SNP Shot: Genomic Insights

Oral-facial-digital (OFD) syndrome is a group of related disorders affecting the development of the mouth (oral cavity and teeth), face, and fingers and toes (digits).

Researchers have identified at least 13 different types of OFD syndrome, classified by their specific signs and symptoms. However, there is significant overlap in the features of these types, and some are not clearly defined. The classification of OFD syndrome is constantly being updated as researchers identify more affected individuals and gain a better understanding of the condition.

The symptoms of OFD syndrome vary considerably. However, most types involve developmental issues in the mouth, face, and digits. Brain abnormalities and some degree of intellectual disability are also commonly associated with most forms of the syndrome.

Oral cavity abnormalities seen in many OFD syndrome types include a split tongue (cleft tongue), an unusually shaped (lobed) tongue, and non-cancerous growths (nodules or tumors) on the tongue. Affected individuals may also have extra, missing, or malformed teeth. A cleft palate (an opening in the roof of the mouth) is another common feature. Some individuals with OFD syndrome have bands of extra tissue (hyperplastic frenula) that abnormally connect the lip to the gums.

Distinctive facial features frequently associated with OFD syndrome include a split lip (cleft lip), a wide nose with a broad, flat nasal bridge, and widely spaced eyes (hypertelorism).

Digit abnormalities in OFD syndrome can affect both fingers and toes. These include the fusion of certain fingers or toes (syndactyly), unusually short digits (brachydactyly), or digits that are abnormally curved (clinodactyly). The presence of extra digits (polydactyly) is also common in most types of OFD syndrome.

Other features are specific to only one or a few types of OFD syndrome. These help to differentiate the various forms of the disorder. For example, the most common type, OFD syndrome type I, is associated with polycystic kidney disease. This kidney disease involves the growth of fluid-filled sacs (cysts) that impair the kidneys' ability to filter waste from the blood. Other OFD syndrome types are characterized by neurological problems, specific brain structure changes, bone abnormalities, vision loss, and heart defects.

Inheritance:

OFD syndrome type I is inherited in an X-linked dominant manner. The responsible gene is located on the X chromosome, one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in just one copy of the gene in each cell is enough to cause the condition. Some cells produce a normal amount of OFD1 protein, while others produce none. This overall reduction in OFD1 protein leads to the signs and symptoms of OFD syndrome type I. In males (who have only one X chromosome), mutations result in a complete loss of the OFD1 protein. This lack of protein is usually fatal very early in development, so very few males are born with OFD syndrome type I. Affected males typically die before birth, although some have survived into early infancy. Most other forms of OFD syndrome are inherited in an autosomal recessive manner, meaning that both copies of a causative gene in each cell must have mutations for the condition to develop. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they usually do not show signs or symptoms of the condition themselves.