Pathogenic variants in the PVRL1gene cause a multisystem disorder.
All individuals with biallelic mutations in the PVRL1gene show these features:
• Ectodermal hair abnormalities
o Hypotrichosis with short, brittle scalp hair
o Scant/sparse lateral eyebrows and sparse eyelashes
• Dental anomalies
o Delayed eruption; microdontia; hypodontia
o Adult anodontia reported in many affected
• Characteristic craniofacial appearance
o Triangular face with malar hypoplasia
Most Individuals also show these features:
• Orofacial clefting
o Cleft lip and/or cleft palate
o When cleft is absent, an abnormal philtrum may be noted
• Cutaneous syndactyly
o Toes: constant between 2–3; sometimes 4–5
o Fingers: various combinations among 2–3–4; never 1–2 or 4–5
• Skin, palms/soles
o Dry, thick skin with palmoplantar hyperkeratosis that progresses with age
• Nails
o Usually normal; onychodysplasia can occur
Additional notes
• Sweating: Often reported as normal; hypohidrosis has been described in some cases.
• Neurodevelopment & severity: Cognitive outcome varies by family. Severe forms (reported in Israeli and Brazilian families) included intellectual disability and increased infant mortality; a milder “Margarita Island” form shows normal intelligence and normal life span, with some individuals lacking clefting and syndactyly.
• A high carrier frequency on Margarita Island has been hypothed to reflect heterozygote resistance to alpha herpes virus infection.
PVRL1