Rothmund-Thomson syndrome type 1

Rothmund-Thomson syndrome type 1 (RTS1) is an extremely rare autosomal recessive genodermatosis caused by biallelic pathogenic variants in the ANAPC1 gene, which encodes a subunit of the anaphase-promoting complex. RTS1 is distinguished from Rothmund-Thomson syndrome type 2 (caused by RECQL4 mutations) primarily by its clinical features. The hallmark feature shared across RTS subtypes is poikiloderma — a characteristic skin condition that typically appears in infancy, presenting as redness, swelling, and blistering on the cheeks that progressively evolves into a pattern of skin atrophy, telangiectasias (small dilated blood vessels), and areas of increased and decreased pigmentation. In RTS1, poikiloderma is accompanied by juvenile cataracts, which are a distinguishing feature of this subtype, along with skeletal abnormalities, short stature, sparse hair, sparse or absent eyelashes and eyebrows, and dental anomalies. Unlike RTS type 2, RTS type 1 is not typically associated with an increased risk of osteosarcoma or other cancers. The condition primarily affects the skin, eyes, skeletal system, and ectodermal structures (hair, teeth, nails). Growth retardation may be evident prenatally or in early childhood. Photosensitivity is common, and patients are advised to practice strict sun protection. There is currently no cure for Rothmund-Thomson syndrome type 1. Management is supportive and multidisciplinary, involving dermatologists, ophthalmologists, orthopedic specialists, and geneticists. Early ophthalmologic surveillance is critical for timely detection and surgical management of cataracts. Sun protection measures are recommended to minimize skin damage. Growth monitoring, dental care, and management of skeletal complications are also important components of ongoing care. Genetic counseling is recommended for affected families.

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