Bohring-Opitz Syndrome: Mutation in the ASXL1 Gene as a Rare Cause of Mental Retardation with Failure to Thrive and Characteristic Phenotype

Case Study: We report a 6-month-old baby with a suspected diagnosis of Bohring-Opitz syndrome. Bohring-Opitz syndrome is a malformation syndrome with variable clinical peculiarity. It is mainly characterized by 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 (Bohring 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 joint.

Causative für the disease are mainly de novo heterozygous nonsense or truncating mutations in the ASXL1 gene. Not all of the affected children carry mutations, suggesting genetic heterogeneity. The ASXL1 gene is involved in the maintenance of both activation and silencing of the HOX genes, which are involved in body patterning, as well as in chromatin remodeling. The cause for the failure to thrive is yet not known.

In the reported case the child presented in our neuropediatric department for further diagnostic work up of a global developmental delay in combination with failure to thrive. Besides the aforementioned features, that were particularly mildly developed, we found an unspecific delay in myelination in MRI scan of the brain in combination with a hypoplastic corpus callosum and subependymal heterotopia, all according to the reported literature. A diagnostic work up of the failure to thrive revealed no specific causes except for a hyperechogenic pancreas. To date, we therapeutically try a balanced diet in combination with substitution of pancreas enzymes.

Conclusion: The clinical combination of characteristic BOS posture of the upper extremity at birth, failure to thrive, global developmental delay with characteristic dysmorphic features should give reason to a molecular genetic exclusion of Bohring-Opitz syndrome.

Keywords: Bohring-Opitz syndrome, malformation syndrome, subependymal heterotopia.