The main clinical features of the disease include:
Oral abnormalities: abnormal, missing, or supernumerary teeth, tongue anomalies (including hamartomas and/or bifid and lobulated tongue), and hyperplastic oral frenulae. Clefts of the upper lip and the palate are also reported, as well as thickened alveolar ridges.
Facial Abnormalities: Dysmorphic features include facial asymmetry, down-slanting palpebral fissures, hypertelorism, micrognathia, a broadened nasal ridge, hypoplasia of the alae nasi, and frontal bossing. Evanescent milia of the face and ears, which usually disappear before the third year of life are commonly associated, as well as dryness, brittleness, and/or alopecia of the scalp hair.
Skeletal defects: Limb abnormalities are present in over 80% of patients and include syndactyly, brachydactyly, clinodactyly, duplication of the hallux (unilateral), and, more rarely, pre- or postaxial polydactyly. Hands are more affected than feet. Skeletal manifestations have been reported in a few patients, including an increase in the nasion-sella-basion (cranial base) angle. Also metacarpal shortening, tibial dysplasia/shortening, and hip dysplasia has been rarely reported.
Central Nervous System (CNS) involvement: CNS involvement is observed in about 50% of cases and includes malformations that comprise a heterogeneous spectrum, including agenesis of the corpus callosum, intracerebral single or multiple epithelial or arachnoidal cysts, porencephaly, heterotopia of the gray matter, cerebellar malformation, abnormal gyration, and microcephaly. In rare cases hypothalamic hamartoma leading to precocious puberty has been described. Mental retardation (mild to moderate) has been observed in about 50% of patients and decreased hearing acuity has been reported in a few cases.
Cystic disease: Polycystic kidney disease is associated with OFDI syndrome in over 35% of cases with reports of patients in whom renal involvement completely dominates the clinical course of the disease. Histochemical analyses of cystic renal tissues from patients with OFDI syndrome demonstrate a predominantly glomerulocystic kidney disease with a minor population of cysts derived from distal tubules. The age of onset of cystic kidney in OFDI patients is most often in adulthood (second and third decades), but cysts resulting in early renal failure have occasionally been described in children in the first decade of life. In addition to renal cysts, pancreatic, ovarian, and liver cysts have been described.