventions – including assistive devices

Prognosis

The prognosis for individuals with Bohring–Opitz syndrome is generally poor, particularly in infancy and early childhood. Many affected infants have severe medical complications and reduced life expectancy. However, some children survive into adolescence or adulthood with intensive medical support and therapy. Quality of life depends on the severity of symptoms and the ability to manage complications such as seizures and feeding issues. Early diagnosis and comprehensive care can improve outcomes and provide support for families coping with this complex disorder.