Pathogenic variants in the PVRL4gene cause a multisystem disorder.
All individuals with biallelic mutations in the PVRL4gene show these features:
• Partial cutaneous syndactyly:
o Constant between toes 2–3; sometimes 4–5
o Fingers variably 2–3–4 (various combinations); never 1–2 or 4–5
• Hair abnormalities:
o Scalp hair sparse, coarse, easily broken; identical changes in eyebrows, eyelashes, and body hair
o Patchy alopecia progressing to complete loss by the 4th decade
o Hair shaft defects: pili torti-like and shaft swelling
• Dental anomalies:
o Widely spaced teeth; peg-shaped/conical crowns
o Delayed eruption, microdontia, hypodontia, and adult anodontia
o Early tooth loss
Most individuals also show these features:
• Nails
o hypoplastic nails reported in some families
• Skin (palms/soles)
o Dry, thick skin on palms/soles
o Palmoplantar hyperkeratosis progressive with age
o Reduced or absent sweat glands (in some patients)
Additional notes
• No cleft lip/palate or intellectual disability reported
• Heat intolerance (in some patients)
• Life span appears within the normal range
PVRL4