SNP Shot: Genomic Insights

Frontonasal dysplasia is a developmental disorder that arises during prenatal development, affecting the head and face. Individuals with this condition exhibit at least two of the following characteristics: widely set eyes (ocular hypertelorism), a broad nose, a nasal cleft (a split in one or both sides of the nose), absence of the nasal tip, a midline cleft involving the nose, upper lip, or palate, incomplete formation of the frontal skull with skin covering where bone should be (anterior cranium bifidum occultum), or a widow's peak.

Additional features that may be present in individuals with frontonasal dysplasia include other facial abnormalities, absence or malformation of the corpus callosum (the tissue connecting the brain's hemispheres), and intellectual disability.

Frontonasal dysplasia is classified into at least three types, each distinguished by its genetic cause and associated symptoms. Besides the previously mentioned features, each type is linked to specific characteristics. Type 1 is often characterized by nasal abnormalities, a long philtrum (the area between the nose and upper lip), and drooping eyelids (ptosis). Type 2 may involve hair loss (alopecia) and enlarged parietal foramina (an enlarged opening in the parietal bones of the skull). Males with type 2 often have genital anomalies. Type 3 is associated with missing eyes (anophthalmia) or very small eyes (microphthalmia), and low-set, posteriorly rotated ears. While type 3 generally presents with the most severe facial abnormalities, the severity of the condition can vary significantly, even among individuals with the same type.

The lifespan of individuals with frontonasal dysplasia is dependent on the severity of their malformations and the success of surgical interventions in addressing related health problems, such as breathing and feeding difficulties caused by facial clefts.

Inheritance:

Frontonasal dysplasia caused by mutations in the ALX1 or ALX3 genes follows an autosomal recessive inheritance pattern. This means that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition. Parents who each carry one copy of the mutated gene typically do not exhibit signs or symptoms of the condition themselves. When mutations in the ALX4 gene cause frontonasal dysplasia, it is inherited in an autosomal dominant pattern. In this case, inheriting only one copy of the altered gene is enough to cause the disorder. Individuals may inherit the mutation from an affected parent, or the mutation may occur spontaneously, arising as a new mutation in the gene with no prior family history of the disorder.