SNP Shot: Genomic Insights

Lacrimo-auriculo-dento-digital (LADD) syndrome is a genetic condition that primarily affects the eyes, ears, mouth, and hands. The syndrome is named for its key characteristics: problems with tear production (lacrimo-), ear abnormalities (auriculo-), dental issues (dento-), and finger or hand deformities (digital).

The lacrimal system, responsible for producing tears, is often affected in LADD syndrome. Common problems include underdeveloped or absent openings for tear ducts (lacrimal puncta) and blocked tear drainage channels (nasolacrimal duct). These issues can lead to excessive tearing (epiphora), tear sac inflammation (dacryocystitis), inflammation of the eye's surface (keratoconjunctivitis), or even the inability to produce tears.

Low-set, cup-shaped ears and hearing loss are frequently observed in individuals with LADD syndrome. The degree of hearing loss can range from mild to severe and may result from problems in the inner ear (sensorineural hearing loss), middle ear (conductive hearing loss), or a combination of both (mixed hearing loss).

Saliva production may be impaired in people with LADD syndrome due to underdeveloped or absent salivary glands. This can lead to dry mouth (xerostomia) and increase the risk of tooth decay. Dental abnormalities often include small, underdeveloped teeth with thin enamel and peg-shaped front teeth (incisors).

Hand deformities are a common feature of LADD syndrome. These may include abnormally small or missing thumbs, thumb duplication, fusion of the thumb and index finger (syndactyly), abnormal thumb placement, or a thumb with three bones instead of the usual two. Finger abnormalities can include syndactyly of the second and third fingers, extra or missing fingers, and curved pinky fingers (fifth finger clinodactyly). In some cases, the forearm may be shorter than normal, with abnormal wrist and elbow joint development that restricts movement.

Individuals with LADD syndrome may also experience other symptoms. Kidney problems, such as hardening of the kidneys (nephrosclerosis) and urine accumulation in the kidneys (hydronephrosis), can occur and impair kidney function. Recurrent urinary tract infections and genitourinary abnormalities are also possible. Some individuals may have a cleft palate (an opening in the roof of the mouth) with or without a cleft lip (a split in the upper lip). The severity and specific symptoms of LADD syndrome can vary significantly, even among family members.

Inheritance:

LADD syndrome is typically inherited in an autosomal dominant manner. This means that a mutation in just one copy of the FGFR2, FGFR3, or FGF10 gene in each cell is enough to cause the disorder. An affected person may inherit the mutation from an affected parent, or it may result from a new mutation in the gene, occurring in individuals with no family history of the condition.