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Orphanet Journal of Rare Diseases Jan 2010Rothmund-Thomson syndrome (RTS) is a genodermatosis presenting with a characteristic facial rash (poikiloderma) associated with short stature, sparse scalp hair, sparse... (Review)
Review
Rothmund-Thomson syndrome (RTS) is a genodermatosis presenting with a characteristic facial rash (poikiloderma) associated with short stature, sparse scalp hair, sparse or absent eyelashes and/or eyebrows, juvenile cataracts, skeletal abnormalities, radial ray defects, premature aging and a predisposition to cancer. The prevalence is unknown but around 300 cases have been reported in the literature so far. The diagnostic hallmark is facial erythema, which spreads to the extremities but spares the trunk, and which manifests itself within the first year and then develops into poikiloderma. Two clinical subforms of RTS have been defined: RTSI characterised by poikiloderma, ectodermal dysplasia and juvenile cataracts, and RTSII characterised by poikiloderma, congenital bone defects and an increased risk of osteosarcoma in childhood and skin cancer later in life. The skeletal abnormalities may be overt (frontal bossing, saddle nose and congenital radial ray defects), and/or subtle (visible only by radiographic analysis). Gastrointestinal, respiratory and haematological signs have been reported in a few patients. RTS is transmitted in an autosomal recessive manner and is genetically heterogeneous: RTSII is caused by homozygous or compound heterozygous mutations in the RECQL4 helicase gene (detected in 60-65% of RTS patients), whereas the aetiology in RTSI remains unknown. Diagnosis is based on clinical findings (primarily on the age of onset, spreading and appearance of the poikiloderma) and molecular analysis for RECQL4 mutations. Missense mutations are rare, while frameshift, nonsense mutations and splice-site mutations prevail. A fully informative test requires transcript analysis not to overlook intronic deletions causing missplicing. The diagnosis of RTS should be considered in all patients with osteosarcoma, particularly if associated with skin changes. The differential diagnosis should include other causes of childhood poikiloderma (including dyskeratosis congenita, Kindler syndrome and Poikiloderma with Neutropaenia), other rare genodermatoses with prominent telangiectasias (including Bloom syndrome, Werner syndrome and Ataxia-telangiectasia) and the allelic disorders, RAPADILINO syndrome and Baller-Gerold syndrome, which also share some clinical features. A few mutations recur in all three RECQL4 diseases. Genetic counselling should be provided for RTS patients and their families, together with a recommendation for cancer surveillance for all patients with RTSII. Patients should be managed by a multidisciplinary team and offered long term follow-up. Treatment includes the use of pulsed dye laser photocoagulation to improve the telangiectatic component of the rash, surgical removal of the cataracts and standard treatment for individuals who develop cancer. Although some clinical signs suggest precocious aging, life expectancy is not impaired in RTS patients if they do not develop cancer. Outcomes in patients with osteosarcoma are similar in RTS and non-RTS patients, with a five-year survival rate of 60-70%. The sensitivity of RTS cells to genotoxic agents exploiting cells with a known RECQL4 status is being elucidated and is aimed at optimizing the chemotherapeutic regimen for osteosarcoma.
Topics: Frameshift Mutation; Humans; RecQ Helicases; Rothmund-Thomson Syndrome
PubMed: 20113479
DOI: 10.1186/1750-1172-5-2 -
Dermatologic Clinics Jan 1995Rothmund-Thomson syndrome is a rare inherited disorder characterized by poikilodermatous skin changes that appear in infancy. The inheritance is autosomal recessive.... (Review)
Review
Rothmund-Thomson syndrome is a rare inherited disorder characterized by poikilodermatous skin changes that appear in infancy. The inheritance is autosomal recessive. Patients exhibit variable features including skeletal abnormalities, juvenile cataracts, and a higher-than-expected incidence of malignancy. This article describes aspects of the inheritance, the incidence of characteristic features, and the malignant potential of Rothmund-Thomson syndrome. Insight into its origin is provided through a review of the clinical signs and symptoms, the in vitro studies of endocrine function, and the reported DNA repair abnormalities.
