Understanding Rothmund-Thomson Syndrome (RTS): Causes, Symptoms, and Care

Medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: October 2026

Rothmund-Thomson syndrome (RTS) is an extremely rare genetic disorder that affects multiple organ systems, including the skin, bones, and eyes. Characterized by a distinctive facial rash called poikiloderma and an increased risk of certain cancers, RTS requires lifelong clinical surveillance. While there is no cure, proactive management of symptoms, such as cataract surgery and strict sun protection, allows many individuals to lead typical lifespans, and they usually have typical intelligence.

Quick Answer: What is Rothmund-Thomson syndrome (RTS)?

Rothmund-Thomson syndrome (RTS) is a rare inherited condition caused by mutations in genes like RECQL4. [1] [4] It usually appears in infancy as a red, patchy rash on the cheeks that later spreads to the limbs, along with sparse hair, dental problems, small stature and bone abnormalities. People with RTS face higher bone and skin cancer risk and need regular monitoring. [1]

What the research says

• Carriers of one RECQL4 variant did not show a significantly higher cancer rate. In the largest international RTS registry, 3 of 123 RECQL4 heterozygous family members (2.4%) had cancer, compared with an age-adjusted population estimate of 5.6% (P = 0.2), which helps guide counseling for parents and siblings of people with RTS (Martin-Giacalone et al., Cancer Genetics, 2022) [2].

• Osteosarcoma in RTS appears earlier but behaves like typical osteosarcoma. Among 12 patients with RTS and osteosarcoma, the median age at diagnosis was 10 years, most tumors were in the long bones, 8 patients were alive and disease free and 4 died of cancer, and 5 needed chemotherapy dose changes, most often because of mouth sores from doxorubicin (Hicks et al., Journal of Clinical Oncology, 2007) [3].

• The condition varies from person to person. A report of three Chinese patients with biallelic RECQL4 variants found that all had poikiloderma, short stature and sparse hair, eyelashes and eyebrows, but only one developed osteosarcoma (at age 13) and one also had intellectual disability and speech delay, showing that features differ between individuals (Zhang et al., The Journal of Dermatology, 2021) [4].

What genetic changes cause Rothmund-Thomson syndrome?

Rothmund-Thomson syndrome is an autosomal recessive genetic disorder [2] [4], meaning a child must inherit a mutated gene from both parents to develop the condition. Researchers have identified mutations in the ANAPC1 and RECQL4 genes as primary causes, although some cases occur without these specific markers for reasons that are not yet fully understood. [1] [4]

Because it is an inherited condition, families with a history of RTS may benefit from genetic counseling. If both parents are carriers of a mutation, there is a 25% chance with each pregnancy that the child will be born with the syndrome. [1] Despite its systemic effects, RTS typically does not impact intelligence [1], and the overall prognosis is favorable provided that secondary complications, such as cancer, are detected and treated early.

Affected System	Clinical Manifestations	Long-Term Considerations
Dermatological	Poikiloderma (rash), blisters, calluses.	Higher risk of basal and squamous cell carcinoma.
Skeletal	Small, fused, absent, or thin bones; small nose.	Increased fracture risk; orthopedic surgery needs.
Dental	Missing, misshapen, or late-growing teeth.	Higher risk of cavities; restorative dentistry.
Ocular	Cataracts, beginning around ages 3 to 7.	May need vision-correcting cataract surgery.
Hematologic	Anemia; low white blood cell counts.	Ongoing monitoring of blood health.

How does Rothmund-Thomson syndrome progress, and what are its symptoms?

The first signs of Rothmund-Thomson syndrome usually appear within the first year of life. [1] The most recognizable symptom is a skin rash known as poikiloderma, which typically begins on the cheeks between three and six months of age before spreading to the buttocks and extremities. This rash involves a combination of skin thinning, redness, and patchy pigmentation changes.

In addition to skin changes, infants with RTS often experience feeding difficulties, including persistent vomiting and diarrhea. [1] As the child grows, physical development may be affected, leading to a smaller overall stature and distinct facial features such as a protruding jaw. [1] Sparse hair growth, including the absence of eyelashes and eyebrows, is also a common clinical marker. [1]

Figure 1: Illustration of the early clinical markers of RTS, focusing on poikiloderma development and skeletal malformations.

How is Rothmund-Thomson syndrome diagnosed and monitored?

