Rothmund-Thomson Syndrome

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Classification according to ICD-10
Q82.8 Other specified congenital skin malformations
ICD-10 online (WHO version 2019)

The Rothmund-Thomson syndrome (RTS) is a autosomal - recessive inherited skin disease ( genodermatosis ).

Symptoms and Characterization

A) A four year old girl with poikiloderma on her cheeks. B) A 21 year old male with poikiloderma and alopecia . C) poikiloderma. D) Poikiloderma that does not affect the trunk. E) Poikiloderma and valgization . F) Aplasia of the thumb . G) bone deformation on X-ray.

The disease is characterized by a characteristic rash on the face ( poikiloderma ) in the affected patients . Poikilodermia is the main symptom of Rothmund-Thomson syndrome and is used to differentiate it from RAPADILINO syndrome . For Poikiloderma come short stature , sparse hair of the head , sparse or absent lashes and / or eyebrows , juvenile cataract , malformations of the skeleton , acromicria radial clubhand ( engl. Radial ray defect ), premature aging , as well as a predisposition for cancer .

A distinction is made between two clinical sub-forms of Rothmund-Thomson syndrome. Type 1 (RTS1) is characterized by juvenile cataracts, poikiloderma, and ectodermal dysplasia, while type 2 (RTS2) is characterized by poikiloderma, congenital bone deformities, and an increased risk of osteosarcomas in adolescence and skin cancer later in life. Some of the skeletal malformations are clearly visible, such as prominent forehead, saddle nose and radial club hand, but some are only visible radiologically.

Epidemiology

Rothmund-Thomson syndrome is a very rare disease. No reliable data are available on the prevalence . By 2010, about 300 patients are listed in the medical literature.

According to the autosomal recessive inheritance, most cases of RTS are not isolated, but occur in families, predominantly in blood related families or small communities. The carrier frequency of the mutation is unknown.

Both sexes can be affected by the disease. The gender distribution of RTS is - due to the small number of cases - not yet established. There have been reports of equal distribution, female dominance of 1.4: 1, and male dominance of 2: 1. RTS cases have been described in all races . A founder effect has not yet been discovered in any population , even if certain mutations may exist within a defined population.

genetics

Rothmund-Thomson syndrome is inherited in an autosomal recessive way and is genetically heterogeneous. RTS2 is homozygous or compound heterozygous mutations in RECQL4 - gene which codes for a helicase encoded caused. Missense mutations are much rarer than frameshift , nonsense and splice site mutations. Defects in the RECQL4 gene are the cause of the disease in around 60 to 65% of all RTS patients (RTS2).

The etiology of RTS1, however, is still unknown.

diagnosis

Due to the unspecific symptoms of RTS, there are no clinical criteria or a rating table ( score ) to categorize the diagnosis of RTS into clear , probable or possible . The clinical diagnosis is currently based on the time of onset of the disease, its progression and the occurrence of poikiloderma. According to Wang and Plon, the diagnosis of RTS can probably be made if the rash is atypical and two of the following criteria are met: thin hair on the head, eyebrows and eyelashes; Short stature; congenital bone deformations such as B. Radial aplasia (including those that can only be detected by imaging ); abnormal teeth and nails; Hyperkeratosis ; Cataract and cancer.

Especially in patients with osteosarcoma and skin changes, the possibility of Rothmund-Thomson syndrome should be considered as a cause of the disease.

In molecular diagnostics, the diagnosis of patients with RTS2 - around two thirds of all RTS patients - can be confirmed by DNA analysis of the RECQL4 gene. It should be noted that Baller-Gerold syndrome and RAPADILINO syndrome are also associated with mutations of RECQL4 and sometimes have very similar symptoms.

therapy

Treatment of Rothmund-Thomson syndrome is largely symptomatic and, because of the complexity of the disease, interdisciplinary between dermatologists, ophthalmologists, orthopedists, surgeons and oncologists. Stem cell transplants have so far only been carried out on two patients (as of 2010). In one case an allogeneic bone marrow transplant, in another one with cord blood stem cells .

forecast

The life expectancy of patients, even if premature aging is visible, is largely normal if the cancers are identified and treated in good time. In the case of osteosarcoma in RTS patients, the 5-year survival rate - as in osteosarcoma patients without RTS - is in the range of 60 to 70%.