Topics: Adult; Bone Neoplasms; Bone and Bones; Cataract; Child, Preschool; DNA Repair; Endocrine Glands; Female; Humans; Infant; Male; Osteosarcoma; Precancerous Conditions; Rothmund-Thomson Syndrome; Skin Neoplasms
PubMed: 7712640
DOI: No ID Found -
Nihon Ronen Igakkai Zasshi. Japanese... 2021
Topics: Humans; Rothmund-Thomson Syndrome
PubMed: 34483168
DOI: 10.3143/geriatrics.58.413 -
Ageing Research Reviews Jan 2017Rothmund-Thomson Syndrome (RTS) is a rare autosomal recessive disease which manifests several clinical features of accelerated aging. These findings include atrophic... (Review)
Review
Rothmund-Thomson Syndrome (RTS) is a rare autosomal recessive disease which manifests several clinical features of accelerated aging. These findings include atrophic skin and pigment changes, alopecia, osteopenia, cataracts, and an increased incidence of cancer for patients carrying RECQL4 germline mutations. Mutations in RECQL4 are responsible for the majority of cases of RTS. RECQL4 belongs to RECQ DNA helicase family which has been shown to participate in many aspects of DNA metabolism. In the past several years, accumulated evidence indicates that RECQL4 is important not only in cancer development but also in the aging process. In this review, based on recent research data, we summarize the common aging findings in RTS patients and propose possible mechanisms to explain the aging features in these patients.
Topics: Aging; Humans; Mutation; RecQ Helicases; Rothmund-Thomson Syndrome; Symptom Assessment
PubMed: 27287744
DOI: 10.1016/j.arr.2016.06.002 -
Pediatrics International : Official... Jan 2022Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma of the face, small stature, sparse scalp hair, juvenile...
BACKGROUND
Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma of the face, small stature, sparse scalp hair, juvenile cataract, radial aplasia, and predisposition to cancers. Due to the rarity of RTS, the situation of patients with RTS in Japan has not been elucidated.
METHODS
In 2010 and 2020, following the results of a primary questionnaire survey, a secondary questionnaire survey on RTS was conducted nationwide to investigate the number of RTS cases and their associated skin lesions, bone lesions, other clinical features, and quality of life in Japan.
RESULTS
In 2010 and 2020, 10 and eight patients with RTS were recruited, respectively. Skin lesions such as poikiloderma, erythema, pigmentation, and abnormal scalp hair were observed in almost all cases. Bone lesions were observed in four cases in the 2010 and 2020 surveys, respectively. Two cases had mutations in the RECQL4 gene in the 2020 survey.
CONCLUSIONS
Two nationwide surveys have shown the actual situation of patients with RTS in Japan. Cutaneous and bone manifestations are important for the diagnosis of RTS. However, many patients have no RECQL4 mutations. The novel causative gene of RTS should be further elucidated.
Topics: Humans; Japan; Mutation; Quality of Life; Rothmund-Thomson Syndrome; Surveys and Questionnaires
PubMed: 35616152
DOI: 10.1111/ped.15120 -
Journal of the American Academy of... Feb 1993Rothmund-Thomson syndrome is a rare genodermatosis that features a progressive, early-onset poikiloderma, a high incidence of juvenile cataracts, stunted growth, and a... (Review)
Review
Rothmund-Thomson syndrome is a rare genodermatosis that features a progressive, early-onset poikiloderma, a high incidence of juvenile cataracts, stunted growth, and a wide range of skeletal abnormalities. We report the seventh case of osteosarcoma in a patient with Rothmund-Thomson syndrome and review the previous reports describing this association.
Topics: Bone Neoplasms; Child; Femur; Humans; Male; Osteosarcoma; Rothmund-Thomson Syndrome
PubMed: 8436644
DOI: 10.1016/0190-9622(93)70040-z -
Boletin Medico Del Hospital Infantil de... 2022Rothmund-Thomson syndrome, also known as congenital poikiloderma, is a rare autosomal recessive genodermatosis with onset in early childhood that affects at a...
BACKGROUND
Rothmund-Thomson syndrome, also known as congenital poikiloderma, is a rare autosomal recessive genodermatosis with onset in early childhood that affects at a multisystem level.