Diagnosis is primarily achieved through a thorough clinical examination of physical symptoms. Healthcare providers may use a skin biopsy to confirm the cellular changes associated with poikiloderma or order genetic testing to identify mutations in the RECQL4 or ANAPC1 genes. [1] However, a negative genetic test does not rule out RTS if clinical signs are present.

Lifelong surveillance is the cornerstone of RTS management. Because of the elevated risk of osteosarcoma (bone cancer) and various skin cancers, patients must undergo regular screenings. [1] Parents should be vigilant for new skin lesions, persistent bone pain, or unexplained swelling or bumps in the limbs [1], as these may be early indicators of malignancy.

Figure 2: Infographic detailing the multidisciplinary diagnostic approach and the critical areas for ongoing medical monitoring.

How is Rothmund-Thomson syndrome managed with multidisciplinary care?

Rothmund-Thomson syndrome has no cure for its underlying genetic mutation, but its symptoms are highly manageable. A multidisciplinary team, including dermatologists, ophthalmologists, orthopedists, and oncologists [1], works together to address the specific needs of each patient. Key interventions often include cataract surgery to preserve vision and orthopedic procedures to correct bone abnormalities. [1]

Preventive care is equally vital. Individuals with RTS must practice strict sun protection [1], including the use of high-SPF sunscreen and protective clothing, to minimize the risk of skin cancer. Regular dental checkups are also necessary to manage the misshapen teeth and increased cavity risk associated with the syndrome. [1]

Figure 3: Overview of the clinical pathway for RTS, highlighting the transition from infant diagnosis to adult surveillance and preventive care.

How can people live with Rothmund-Thomson syndrome (RTS), and what are next steps?

If someone in your family has RTS, genetic counseling can help you understand your chance of having a child with the condition. [1] If your child has RTS, tell your healthcare provider right away about any new skin lesions, especially changes in color or texture, and about swelling, bumps, or pain in the arms or legs. [1]

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Frequently Asked Questions

How rare is Rothmund-Thomson syndrome?

Rothmund-Thomson syndrome is extremely rare, with only about 300 cases documented by experts worldwide.

Is RTS always inherited from parents?

Yes, it is a genetic disorder. If both parents carry the mutation, there is a 1 in 4 chance their child will have RTS.

What is poikiloderma?

Poikiloderma is a specific type of skin rash involving redness, pigmentation changes, and thinning of the skin, which is a hallmark of RTS.

At what age do symptoms usually start?

Symptoms typically begin in the first year of life, with the characteristic rash often appearing between 3 and 6 months of age.

Does RTS affect intelligence?

Individuals with Rothmund-Thomson syndrome usually have typical intelligence and cognitive development, although features vary between individuals.

Can people with RTS have children?

RTS can affect fertility; for example, women with the condition may experience abnormal menstruation, which can impact reproductive health.

What are the most common cancers associated with RTS?

The highest risks are for osteosarcoma (bone cancer) and skin cancers like basal cell and squamous cell carcinoma. Lymphatic leukemia and lymphoma have also been reported.

Can cataracts in RTS be treated?

Yes, cataracts, which often develop between ages 3 and 7, can be treated with surgery to improve vision.

Is there a cure for Rothmund-Thomson syndrome?

There is currently no cure for the genetic mutation itself, but the symptoms can be effectively managed through medical and surgical care.

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References

1. Cleveland Clinic. Rothmund-Thomson Syndrome (RTS). Cleveland Clinic. September 10, 2022. https://my.clevelandclinic.org/health/diseases/24154-rothmund-thomson-syndrome-rts

2. Martin-Giacalone BA, Rideau TT, Scheurer ME, et al. Cancer risk among RECQL4 heterozygotes. Cancer Genetics. 2022;262-263:107-110. PMID 35219053. https://doi.org/10.1016/j.cancergen.2022.02.001

3. Hicks MJ, Roth JR, Kozinetz CA, et al. Clinicopathologic features of osteosarcoma in patients with Rothmund-Thomson syndrome. Journal of Clinical Oncology. 2007;25(4):370-375. PMID 17264332. https://doi.org/10.1200/JCO.2006.08.4558

4. Zhang Y, Qin W, Wang H, et al. Novel pathogenic variants in the RECQL4 gene causing Rothmund-Thomson syndrome in three Chinese patients. The Journal of Dermatology. 2021;48(10):1511-1517. PMID 34155702. https://doi.org/10.1111/1346-8138.16015

Medical disclaimer

The information provided in this article is for educational purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.