Rothmund-Thomson Syndrome

Rothmund-Thomson syndrome is a rare autosomal recessive disorder with poikiloderma that appears in infancy, short stature, skeletal anomalies and a risk of osteosarcoma and skin cancer. Type 2, caused by RECQL4 variants, carries the bone cancer risk, while type 1, associated with ANAPC1 variants, causes juvenile cataracts.

Pathophysiology. RECQL4 encodes a RecQ helicase involved in DNA replication and repair. Loss causes genomic instability, especially in the skeleton and skin.

The rash begins at 3 to 6 months of age on the cheeks and spreads to the limbs and buttocks, sparing the trunk and abdomen.

Overlapping disorders (RAPADILINO and Baller-Gerold syndrome) share RECQL4 variants.

• Poikiloderma: erythema, telangiectasia, reticulated hyperpigmentation and atrophy from the first months
• Sparse scalp hair, eyebrows and eyelashes
• Short stature, small hands and feet
• Skeletal anomalies: radial ray defects, absent or hypoplastic thumbs and patellae, craniosynostosis
• Juvenile cataracts (type 1)
• Dental anomalies and hyperkeratosis of the palms and soles
• Osteosarcoma in adolescence (type 2), and squamous cell carcinoma of the skin
• Hypogonadism and gastrointestinal symptoms in some

• Clinical diagnosis: typical poikiloderma in a child, with skeletal anomalies and sparse hair.
• Genetic testing of RECQL4 (and ANAPC1) with deletion and duplication analysis.
• Skeletal survey at diagnosis to detect radial ray anomalies and bone lesions.
• Eye examination for cataracts.
• Bone pain evaluation by imaging and biopsy when a lesion is suspected.
• Skin biopsy for chronic ulcers or nodules.

Differential diagnosis.

• Bloom syndrome
• Dyskeratosis congenita
• Poikiloderma with neutropenia
• Kindler syndrome
• Cockayne syndrome and xeroderma pigmentosum
• Werner syndrome

• Sun protection: sun protection factor 50 or more and clothing, since sun exposure worsens poikiloderma and raises skin cancer risk.
• Cutaneous treatment: pulsed dye laser for telangiectasia and erythema, repeated at 4 to 8 week intervals, and emollients for dry hyperkeratotic skin.
• Osteosarcoma vigilance: educate families to report bone pain, swelling or a limp promptly. Evaluate with plain radiograph and MRI. No routine scheduled imaging of the whole skeleton is proven, so clinical review at least every 6 months is used. Treatment is surgery with chemotherapy, using the usual drugs at reduced intensity where toxicity or radiation sensitivity is a concern, and avoiding radiotherapy where possible.
• Skin cancer: examination every 6 to 12 months from adolescence, with excision of suspicious lesions.
• Cataract surgery for visual impairment.
• Orthopaedic care: correction of limb anomalies, and craniosynostosis surgery when indicated.
• Dental and dermatological care: dental review, and keratolytic creams (urea 10% cream twice daily) for palmoplantar keratoderma.
• Endocrine care: growth assessment and pubertal review, with sex steroid replacement for hypogonadism.
• Genetic counselling: each sibling has a 25% chance of being affected.

Special groups.

• Children with RECQL4 variants: higher osteosarcoma risk in adolescence, so earlier education and review are given.

Monitoring. Clinical review every 6 months with skin and skeletal examination. Annual eye examination, growth and pubertal assessment.

Referral and escalation. Refer to clinical genetics, dermatology and paediatric orthopaedics oncology. Urgent for persistent bone pain, a bone mass, or a changing or ulcerated skin lesion.