Rothmund-Thomson Syndrome

Updated: Jun 18, 2018
Author: Sylvia Hsu, MD; Chief Editor: Dirk M Elston, MD 



Rothmund-Thomson syndrome, or poikiloderma congenitale, is a rare autosomal recessive disorder attributed to mutations of the RECQL4 helicase gene on 8q24.[1, 2, 3] Key features include early photosensitivity and poikilodermatous skin changes, juvenile cataracts, skeletal dysplasias, and a predisposition to osteosarcoma and skin cancer.[4, 5]


Rothmund-Thomson syndrome (poikiloderma congenitale) has been attributed to mutations of the RECQL4 gene on 8q24, which encodes a RecQ DNA helicase.[1, 2, 3, 6, 7] RecQ helicases are enzymes that function in DNA replication and repair and appear to be essential for the maintenance of genomic stability.[8, 9, 10, 11, 12, 13, 14, 15, 16] A strong correlation appears to exist between the presence of truncating, loss-of-function mutations of the RECQL4 gene, and the development of skeletal abnormalities and osteosarcoma.



Approximately 300 cases of Rothmund-Thomson syndrome (poikiloderma congenitale) have been reported in the scientific literature worldwide.


Whether Rothmund-Thomson syndrome (poikiloderma congenitale) 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.


More than 90% of patients with Rothmund-Thomson syndrome (poikiloderma congenitale) 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.


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.




Patients with Rothmund-Thomson syndrome (poikiloderma congenitale) generally present with a 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.

Gastrointestinal problems such as chronic emesis or diarrhea may occur in infancy and early childhood but usually resolve spontaneously. Celiac disease has been reported.[17]

Hematological abnormalities ranging from isolated anemia and neutropenia to myelodysplasia and leukemia have also been noted to occur.

Physical Examination

In Rothmund-Thomson syndrome (poikiloderma congenitale), 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. See the images below.

Note the poikiloderma and skeletal abnormalities. Note the poikiloderma and skeletal abnormalities.
Close-up of poikiloderma. Close-up of poikiloderma.
Close-up of poikiloderma. Close-up of poikiloderma.

Acral hyperkeratotic lesions on the elbows, knees, hands, and feet can be seen at puberty. Palmar keratoderma has been reported.[17]

Patients may have sparse scalp hair, eyelashes, and eyebrows. Premature canities may also be observed.

Nail abnormalities such as dystrophic or atrophic nails may be seen.

Dental abnormalities include malformation, microdontia, and failure of eruption.

Juvenile cataracts have been reported to occur with a prevalence that has been estimated at less than 10% in some series and as high as 40-50% in others. Most develop between age 3 and 7 years.

Patients usually have short stature, which ranges from dwarfism to a small build. More than half of patients have skeletal abnormalities, most frequently a characteristic facies (with frontal bossing, saddle nose, and micrognathia), disproportionately small hands and feet, absent or malformed radii, and 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.

Otsu et al report a patient who had some uncommon complications of Rothmund-Thomson syndrome (poikiloderma congenitale) and many typical features, but the patient did not have a mutation in RECQL4; therefore, they suggest this case was a "peculiar" variant of Rothmund-Thomson syndrome.[18]


Osteosarcomas have been reported to arise in as many as 32% of patients with Rothmund-Thomson syndrome (poikiloderma congenitale). They most frequently arise in the tibia/fibula. The development of osteosarcoma among patients with the syndrome has been strongly correlated with truncating mutations of RECQL4.[19]

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.[20] Squamous cell carcinoma may develop in acral keratoses.

While most skin cancers reported in patients with Rothmund-Thomson syndrome (poikiloderma congenitale) have been nonmelanoma skin cancers; Howell and Bray reported the occurrence of an amelanotic melanoma in a young woman with Rothmund-Thomson syndrome (poikiloderma congenitale).[21]



Diagnostic Considerations

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

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, an autosomal recessive disorder, 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. Acrokeratotic poikiloderma of Weary, which probably is an autosomal dominant form of Kindler syndrome, is characterized by a widespread eczematous dermatitis and acral bullae in infancy, with the later development of acral keratoses.[22]

Poikiloderma with neutropenia is an autosomal recessive disorder characterized by generalized poikiloderma, short stature, nail dystrophy, and neutropenia.

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.

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

Differential Diagnoses



Genetic Testing

By sequence analysis of RECQL4, a disease-causing mutation can be identified in approximately 66% of individuals diagnosed with Rothmund-Thomson syndrome.[5, 23] Although the sensitivity of the genetic test is 66%, the clinical specificity approaches 100%; thus a negative test does not rule out the diagnosis of Rothmund-Thomson syndrome but a positive test is confirmatory.

A Clinical Utility Gene Card for Rothmund-Thomson syndrome, published in 2012, summarizes guidelines for the use of genetic testing for the syndrome using mutational analysis of the RECQL4 gene.[24] In classic cases, a correct diagnosis may be made on clinical findings (such as early-onset facial poikiloderma accompanied by radial-ray defects, growth defects, and sparse hair). Genetic testing of the RECQL4 gene is of particular value in evaluating borderline or atypical cases in which other genodermatoses presenting with poikiloderma or other overlapping features such as poikiloderma with neutropenia, dyskeratosis congenita, Werner syndrome, and Fanconi anemia must also be considered. Additionally, the test should be offered to all juvenile osteosarcoma cases with poikilodermalike lesions. In these cases, genetic testing of the RECQL4 gene would allow for establishment of the correct diagnosis and thus accurate syndrome-specific surveillance.

Imaging Studies

In Rothmund-Thomson syndrome (poikiloderma congenitale), baseline skeletal radiographs of the long bones by age 5 years are recommended due to the high frequency of skeletal dysplasias, many of which may be clinically asymptomatic.[25]

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.



Medical Care

Persons with Rothmund-Thomson syndrome (poikiloderma congenitale) should apply sunscreens with UVA and UVB coverage regularly. Additionally, keratolytics and retinoids have been somewhat successful in treating the hyperkeratotic lesions.

Surgical Care

Telangiectases can be treated with pulsed-dye laser therapy.[26]


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.

A dermatologist may be consulted to monitor for the development of skin cancers.



Medication Summary

The goals of pharmacotherapy for Rothmund-Thomson syndrome (poikiloderma congenitale) are to reduce morbidity and to prevent complications.

Retinoid-like Agents

Class Summary

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

Isotretinoin (Amnesteem, Claravis, Myorisan, Sotrel)

Isotretinoin is a synthetic 13-cis isomer of the naturally occurring tretinoin (trans-retinoic acid). It is approved for use in severe recalcitrant nodular acne.

A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

Tretinoin topical (Atralin, Refissa, Renova, Avita, Retin-A)

Tretinoin inhibits microcomedo formation and eliminates lesions. It makes keratinocytes in sebaceous follicles less adherent and easier to remove. Tretinoin topical is available as 0.025%, 0.05%, and 0.1% creams and 0.01% and 0.025% gels.

Acitretin (Soriatane)

Acitretin is a metabolite of etretinate and related to both retinoic acid and retinol (vitamin A). Its mechanism of action is unknown. However, it is thought to exert therapeutic effect by modulating keratinocyte differentiation, keratinocyte hyperproliferation, and tissue infiltration by inflammatory cells. Acitretin is approved for the treatment of severe psoriasis.

Keratolytic Agents

Class Summary

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

Salicylic acid topical (Clean & Clear Advantage, Neutrogena)

By dissolving the intercellular cement substance, salicylic acid produces desquamation of the horny layer of skin, while not affecting the structure of viable epidermis.