Initial description

August von Rothmund

The Rothmund-Thomson syndrome was first described in 1868 by the German ophthalmologist August von Rothmund . The British doctor Matthew Sydney Thomson (1894–1969) published a treatise in 1936 on two cases of Poikiloderma Congenitale (hereditary poikiloderma), a disease identical to that described by Rothmund and which later got the names of the two doctors.

further reading

Individual evidence

  1. ↑ Orphanet : RAPADILINO Syndrome. Retrieved January 9, 2011
  2. ↑ a b c d e f g h i j k L. Larizza, G. Roversi, L. Volpi: Rothmund-Thomson syndrome. In: Orphanet Journal of Rare Diseases Volume 5, 2010, p. 2, ISSN  1750-1172 . doi: 10.1186 / 1750-1172-5-2 . PMID 20113479 . PMC 2826297 (free full text). (Review). ( Open access )
  3. ↑ EM Vennos, M. Collins, WD James: Rothmund-Thomson syndrome: review of the world literature. In: Journal of the American Academy of Dermatology Volume 27, Number 5 Pt 1, November 1992, pp. 750-762, ISSN  0190-9622 . PMID 1430398 . (Review).
  4. ↑ EM Vennos, WD James: Rothmund-Thomson syndrome. In: Dermatologic Clinics Volume 13, Number 1, January 1995, pp. 143-150, ISSN  0733-8635 . PMID 7712640 . (Review).
  5. ↑ a b A. Rothmund: About cataracts in connection with a peculiar skin degeneration. In: Archives for Ophtalmology Volume 14, 1868, pp. 159-182. doi : 10.1007 / BF02720945
  6. ↑ a b M. S. Thomson: Poikiloderma Congenitale: Two Cases for Diagnosis. In: Proceedings of the Royal Society of Medicine Volume 29, Number 5, March 1936, pp. 453-455, ISSN  0035-9157 . PMID 19990626 . PMC 2076117 (free full text).
  7. ^ S. Kitao, A. Shimamoto, M. Goto, RW Miller, WA Smithson, NM Lindor, Y. Furuichi: Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. In: Nature genetics Volume 22, Number 1, May 1999, pp. 82-84, ISSN  1061-4036 . doi : 10.1038 / 8788 . PMID 10319867 .
  8. ^ S. Hsu: Rothmund-Thomson Syndrome. In: e-medicine from October 13, 2009
  9. ^ LL Wang and SE Plon: Rothmund-Thomson Syndrome. RA Pagon et al. (Editors): GeneReviews Seattle, 1993-1999, PMID 20301415 .
  10. ↑ LA Pujol, RP Erickson, RA Heidenreich, C. Cunniff: Variable presentation of Rothmund-Thomson syndrome. In: American journal of medical genetics Volume 95, Number 3, November 2000, pp. 204-207, ISSN  0148-7299 . PMID 11102924 .
  11. ↑ M. Debeljak, A. Zver, J. Jazbec: A patient with Baller-Gerold syndrome and midline NK / T lymphoma. In: American journal of medical genetics. Part A Volume 149A, Number 4, February 2009, pp. 755-759, ISSN  1552-4833 . doi: 10.1002 / ajmg.a.32736 . PMID 19291770 .
  12. ↑ Y. Sznajer, HA Siitonen, G. Roversi, C. Dangoisse, M. Scaillon, F. Ziereisen, S. Tenoutasse, M. Kestilä, L. Larizza: Atypical Rothmund-Thomson syndrome in a patient with compound heterozygous mutations in RECQL4 gene and phenotypic features in RECQL4 syndromes. In: European Journal of Pediatrics Volume 167, Number 2, February 2008, pp. 175-181, ISSN  1432-1076 . doi: 10.1007 / s00431-007-0447-6 . PMID 17372760 .
  13. ^ R. Kellermayer, HA Siitonen, K. Hadzsiev, M. Kestilä, G. Kosztolányi: A patient with Rothmund-Thomson syndrome and all features of RAPADILINO. In: Archives of Dermatology Volume 141, Number 5, May 2005, pp. 617-620, ISSN  0003-987X . doi: 10.1001 / archderm.141.5.617 . PMID 15897384 .
  14. ↑ C. Rizzari, D. Bacchiocchi, A. Rovelli, A. Biondi, A. Cantu'-Rajnoldi, C. Uderzo, G. Masera: Myelodysplastic syndrome in a child with Rothmund-Thomson syndrome: a case report. In: Journal of pediatric hematology / oncology: official journal of the American Society of Pediatric Hematology / Oncology Volume 18, Number 1, February 1996, pp. 96-97, ISSN  1077-4114 . PMID 8556381 .
  15. ↑ MA Broom, LL Wang, SK Otta, AP Knutsen, E. Siegfried, JR Batanian, ME Kelly, M. Shah: Successful umbilical cord blood stem cell transplantation in a patient with Rothmund-Thomson syndrome and combined immunodeficiency. In: Clinical genetics Volume 69, Number 4, April 2006, pp. 337-343, ISSN  0009-9163 . doi : 10.1111 / j.1399-0004.2006.00592.x . PMID 16630167 .
  16. ↑ MJ Hicks, JR Roth, CA Kozinetz, LL Wang: Clinicopathologic features of osteosarcoma in patients with Rothmund-Thomson syndrome. In: Journal of clinical oncology  : official journal of the American Society of Clinical Oncology Volume 25, Number 4, February 2007, pp. 370-375, ISSN  1527-7755 . doi : 10.1200 / JCO.2006.08.4558 . PMID 17264332 .

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