Rothmund-Thomson Syndrome

Rare recessive syndrome with bullous extensive skin anomalies, juvenile cataract skeletal disorders, and malignancy predisposition (skin and osseous). Trisomy 8 mosaicism is frequent. Trisomy 8 occurs in 2.5% of the peripheral lymphocytes. This low incidence could be overlooked in routine karyotyping. Maintaining hydration is a major concern.

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Poikiloderma Atrophicans and Cataract; Poikiloderma Congenitale.

Fewer than 100 cases described.

Autosomal recessive; variable phenotype; mutations in a recQ helicase gene (RECQL4) at locus 8q24.3 in several patients.

The DNA helicase gene RECQL4 is involved in this syndrome. In vivo clonal chromosomal re-arrangements causing an acquired somatic mosaicism have been evocated to explain this pathology.

Clinical, evocated by the association of skin abnormalities (starting in infancy), skeletal disorders, juvenile cataract, and predisposition to malignancy and characteristic rash. Karyotype may show abnormalities of chromosome 8 in a minority of patients.

The skin changes begin within the first year of life in 89% of patients. These are defined as erythematous patches or red edematous plaques, sometimes accompanied by blistering. Characteristically, these begin on the cheek and spread to the forehead, ears, and neck. Usually by this time, erythema has also appeared on the dorsal aspects of the hands, extensor aspects of the arms and forearms, and the legs and buttocks. Poikiloderma is a feature of atrophy, areas of hyperand hypopigmentation, and telangiectases. Skin, nails, and hair are primarily involved: erythematous or bullous skin lesions, poikiloderma (atrophic plaques with telangiectasia), telangiectasia, skin atrophy, sun sensitivity (35%), abnormal scar formation, atrophic nails (24%), sparse hair, alopecia. Premature graying of hair can frequently be observed and may be associated with short stature (54%), mental retardation, and facial deformation: frontal bossing, prognathism, small saddle nose, dental and ocular anomalies (juvenile zonular cataracts [52%], microphthalmia, microcornea, strabismus, glaucoma). Skeletal repercussions also concern limbs with osteoporosis, forearm reduction defects, absence of patella joint, contractures, thumb hypoplasia, small hands, and small and club feet. Other clinical features are occasional and can affect digestive area (annular pancreas, anterior positioning of the anus, duodenal stenosis) and genitourinary structures (hypogonadism, cryptorchidism nephritis or nephropathy with vascular hypertension). Anemia, growth hormone deficiency, and immunoglobulin abnormality have also been reported. There is an increased risk of basal cell carcinoma, squamous cell carcinoma, and osteogenic sarcoma. Treatment includes constant use of sunscreen and avoidance of sun exposure. Regular ophthalmic screening and evaluation of any bone pain are mandatory. One case was described with Addison disease and one case was described with growth hormone deficiency.

Good medical history and physical examination must be obtained to exclude obvious Addison disease. Look carefully at the future emplacement of the intravascular infusion lines. Special attention to the teeth (implantation and looseness). Creatinine and urea levels are useful in the presence of hypertension. Check preoperative hemoglobin. A complete evaluation of intravascular volemia and electrolytes status (risk of dehydration as a consequence of skin lesions and nephropathy) and high blood pressure consequences (ECG, echocardiography, renal echography). Laboratory investigations should include natremia, kalemia, calcemia, urea, creatinine, growth hormone, and hematocrit.

Careful intraoperative positioning and skin protection is necessary. Consider a smaller endotracheal tube than expected because of the presence of short stature and delayed physical development. The presence of loose teeth will require special attention during direct laryngoscopy for tracheal intubation. Also, special attention will be needed even for placement of a laryngeal mask airway where dislodgment of a tooth or teeth could be catastrophic. Vascular access placement can be difficult because of the presence of skin lesions. Proper pressure point and padding, careful positioning is essential and avoiding the use of sticky tapes is important. Blood pressure cuff should be padded to limit chances of provoking skin lesions. Intraoperative fluid regimen should be controlled carefully because of the association of nephropathy (over-hydration) and the risk of dehydration (hypoor anhydrosis).

Prophylactic antibiotics should be used because of the high incidence of immunodeficiency in these patients, leading to a high risk of infection. Avoid parasympatholytic drugs (dyshidrosis). Avoid succinylcholine in the presence of glaucoma.

Werner Syndrome: Progressive disorder characterized by progeria-like appearance. Although the age of onset is the third or fourth decades of life, certain clinical features can be present during childhood, adolescence, and early adulthood. Children often appear unusually small for age because of an abnormally slow growth rate. By the mid-20s, affected individuals have alopecia. Bilateral senile cataracts, osteoporosis, hypogonadism, diabetes mellitus type II, and generalized atherosclerosis. It is inherited as an autosomal recessive trait.

Cockayne Syndrome: Characterized by dwarfism, distinctive skin abnormalities and craniofacial malformations, and a progeria-like appearance. Other clinical features include optic nerve atrophy, retinal degeneration, and cataracts. The skin may be abnormally sensitive to sunlight, leading to scarring, abnormal pigmentation, and atrophy of affected areas. Characteristic facial abnormalities include a thin nose, sunken eyes, and prognathism. It is inherited as an autosomal recessive trait.

Ectodermal Dysplasias, Ectrodactyly, and Macular Dystrophy (EEM) Syndrome: Skin rashes, impaired healing of the skin, sparse or absent hair, dental defects, craniofacial malformations, ocular abnormalities, dwarfism, can also be considered similar to those associated with Rothmund-Thomson Syndrome.

Bloom Syndrome: Characterized by dwarfism and distinctive skin abnormalities of the facial area. The facial lesions are described as abnormally red, inflamed areas resembling erythema (sunburn), photosensitivity, and telangiectasia (typically, referred to as “butterfly” pattern across the cheeks and the nose). Other craniofacial features include malar hypoplasia, mandible hypoplasia, a prominent nose. Leukemia is believed to be more frequent.