AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Background

Rothmund-Thomson syndrome, or poikiloderma congenitale, is a rare autosomal recessive disorder attributed to mutations of the RECQL4 helicase gene on 8q24. Key features include early photosensitivity and poikilodermatous skin changes, juvenile cataracts, skeletal dysplasias, and a predisposition to osteosarcoma and skin cancer.

Frequency

International

Approximately 300 cases have been reported in the scientific literature.

Sex

Whether Rothmund-Thomson syndrome has a predilection for one sex over the other is unclear. An equal female-to-male ratio, a female predominance (1.4:1), and a male predominance (2:1) have all been reported in various case series.

Age

More than 90% of patients develop the initial skin manifestations during the first year of life, usually from age 3-6 months. Rarely, the skin changes may be present at birth, or they may appear as late as age 2 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

History

Patients generally present with a skin rash (poikiloderma), small stature, and skeletal dysplasias.

• The characteristic skin findings are the most consistent feature of the syndrome.
• • The acute phase begins in early infancy as red patches or edematous plaques, sometimes with blistering. The cheeks are usually first involved, with later spread to other areas of the face, the extremities, and the buttocks.
  • Over months to years, the rash enters a chronic stage characterized by poikiloderma (atrophy, telangiectasias, and pigmentary changes).
• Photosensitivity is a feature in more than 30% of cases.

Physical

• Irregular erythema and edema of the skin is replaced by reticulated red-brown patches associated with punctate atrophy and telangiectasias (poikiloderma). These characteristic skin changes are typically seen on the face, extensor extremities, and buttocks with sparing of the chest, abdomen, and back.
• Acral hyperkeratotic lesions on the elbows, knees, hands, and feet can be seen at puberty. Palmar keratoderma has been reported.
• Patients may have sparse hair, premature canities, and dystrophic or atrophic nails.
• Dental abnormalities include malformation, microdontia, and failure of eruption.
• Juvenile cataracts have been reported in as many as 40-50% of patients aged 4-7 years.
• Patients usually have short stature, which ranges from dwarfism to a small build. About one half of patients have skeletal abnormalities, most frequently a characteristic facies with frontal bossing, saddle nose, and micrognathia. Small hands and feet disproportionate to the patient's body size are observed in 20% of patients. Approximately 10% of patients have absent or malformed radii, and 5% of patients have absent or partially formed thumbs.
• Sexual abnormalities, affecting about 25% of adult patients, include hypoplasia and/or aplasia of the external genitalia, amenorrhea, lack of secondary sex characteristics, and infertility.
• Celiac disease has been reported.

Causes

The disorder has been attributed to mutations of the RECQL4 gene on 8q24, which encodes a RecQ DNA helicase. A strong correlation appears to exist between the presence of truncating mutations of the RECQL4 gene and the development of osteosarcoma.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Other Problems to be Considered

Acrogeria (Gottron syndrome), an autosomal recessive disease, is characterized by acral poikiloderma in infancy and lipoatrophy.

Acrokeratotic poikiloderma of Weary, which probably is an autosomal dominant disease, is characterized by a widespread eczematous dermatitis and acral bullae in infancy, with the later development of keratoses.

Bloom syndrome, an autosomal recessive disease, is characterized by telangiectases and light sensitivity with erythema on the face and other sun-exposed areas. Patients with Bloom syndrome do not have a true poikiloderma.

Patients with Cockayne syndrome develop a photodistributed erythema, atrophy, and hyperpigmentation.

Patients with dyskeratosis congenita develop reticulated hyperpigmentation or hypopigmentation on the face, the neck, the trunk, and the thighs.

Erythropoietic protoporphyria causes erythematous, edematous, photodistributed plaques after exposure to ultraviolet light.

Fanconi anemia, an autosomal recessive disease, is characterized by generalized, dusky, olive-brown pigmentation that is most intense on the lower part of the trunk, in the flexures, and on the neck in 85% of patients; pancytopenia; and skeletal malformations, including aplasia or hypoplasia of the thumb, metacarpal, or radius, in 60% of patients.

Kindler syndrome, a disease with an unknown inheritance pattern, is characterized by acral bullae at birth and after minor trauma, acral hyperkeratosis, mucous membrane fragility with esophageal and urethral strictures, and webbing of the fingers and the toes.

Lupus erythematosus may present with a characteristic butterfly facial erythema.

Mendes da Costa syndrome, an X-linked recessive disease, is characterized by alopecia and generalized bullae in infants; poikiloderma develops later.

Sclerosing poikiloderma of Weary, an autosomal dominant disease, is characterized by sclerodermatous palms and soles.

Patients with Werner syndrome develop sclerodermoid changes on acral areas, with mottled hyperpigmentation, telangiectasias, and premature canities.

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Imaging Studies

• Baseline skeletal radiographs of the long bones by age 5 years are recommended due to the high frequency of skeletal dysplasias.

Histologic Findings

Histologic examination of poikilodermatous skin in children reveals a flattened, atrophic epidermis with derma-epidermal junction edema and dermal vasodilatation, possibly with a perivascular lymphocytic infiltrate. Adult skin in exposed areas reveals patchy Bowenoid dyskeratosis in the epidermis and fragmented dermal elastic tissue.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Medical Care

• Sunscreens with UVA and UVB coverage should be applied regularly.
• Keratolytics and retinoids have been somewhat successful in treating the hyperkeratotic lesions.

