SNP Shot: Genomic Insights

Bohring-Opitz syndrome (BOS) is a rare genetic disorder impacting the development of multiple body systems.

Individuals with BOS typically experience significant intellectual disability, delayed development, and seizures. While most have a normal head shape and size without brain abnormalities, some exhibit atypical head development, potentially leading to a smaller than normal head (microcephaly) or trigonocephaly, characterized by a pointed forehead. Structural brain anomalies, such as enlarged ventricles (ventriculomegaly) or a thin corpus callosum (the tissue connecting the brain's hemispheres), may occur independently of head abnormalities.

Vision problems are common in BOS. These can include protruding eyes (exophthalmos), misaligned eyes (strabismus), widely spaced eyes (hypertelorism), and upward-slanting outer corners of the eyes (upslanting palpebral fissures). Individuals may also have severe nearsightedness (high myopia) or abnormalities affecting the retina or the optic nerves.

Distinctive facial features associated with BOS may include a flattened nasal bridge, nostrils that point forward (anteverted nares), a highly arched palate or a cleft palate, a cleft lip, a small lower jaw (micrognathia), low-set, backward-rotated ears, a red birthmark (nevus simplex) on the face (often the forehead), a low frontal hairline with eyebrows that meet in the middle (synophrys), and excessive body and facial hair (hirsutism) that becomes more pronounced with age.

Some individuals with BOS experience poor growth before birth (intrauterine growth restriction). After birth, they may exhibit slow growth and weight gain, often accompanied by severe feeding difficulties and recurrent vomiting.

A characteristic body posture, referred to as Bohring-Opitz syndrome posture, is often observed. This involves slouched shoulders, bent elbows and wrists, and hands with ulnar deviation (where the wrists or fingers angle outward toward the little finger), along with straight legs. This posture often diminishes as individuals age. Other common features include joint contractures (fixed bending of joints) present at birth, and abnormal muscle tone. Recurrent infections, heart, kidney, or genital abnormalities may also occur. Rarely, a childhood kidney cancer called Wilms tumor can develop.

The lifespan of individuals with BOS varies. Some may not survive past early childhood, while others live into adolescence or young adulthood. Common causes of death include heart problems, airway abnormalities causing pauses in breathing (obstructive apnea), and lung infections.

Inheritance:

Bohring-Opitz syndrome is typically considered an autosomal dominant disorder, meaning that a single copy of the mutated gene in each cell is sufficient to cause the condition. Most cases arise from new (de novo) mutations in the responsible gene during the formation of egg or sperm cells or in early embryonic development. These cases occur in families with no prior history of BOS. To date, there are no known instances of individuals with Bohring-Opitz syndrome having children. In rare instances, an individual with BOS may inherit the altered gene from a parent with mosaicism, where the mutation is present only in some of their cells, including egg cells, but not others.