SNP Shot: Genomic Insights

Otopalatodigital syndrome type 2 (OPD2) is a genetic condition that primarily affects skeletal development. It belongs to a group of related disorders known as otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, frontometaphyseal dysplasia, Melnick-Needles syndrome, and terminal osseous dysplasia. These disorders commonly involve hearing impairment due to malformed ossicles (tiny ear bones), palate development issues, and skeletal abnormalities affecting the fingers and toes (digits). OPD2 can also affect other parts of the body, including the brain and heart.

Individuals with OPD2 often display distinctive facial features, such as widely spaced and downward-sloping eyes, prominent brow ridges, a wide, flat nose, and a small lower jaw and chin (micrognathia). They may also have finger and toe abnormalities like curved fingers (camptodactyly) and shortened or missing thumbs and big toes. Short stature, bowed arm and leg bones, and other bone abnormalities or absences are also typical. Underdeveloped ribs can lead to breathing difficulties. Some individuals may have a cleft palate or experience hearing loss.

Besides skeletal issues, those with OPD2 may experience developmental delays, increased fluid in the brain (hydrocephalus), abdominal organs protruding through the navel (omphalocele), heart defects, chest abnormalities, blocked ducts between the kidneys and bladder (ureteral obstruction), and in males, the urethra opening on the underside of the penis (hypospadias).

Males with OPD2 tend to have more severe symptoms than females. Sadly, affected males often do not survive beyond infancy due to respiratory failure caused by an underdeveloped rib cage.

Inheritance:

OPD2 follows an X-linked inheritance pattern. This means the mutated gene responsible for the condition is located on the X chromosome, one of the two sex chromosomes. Males, possessing only one X chromosome, develop the condition if that single copy has the mutation. Females, with two X chromosomes, may have milder symptoms or no symptoms at all if only one X chromosome carries the mutated gene. A key characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.