DISEASE CARD

Disease group Ectodermal Dysplasia
DISEASE NAME ROTHMUND-THOMSON SYNDROME
Synonymous RTS; Poikiloderma Congenitale
Estimated prevalence more than 300 cases reported in the literature
OMIM 268400
Inheritance Autosomal Recessive
Gene (s) RECQL4 (603780)

Definition

Rothmund Thomson syndrome (RTS) is a rare autosomal recessive disorder first reported by Rothmund in 1868. The characteristic cutaneous feature is poikiloderma, comprising skin atrophy, pigmentation and telangiectasia. In addition, affected individuals present with abnormalities of the eyes, nose, bones, hair, teeth, gastrointestinal tract and reproductive organs. There are reports of an increased prevalence of osteosarcoma and skin cancer in affected individuals.

Clinical Description

Patients present in infancy with photosensitivity and poikilodermatous skin changes over the cheeks, limbs and buttocks. Multiple developmental abnormalities also include hypodontia, saddle-shaped nose, micrognathia, juvenile cataracts, sparse hair, short stature, anaemia, gastrointestinal tract (abnormalities may include chronic diarrhoea, vomiting, pyloric stenosis) and hypogonadism. Congenital long bone defects are a frequent feature and osteogenic sarcoma has been reported in up to one third of affected individuals (most commonly the tibia and fibula). Pujol et al. has suggested that a diagnosis of RTS be considered in all patients with osteogenic sarcoma, particularly if associated with skin changes.

Pathogenesis

The defective gene in RTS was identified by Kitao et al. in 1999 as the helicase gene RECQL4 on 8q24. Mann et al. (2005) created a viable Recql4-mutant mouse model and suggested that RECQL4 may play a role chromosomal instability which may be the underlying cause of cancer predisposition and birth defects in affected mice.

Diagnosis

Diagnosis is made by at, or soon after, birth with the onset of an acute erythematous (occasionally blistering) rash which may present initially on the cheeks and subsequently on limbs and buttocks. This is later replaced by photosensitivity and poikiloderma. Genomic DNA may be analysed for a RECQL4 gene mutation which may confirm the diagnosis in some cases and assist with genetic counselling. No other diagnostic tests are available at present.

Treatment

The management of the RTS requires expertise from various medical and surgical specialties. It is recommended that baseline skeletal radiographs of the long bones be performed by the age of 5 years for all patients. Dental treatment is extremely important as many require successive dentures as a child with addition of dental implants and bridges later in adult life. Patients require photoprotection with regular application of sunscreen with UVA and UVB coverage. Yearly ophthalmological review is required for assessment of juvenile cataracts.