Rothmund-Thomson syndrome.

Sir,

We describe a classic case of Rothmund-Thomon syndrome (RTS) of which only about 300 cases have been recorded in the medical literature.[1] This appropriately immunized 13-year-old boy presented with poikiloderma and absent eyebrows/eyelashes since four months of age. He was the only child born to nonconsanguineous parents after normal gestation. He would develop facial erythema and edema after a brief sun exposure, subsiding with hyperpigmentation in 2-3 days. Poikiloderma had developed over years involving the face, extremities, and buttocks in that order [Figures 1–4]. His height was 132 cm (50th centile = 156.4 cm), and he weighed 30 kg (50th centile = 45.8 kg) having WHO grade I growth retardation (height deficit 86%, weight deficit 65%). His bone age and chronological age were consistent and he showed normal mental development on Denver Development Screening Test. Systemic, ophthalmic, dental, and neurological examination, scalp hair, nails, mucosae and external genitalia were normal. He had microcytic hypochromic anemia (hemoglobin 9.3 g%) and normal serum biochemistry, urinalysis, and radio-imaging studies. Skin biopsy showed features of poikiloderma [Figure 5]. Genetic studies were not performed on account of availability and affordability concerns. With the diagnosis of RTS, genetic counseling, photoprotection and long-term follow-up were advised.

Figure 1

Poikilodermatous skin having reticulate hyperpigmentation, erythema, atrophy, telangectasias over forehead, malar area, cheeks, pinnae. Note the absence of eyebrows and eyelashes, and normal scalp hair

Figure 4

Poikilodermatous skin over buttocks

Figure 5

Histology of biopsy from buttock skin. Note poikiloderma features of hydropic degeneration of basal layer, proliferation of blood vessels, perivascular and periappendageal inflammatory infiltrate of lymphohistiocytes, melanin incontinence, and melanophages H and E, ×40

Close up view of poikilodermatous skin over face. Changes are more marked over ear pinna

Poikilodermatous skin over dorsal hands and feet

Rothmund-Thomson syndrome or poikiloderma congenitale is a rare geno-photodermatosis of autosomal recessive inheritance, featuring a DNA damage repair defect. Consanguinity is however not a constant feature. The onset is in early infancy and photodistributed poikiloderma (that becomes widespread later), premature aging, and short stature are characteristic. Sparse scalp hair, sparse or absent eyelashes/eyebrows, ophthalmic abnormalities (juvenile cataract, keratoconus, tilted optic discs, pigment deposits on cornea and conjunctiva), and skeletal abnormalities (frontal bossing, osteogensis imperfecta, saddle nose, radial ray defect) usually present heterogeneously.[2] Depending upon genetic and phenotypic heterogeneity two clinical forms may occur. RTS-I has poikiloderma, hypogonadism, juvenile cataract, and no identified gene mutation, while RTS-II shows poikiloderma and skeletal abnormalities, and is caused by homozygous or compound heterozygous (frameshift/missense) mutations in RECQL4 DNA helicase gene mapped to chromosome 8q24.3.[34] Although physical development is frequently retarded (short stature, slender and delicate limbs, small hands, bird like skull), mental development remains normal. Nearly 10-40% patients will develop bilateral juvenile cataract by 4-7 years of age and about 30% will have hypogonadism.[1] Nails may be dystrophic and hair (scalp, beard, pubic, axillary) may be sparse or absent in 50% while eyelashes/eyebrows are sparse/absent in 70% cases.[5] Dental (microdontia, early caries), gastrointestinal (esophageal/pyloric stenosis, annular pancrease, chronic emesis, diarrhea), and hematological (microcytic hypochromic anemia, leukopenia) abnormalities occur infrequently.[3] There is enhanced risk for extracutaneous (osteogenic sarcoma, myelodysplastic syndrome) and skin malignancies (squamous cell or basal cell carcinomas, malignant fibrous histiocytoma) ascribed to defective DNA repair.[5] Although life expectancy remains unaffected, ultimate prognosis depends upon development/type of malignancy. The diagnosis is mainly from characteristic clinical features as seen in our patient; photosenstivity in early infancy, photo-distributed poikiloderma becoming widespread, growth retardation, normal mental growth, absent eyelashes/eyebrows. Differentiation from other syndromes of DNA defect repair such as Bloom's syndrome or Cockayne syndrome is not difficult. Development of erythema with cafe-au-lait spots and not pokiloderma, slender built, narrow delicate face, prominent nose and high-pitched voice in Bloom's syndrome are essential differences while poikiloderma, mental retardation and dwarfism, conductive deafness, pigmentary retinopathy/blindness are hallmark features of Cockayne syndrome.[6]