CASE REPORTS
Case 1. A 4-year-old male patient, consanguineous parents, 26-year-old brother with a probable diagnosis of Rothmund-Thompson syndrome. He presented with adactyly of the right thumb, hypoplasia of the left thumb, delayed growth and psychomotor development. At 3 months, he presented rough, dry, sparse hair and erythematous lesions on the face, leaving hyperpigmented and hypopigmented spots with a reticulated pattern. We detected hypoacusis, skeletal alterations, narrow chin, short stature, severe malnutrition, and chronic and asymptomatic hypodontia. Genetic sequencing showed a mutation for the RECQL4 gene, for which a multidisciplinary follow-up was provided by the genetics, gastroenterology, nutrition, endocrinology, stomatology, audiology, orthopedics, rehabilitation, ophthalmology and oncology services. Case 2. A 2-year-old female patient presented facial erythema that spread to the arms and legs at 3 months; skin biopsy showed poikiloderma. She was evaluated by the endocrinology service and followed up for short stature and hypogonadism. A genetic study was not performed.
CONCLUSIONS
Rothmund-Thomson syndrome is characterized by atrophy. Only a few cases are reported in the literature. We present two cases of Rothmund-Thomson syndrome, emphasizing its clinical and dermatological characteristics.
Topics: Adult; Child; Child, Preschool; Female; Hospitals, Pediatric; Humans; Male; Mexico; Mutation; Rothmund-Thomson Syndrome
PubMed: 35086131
DOI: 10.24875/BMHIM.21000013 -
DNA Repair Mar 2010RECQ proteins are conserved DNA helicases in both prokaryotes and eukaryotes. The importance of the RECQ family helicases in human health is demonstrated by their roles... (Review)
Review
RECQ proteins are conserved DNA helicases in both prokaryotes and eukaryotes. The importance of the RECQ family helicases in human health is demonstrated by their roles as cancer suppressors that are vital for preserving genome integrity. Mutations in one of the RECQ family proteins, RECQ4, not only result in developmental abnormalities and cancer predispositions, but are also linked to premature aging. Therefore, defining the function and regulation of the RECQ4 protein is fundamental to our understanding of both the aging process and cancer pathogenesis. This review will summarize the clinical effect of RECQ4 in human health, and discuss the recent progress and debate in defining the complex molecular function of RECQ4 in DNA metabolism.
Topics: Animals; DNA; DNA Repair; DNA Replication; Humans; Protein Binding; RecQ Helicases; Rothmund-Thomson Syndrome
PubMed: 20096650
DOI: 10.1016/j.dnarep.2010.01.006 -
The British Journal of Dermatology Mar 1991
Topics: Adult; Female; Humans; Immune Tolerance; Leukemia, Myeloid; Rothmund-Thomson Syndrome
PubMed: 2018741
DOI: 10.1111/j.1365-2133.1991.tb00581.x -
Cancer Letters Jan 2006Rothmund-Thomson Syndrome (RTS) is a rare autosomal recessive genodermatosis with a heterogeneous clinical profile. Mutations in RECQL4, encoding a RecQ DNA helicase,... (Review)
Review
Rothmund-Thomson Syndrome (RTS) is a rare autosomal recessive genodermatosis with a heterogeneous clinical profile. Mutations in RECQL4, encoding a RecQ DNA helicase, are present in a large fraction, but not all clinically diagnosed patients, allowing to classify RTS among the RecQ helicase chromosomal instability defects including Bloom's and Werner's syndromes. Results of RECQL4 test coupled to the variable clinical presentation favored the splitting of RTS clinical phenotype into nosological entities under distinct genetic control. In parallel, lumping of the RECQL4 gene to two other diseases, RAPADILINO and Baller-Gerold has paved the way to unravel through allelic heterogeneity complex genotype-phenotype correlations. Recql4 knockout mice provided crucial insights into the comprehension of the functional role of RECQL4 helicase, which have been corroborated by the initial biochemical characterization of RECQL4 protein and its acting pathway and by studies on RECQL4 homologs in yeast and Xenopus. A role for RECQL4 in initiation of DNA replication and in sister chromatid cohesion has been proposed, which currently fits the pieces of evidence achieved by different approaches. Further work is needed to define the specific and shared functions of RECQL4 in relation to other RecQ helicases and to connect RECQL4 diseases to other genomic instability syndromes with birth defects and cancer predisposition.
Topics: Adenosine Triphosphatases; Animals; Chromosomal Instability; Chromosome Segregation; DNA Helicases; Genetic Predisposition to Disease; Humans; Mutation; RecQ Helicases; Rothmund-Thomson Syndrome
PubMed: 16271439
DOI: 10.1016/j.canlet.2005.07.042