2.1 Lacrimo-Auriculo-Dento-Digital Syndrome

At least three mutations in the FGF10 gene have been found to cause lacrimo-auriculo-dento-digital (LADD) syndrome. This disorder affects the formation of the lacrimal system (the system in the eyes that produces and secretes tears), the ears, the salivary glands (the glands in the mouth that produce saliva), the teeth, the hands, and sometimes, other parts of the body. The main features of LADD syndrome are abnormal tear production, malformed ears with hearing loss, decreased saliva production, small teeth, and hand deformities.

The FGF10 gene mutations that cause LADD syndrome reduce the amount and activity of FGF10 protein. Less growth factor is available to bind to receptors, which decreases signaling within cells. A decrease in cell signaling disrupts cell maturation and development, which results in abnormal formation of the ears, skeleton, and glands in the eyes and mouth in people with LADD syndrome.

2.2 Other Disorders

Mutations in the FGF10 gene have also been found to cause a condition similar to LADD syndrome called aplasia of lacrimal and salivary glands (ALSG). Individuals with this condition have absent (aplastic) or small (hypoplastic) lacrimal glands, which secrete tears in the eyes, and aplastic or hypoplastic salivary glands. This condition often causes eye irritability, chronic tearing (epiphora), dry mouth (xerostomia), and a greater susceptibility to cavities. Sometimes, other structures that are involved in tear production are affected. The mutations that cause ALSG are thought to be less disruptive to cell signaling than the FGF10 gene mutations that cause LADD syndrome, although in rare cases, the same mutation can cause either condition. Because there is overlap between the features of ALSG and LADD syndrome and because they are caused by mutations in the same gene, it is difficult to discern whether they are distinct disorders or part of the same disease spectrum.