Surgical Care

• Telangiectases can be treated with pulsed-dye laser therapy.

Consultations

• Consultation with an ophthalmologist is recommended for annual eye examinations to screen for the development of juvenile cataracts.
• Referrals to a dentist, an orthopedist, an endocrinologist, and a hematologist/oncologist may be indicated based on the related signs and symptoms.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Retinoids

These agents decrease the cohesiveness of abnormal hyperproliferative keratinocytes, and they may reduce the potential for malignant degeneration. They also modulate keratinocyte differentiation.

Drug Category: Keratolytic

This agent causes cornified epithelium to swell, soften, macerate, and then desquamate.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Complications

• Osteosarcomas have been reported to arise in as many as 32% of patients. They most frequently arise in the tibia/fibula.
• The development of nonmelanoma skin cancers, with an earlier onset than that of the general population, has also been reported. The majority of cases were either Bowen disease or squamous cell carcinoma. Squamous cell carcinoma may develop in acral keratoses.

Prognosis

• In the absence of malignancy, patients usually have a normal life span.

Patient Education

• Patients and their families should be educated regarding the potential signs and symptoms of osteosarcoma such as bone pain, swelling, or an enlarging lesion on a limb.
• The use of broad-spectrum photoprotection should be emphasized. Monitoring for nonhealing, ulcerated, or enlarging skin lesions suggestive of malignancy should also be encouraged.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Media file 1:  Note the poikiloderma and skeletal abnormalities.
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Media type:  Photo

Media file 2:  Close-up of poikiloderma.
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Media type:  Photo

Media file 3:  Close-up of poikiloderma.
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Media type:  Photo

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

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• Geronemus RG. Treatment of the cutaneous vascular component of the Rothmund-Thomson syndrome. Pediatr Dermatol. Mar-Apr 1996;13(2):175. [Medline].
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• Kitao S, Lindor NM, Shiratori M, et al. Rothmund-thomson syndrome responsible gene, RECQL4: genomic structure and products. Genomics. Nov 1 1999;61(3):268-76. [Medline].
• Larizza L, Magnani I, Roversi G. Rothmund-Thomson syndrome and RECQL4 defect: splitting and lumping. Cancer Lett. Jan 28 2006;232(1):107-20. [Medline].
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• Macris MA, Krejci L, Bussen W, et al. Biochemical characterization of the RECQ4 protein, mutated in Rothmund-Thomson syndrome. DNA Repair (Amst). Feb 3 2006;5(2):172-80. [Medline].
• Moss C. Rothmund-Thomson syndrome: a report of two patients and a review of the literature. Br J Dermatol. Jun 1990;122(6):821-9. [Medline].
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• Nanda A, Kanwar AJ, Kapoor MM, et al. Rothmund-Thomson syndrome in two siblings. Pediatr Dermatol. Dec 1989;6(4):325-8. [Medline].
• Piquero-Casals J, Okubo AY, Nico MM. Rothmund-thomson syndrome in three siblings and development of cutaneous squamous cell carcinoma. Pediatr Dermatol. Jul-Aug 2002;19(4):312-6. [Medline].
• Popadic S, Nikolic M, Gajic-Veljic M, Bonaci-Nikolic B. Rothmund-Thomson syndrome. The first case with plantar keratoderma and the second with coeliac disease. Acta Dermatovenerol Alp Panonica Adriat. Jun 2006;15(2):90-3. [Medline].
• Prendiville JS, Fine JD, Esterly NB. Kindler syndrome and epidermolysis bullosa simplex. J Am Acad Dermatol. Aug 1990;23(2 Pt 1):327-8. [Medline].
• Roth DE, Campisano LC, Callen JP, et al. Rothmund-Thomson syndrome: a case report. Pediatr Dermatol. Dec 1989;6(4):321-4. [Medline].
• Uhring M, Poterszman A. [DNA helicases and human diseases.]. Med Sci (Paris). Dec 2006;22(12):1087-94. [Medline].
• Vennos EM, Collins M, James WD. Rothmund-Thomson syndrome: review of the world literature. J Am Acad Dermatol. Nov 1992;27(5 Pt 1):750-62. [Medline].
• Wang LL, Gannavarapu A, Kozinetz CA, et al. Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J Natl Cancer Inst. May 7 2003;95(9):669-74. [Medline].
• Wang LL, Levy ML, Lewis RA, et al. Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients. Am J Med Genet. Jul 22 2001;102(1):11-7. [Medline].
• Werner SR, Prahalad AK, Yang J, Hock JM. RECQL4-deficient cells are hypersensitive to oxidative stress/damage: Insights for osteosarcoma prevalence and heterogeneity in Rothmund-Thomson syndrome. Biochem Biophys Res Commun. Jun 23 2006;345(1):403-9. [Medline].
• Woo LL, Futami K, Shimamoto A, et al. The Rothmund-Thomson gene product RECQL4 localizes to the nucleolus in response to oxidative stress. Exp Cell Res. Oct 15 2006;312(17):3443-57. [Medline].

Article Last Updated: Feb 28, 2007