{{Short description|Rare autosomal recessive skin condition}} {{Infobox medical condition (new) | name = Rothmund–Thomson syndrome | synonyms = '''Poikiloderma atrophicans with cataract''' or '''Poikiloderma congenitale'''<ref name=omim/><ref name="Andrews">{{cite book |author1=James, William |author2=Berger, Timothy |author3=Elston, Dirk |year=2005 |title=Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.) |publisher=Saunders |isbn=978-0-7216-2921-6 |page=576}}</ref> | image = Rothmund-Thomson syndrome.jpg | caption = Panel showing some clinical features of the RTS syndrome. A) Chronic phase of cheek poikiloderma (4-year-old girl). B) Poikiloderma with alopecia (21-year-old boy). C) Poikiloderma. D) Poikiloderma sparing the trunk (courtesy of Professor M. Paradisi, Rome). E) Photo distributed poikiloderma and valgism of the knees. F) Thumb aplasia (patient B). G) Bone defect seen by X-Rays: cystic-like destructive lesion of the humerus (distal epiphysis) without apparent solution of continuity of the cortical bone (patient E). | pronounce = | field = | symptoms = | complications = | onset = | duration = | types = | causes = | risks = | diagnosis = | differential = | prevention = | treatment = | medication = | prognosis = | frequency = | deaths = }} '''Rothmund–Thomson syndrome''' ('''RTS''') is a rare autosomal recessive<ref name=rtsar>{{Cite journal | last1 = Larizza | first1 = L. | last2 = Roversi | first2 = G. | last3 = Volpi | first3 = L. | title = Rothmund-Thomson syndrome | journal = Orphanet Journal of Rare Diseases | volume = 5 | pages = 2 | date=Jan 2010 | pmid = 20113479 | pmc = 2826297| type = Free full text | doi = 10.1186/1750-1172-5-2 | doi-access = free }}</ref><ref>{{cite journal |vauthors=Raza N, Malik QU, Hussain Z |title=Rothmund-Thomson syndrome: more than just a cosmetic concern |journal=J Coll Physicians Surg Pak |volume=17 |issue=7 |pages=423–424 |year=2007 |pmid=17686357 }}</ref> skin condition.
There have been several reported cases associated with osteosarcoma. A hereditary basis, mutations in the DNA helicase ''RECQL4'' gene, causing problems during initiation of DNA replication has been implicated in the syndrome.<ref name=omim>{{OMIM|268400}}</ref><ref name=req/><ref>{{cite journal |vauthors=Hicks MJ, Roth JR, Kozinetz CA, Wang LL |title=Clinicopathologic features of osteosarcoma in patients with Rothmund-Thomson syndrome |journal=J. Clin. Oncol. |volume=25 |issue=4 |pages=370–5 |year=2007 |pmid=17264332 |doi=10.1200/JCO.2006.08.4558 |doi-access=free }}</ref><ref name="pmid15960976">{{cite journal |vauthors=Sangrithi MN, Bernal JA, Madine M, Philpott A, Lee J, Dunphy WG, Venkitaraman AR | title = Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome | journal = Cell | volume = 121 | issue = 6 | pages = 887–98 |date=Jun 2005 | pmid = 15960976 | doi = 10.1016/j.cell.2005.05.015 | s2cid = 15064074 | doi-access = free }}</ref>
==Signs and symptoms== * Sun-sensitive rash with prominent poikiloderma and telangiectasias * Juvenile cataracts * Saddle nose * Congenital bone defects, including short stature and radial ray anomalies such as absent thumbs * Hair growth problems (absent eyelashes, eyebrows and/or hair) * Hypogonadism has not been well documented * Hypodontia * Calcium problems (not documented in journals) * Ear problems (not documented in journals but identified by patients in support groups) * Produces osteosarcoma<ref>{{cite journal |vauthors=Wang LL, Levy ML, Lewis RA, etal |title=Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients |journal=Am. J. Med. Genet. |volume=102 |issue=1 |pages=11–17 |year=2001 |pmid=11471165 |doi=10.1002/1096-8628(20010722)102:1<11::AID-AJMG1413>3.0.CO;2-A}}</ref>
The skin is normal at birth. Between 3 and 6 months of age, the affected carrier develops poikiloderma on the cheeks. This characteristic "rash" that all RTS carriers have can develop on the arms, legs and buttocks. "Poikiloderma consists of areas of increased and decreased pigmentation, prominent blood vessels, and thinning of the skin."<ref>Understanding RTS pamphlet, RTS Team: Lisa L. Wang (Oncologist), Moise L. Levy (dermatologist), Richard A. Lewis (Ophthalmologist), Sharon E. Plon (Geneticist)</ref>
===Accelerated aging===
