Congenital absence of nail involving several digits is rare. Isolated anonychia can be inherited as a dominant, recessive, or sporadic abnormality. Underlying bone abnormalities are often present. Other associated findings include broad, small hands due to skeletal anomalies such as loss of phalanges or isolated fingers and toes (ectrodactyly), syndactyly, or polydactyly.

Patients with nail-patella syndrome, ectodermal dysplasia, anonychia–lymphedema, DOORS syndrome, and Iso-Kikuchi syndrome have anonychia and severe skeletal defects. Dyskeratosis congenita is characterized by bone marrow failure, reticulate pigmentation, nail dystrophy, and oral leukoplakia. Anonychia can be seen in children. Absence of nail may be confined to thumbs and great toes or on the fifth finger in Coffin-Siris syndrome. Use of alcohol, morphine, and antiepileptics in pregnancy has been associated with hyponychia and anonychia.

Anonychia has been linked to chromosome 20p13. Homozygous or compound heterozygous mutations in the gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, have been identified, suggesting that RSPO4 has a crucial role in nail morphogenesis.