Review

Authors: Juliane Schierbeck, Tine Vestergaard, Anette Bygum...

Skin cancer has become the most common type of cancer worldwide as a result of environmental exposure and medical treatments. A small group of patients are genetically predisposed to skin cancer and this article is intended as a diagnostic tool when encountering patients with multiple skin cancer lesions. The disorders are described with clinical characteristics, genetics and management. The most common syndromes associated with basal cell carcinoma are: Gorlin-Goltz syndrome, Rombo syndrome, and Bazex-Dupré-Christol syndrome. Multiple squamous cell carcinomas can be related to: xeroderma pigmentosum, Ferguson-Smith, Muir-Torre syndrome, Mibelli-type porokeratosis, keratitis-ichthyosis-deafness syndrome, Rothmund-Thomson syndrome, Bloom syndrome, and epidermodysplasia verruciformis. Malignant melanoma can be inherited, as in familial atypical multiple mole melanoma syndrome.

Topics: Adolescent; Adult; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Humans; Male; Melanoma; Middle Aged; Mutation; Neoplastic Syndromes, Hereditary; Phenotype; Risk Assessment; Risk Factors; Skin; Skin Neoplasms; Treatment Outcome; Young Adult

PubMed: 30653245
DOI: 10.2340/00015555-3123

Review

Authors: Lidia Larizza, Gaia Roversi, Ludovica Volpi...

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

Review

Authors: Davi Jardim Martins, Ricardo Di Lazzaro Filho, Debora Romeo Bertola...

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by a range of clinical symptoms, including poikiloderma, juvenile cataracts, short stature, sparse hair, eyebrows/eyelashes, nail dysplasia, and skeletal abnormalities. While classically associated with mutations in the gene, which encodes a DNA helicase involved in DNA replication and repair, three additional genes have been recently identified in RTS: , encoding a subunit of the APC/C complex; which encodes a nuclease/helicase involved in DNA repair; and , encoding a poorly characterized protein implicated in excitatory synapse formation and splicing. Here, we review the clinical spectrum of RTS patients, analyze the genetic basis of the disease, and discuss molecular functions of the affected genes, drawing some novel genotype-phenotype correlations and proposing avenues for future studies into this enigmatic disorder.

PubMed: 38021400
DOI: 10.3389/fragi.2023.1296409

Authors: Sujaya Manavi, Vikram K Mahajan

PubMed: 25396146
DOI: 10.4103/2229-5178.142533

Authors:

Topics: Humans; Rothmund-Thomson Syndrome

PubMed: 34483168
DOI: 10.3143/geriatrics.58.413

Review

Authors: J T Chinmayee, G R Meghana, R K Prathiba...

A 24-year-old male patient presented to us with diminution of vision in both eyes with watering and photophobia for the past 8 years. General physical examination showed short stature and poikiloderma. Ocular findings include photophobia with reflex tearing, dry eye, cicatricial ectropion, symblepharon approaching pupillary area of cornea, and multiple superficial punctuate erosions on the cornea. Both eyelids showed scanty meibomian glands on infrared meibography. The rest of the anterior and posterior segment was normal. The patient was treated with topical lubricants which reduced photophobia and corneal erosions. He then underwent symblepharon release with buccal mucosal grafting, which improved ectropion. Patient improved symptomatically with reduction of photophobia and improvement in vision as well.

Topics: Diagnostic Techniques, Ophthalmological; Dry Eye Syndromes; Eyelid Diseases; Humans; Lubricant Eye Drops; Male; Meibomian Glands; Mouth Mucosa; Ophthalmologic Surgical Procedures; Rothmund-Thomson Syndrome; Young Adult

PubMed: 29044077
DOI: 10.4103/ijo.IJO_89_17

Review

Authors: Ana Filipa Miranda, Maria Daniela Rivera-Monge, Charles Costa Farias...

Rothmund-Thomson syndrome (RTS) is a rare dermatosis with about 300 cases reported to date. The authors describe two siblings with RTS and inflammatory conjunctival disease featuring fornix shortening and symblepharon as well as palpebral disease with sparse eyelashes. These cases demonstrate RTS ocular surface findings different to those usually described.

Topics: Adult; Conjunctiva; Conjunctivitis; Eyelashes; Eyelid Diseases; Female; Humans; Male; Rothmund-Thomson Syndrome; Tissue Adhesions

PubMed: 27463631
DOI: 10.5935/0004-2749.20160053