In humans, individuals with RTS, and carrying the ''RECQL4'' germline mutation, can have several clinical features of accelerated aging. These features include atrophic skin and pigment changes, alopecia, osteopenia, cataracts and an increased incidence of cancer.<ref name="pmid27287744">{{cite journal |vauthors=Lu L, Jin W, Wang LL |title=Aging in Rothmund-Thomson syndrome and related RECQL4 genetic disorders |journal=Ageing Res. Rev. |volume=33 |pages=30–35 |year=2017 |pmid=27287744 |doi=10.1016/j.arr.2016.06.002 |s2cid=28321025 }}</ref> Also in mice, ''RECQL4'' mutants show features of accelerated aging.<ref name="pmid24832598">{{cite journal |vauthors=Lu H, Fang EF, Sykora P, Kulikowicz T, Zhang Y, Becker KG, Croteau DL, Bohr VA |title=Senescence induced by RECQL4 dysfunction contributes to Rothmund-Thomson syndrome features in mice |journal=Cell Death Dis |volume=5 |issue= 5|pages=e1226 |year=2014 |pmid=24832598 |pmc=4047874 |doi=10.1038/cddis.2014.168 }}</ref>
== Causes == thumb|right|Rothmund–Thomson syndrome has an autosomal recessive pattern of inheritance. RTS is caused by a mutation of the ''RECQL4'' gene, located at chromosome 8q24.3.<ref name=req>{{Cite journal|vauthors=Larizza L, Magnani I, Roversi G | title = Rothmund–Thomson syndrome and RECQL4 defect: Splitting and lumping| journal = Cancer Letters| volume = 232| issue = 1| pages = 107–120| date = January 2006| pmid = 16271439| doi = 10.1016/j.canlet.2005.07.042}}</ref><ref>{{OMIM|603780}}</ref> The disorder is inherited in an autosomal recessive manner.<ref name=rtsar/> This means the defective gene responsible for the disorder is located on an autosome (chromosome 8 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.{{citation needed|date=September 2020}}
===DNA repair===
RECQL4 has a crucial role in DNA end resection that is the initial step required for homologous recombination (HR)-dependent double-strand break repair.<ref name="pmid27320928">{{cite journal |vauthors=Lu H, Shamanna RA, Keijzers G, Anand R, Rasmussen LJ, Cejka P, Croteau DL, Bohr VA |title=RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks |journal=Cell Rep |volume=16 |issue=1 |pages=161–73 |year=2016 |pmid=27320928 |pmc=5576896 |doi=10.1016/j.celrep.2016.05.079 }}</ref> When RECQL4 is depleted, HR-mediated repair and 5' end resection are severely reduced ''in vivo''. RECQL4 also appears to be necessary for other forms of DNA repair including non-homologous end joining, nucleotide excision repair and base excision repair.<ref name="pmid27287744" /> The association of deficient RECQL4-mediated DNA repair with accelerated aging is consistent with the DNA damage theory of aging.{{cn|date=November 2020}} == History == The condition was originally described by August von Rothmund (1830–1906) in 1868.<ref name="LuJin2016">{{cite journal|last1=Lu|first1=Linchao|last2=Jin|first2=Weidong|last3=Wang|first3=Lisa L.|title=Aging in Rothmund-Thomson syndrome and related RECQL4 genetic disorders|journal=Ageing Research Reviews|year=2016|issn=1568-1637|doi=10.1016/j.arr.2016.06.002|pmid=27287744|volume=33|pages=30–35|s2cid=28321025}}</ref> Matthew Sydney Thomson (1894–1969) published further descriptions in 1936.<ref>{{Cite journal | last1 = Thomson | first1 = MS. | title = Poikiloderma Congenitale: Two Cases for Diagnosis. | journal = Proc R Soc Med | volume = 29 | issue = 5 | pages = 453–5 |date=Mar 1936 | pmid = 19990626 | pmc=2076117}} </ref>
== See also == * Poikiloderma vasculare atrophicans * List of cutaneous conditions * List of radiographic findings associated with cutaneous conditions
==References== {{reflist}}
== External links == * [https://www.ncbi.nlm.nih.gov/books/NBK1237/ GeneReviews/NCBI/NIH/UW entry on Rothmund-Thomson Syndrome] * {{RareDiseases|4392|Poikiloderma of Rothmund-Thomson}} {{Medical resources | DiseasesDB = 29891 | ICD10 = {{ICD10|Q|82|8}} (ILDS Q82.852) | ICD9 = {{ICD9|757.33}} | OMIM = 268400 | MedlinePlus = | eMedicineSubj = derm | eMedicineTopic = 379 | MeshID = D011038 | GeneReviewsName=Rothmund-Thomson Syndrome | GeneReviewsNBK=NBK1237 | Orphanet=2909 }}
{{Congenital malformations and deformations of integument}} {{DNA repair-deficiency disorder}} {{Progeroid syndromes}}
{{DEFAULTSORT:Rothmund-Thomson syndrome}} Category:Autosomal recessive disorders Category:DNA replication and repair-deficiency disorders Category:Genodermatoses Category:Rare diseases Category:Syndromes affecting the skin Category:Progeroid syndromes Category:Syndromes affecting stature Category:Syndromes affecting the eye Category:Diseases named after discoverers