OMIM ID:
Rothmund-Thomson Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Patients have been reported with juvenile and infantile cataracts. Reported prevalence varies possibly because the diagnostic criteria have not been established and more than one disorder may be represented by the title. Rothmund (an ophthalmologist) originally reported two families of 5 children in which lens opacities were found, but Thomson, who was a dermatologist, in a later report did not mention cataracts. The lens opacities are usually nuclear or posterior cortical in location and may be evident in 50% of patients. Iris stromal changes such as hypoplasia have also been reported. Eyelashes and/or eyebrows may be sparse. This is likely the same disorder as the previously described ‘mesodermal dysgenesis of the iris and skeletal dysplasia’ and formerly listed as 270240 in OMIM.
Systemic Features
This is a clinically heterogeneous disorder. Skin atrophy with pigmentary changes, telangiectasia, short stature, premature aging, and skeletal abnormalities are characteristic. There is an increased risk of malignancy, particularly osteosarcomas and skin cancer. Saddle nose, sparse hair, hypogonadism, dysplastic nails, and teeth anomalies have also been described.
The skin is usually normal at birth but an erythematous rash typically appears in the first six months of life accompanied by swelling and blistering. Eventually areas of hypo- and hyperpigmentation appear in a reticulated pattern with spots of punctate atrophy and telangiectasia. Hyperkeratosis of the soles of the feet is common. The skeletal abnormalities of dysplasia, radial ray defects, and missing bones are often evident at birth while osteopenia and delayed bone maturation are evident later.
Genetics
Inheritance
This is an autosomal recessive disorder in which most patients have mutations in the RECQL4 gene (8q24.3).
Mutations in the same gene cause Baller-Gerold syndrome (218600) suggesting that the two disorders are allelic but the phenotypes are considerably different.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.