Bohring-Opitz syndrome (BOS).
Incidence
Bohring-Opitz syndrome is caused by mutations in the ASXL1 gene. There are no reports of BOS mutations being passed down from parent to child. All reports of BOS indicate that neither parent carries the same mutation and the mutation was new in the child (de novo). More than 40 affected individuals have been described in the scientific literature.
Clinical Characteristics
Bohring-Opitz syndrome is a malformation syndrome characterized by severe intrauterine growth retardation, poor feeding, profound mental retardation, trigonocephaly, prominent metopic suture, exophthalmos, nevus flammeus of the face, upslanting palpebral fissures, hirsutism, and flexion of the elbows and wrists with deviation of the wrists and metacarpophalangeal joints. Bohring-Opitz syndrome (BOS) is a rare, multiple anomaly syndrome that most often is evident at birth (congenital) and affects an individual’s growth, development, and variable organ-systems. Individuals with BOS often have severe growth restriction and are therefore quite small; they may have feeding difficulties, characteristic facial features, and the presence of a red or pink birthmark (nevus flammeus) on the forehead or eyelids. Individuals may also have seizures, heart anomalies, and a characteristic ‘BOS posture’ where the elbows are bent and wrists angle outwards. Additional abnormalities may include a smaller than average head size (microcephaly), a visible ridge over the forehead (metopic ridge), a cleft lip and/or palate, eye abnormalities, recurrent infections, and pauses during breathing while asleep (sleep apnea), as well as sleep difficulties. Children with BOS may have varying degrees of learning differences, but these are generally severe, and most children do not attain typical speech or ambulation. Bohring-Opitz syndrome is caused by mutations in the ASXL1 gene. There are currently no known medications or disease-specific therapies, but supportive treatment involving physical/occupational/speech therapy and specific management of an individual’s symptoms are considered the standard of care. BOS can theoretically be transmitted in an autosomal dominant manner (where 50% of an individual’s children are at risk of inheriting the gene), but most individuals do not reproduce due to developmental and neurologic impairments. There are no reports of BOS mutations being passed down from parent to child. All reports of BOS indicate that neither parent carries the same mutation and the mutation was new in the child (de novo).
Precipitants
None
Provocation Tests
None.
Diagnostic Procedures
The definitive diagnosis of BOS is made after molecular testing for mutations in the ASXL1 gene. The observation of a common phenotype in Bohring-Opitz syndrome has led to the development of diagnostic criteria, including microcephaly, trigonocephaly, palatal abnormalities, prominent eyes and hypoplastic supraorbital ridges, upslanting palpebral fissures, depressed nasal bridge and anteverted nares, facial nevus flammeus, low-set, posteriorly angulated ears, failure to thrive, and severe developmental delay. In addition, patients have an unusual and characteristic limb posture, with external rotation and/or adduction of shoulders, flexion at elbows and wrists, and ulnar deviation of wrists and/or fingers at the metacarpophalangeal (MCP) joint. Clinical suspicion for BOS may be raised if an individual displays the characteristic BOS posturing of the hands and elbows, is having delayed growth and developmental milestones, and has the characteristic facial features seen in BOS, including the presence of characteristic birthmarks.