The Experts below are selected from a list of 1269 Experts worldwide ranked by ideXlab platform
Lisa L. Wang - One of the best experts on this subject based on the ideXlab platform.
-
Rothmund-Thomson Syndrome
2016Co-Authors: Lisa L. Wang, Sharon E. PlonAbstract:Clinical characteristics Rothmund-Thomson Syndrome (RTS) is characterized by a rash that progresses to poikiloderma; sparse hair, eyelashes, and/or eyebrows; small size; skeletal and dental abnormalities; juvenile cataracts; and an increased risk for cancer, especially osteosarcoma. A variety of benign and malignant hematologic abnormalities have been reported in affected individuals. The rash of RTS typically develops between ages three and six months (occasionally as late as age two years) as erythema, swelling, and blistering on the face, subsequently spreading to the buttocks and extremities. The rash evolves over months to years into the chronic pattern of reticulated hypo- and hyperpigmentation, telangiectasias, and punctate atrophy (collectively known as poikiloderma) that persist throughout life. Hyperkeratotic lesions occur in approximately one third of individuals. Skeletal abnormalities can include radial ray defects, ulnar defects, absent or hypoplastic patella, and osteopenia. Diagnosis/testing The diagnosis of RTS is established by clinical findings (in particular, the characteristic rash) and/or the identification of biallelic pathogenic variants in ANAPC1 or RECQL4 on molecular genetic testing. Management Treatment of manifestations: Pulsed dye laser to the telangiectatic component of the rash for cosmetic management; surgical removal of cataracts; standard treatment for cancer and/or hematologic concerns. Surveillance: Annual general physical, dermatologic, and eye examination; monitoring of health and growth, skin for lesions with unusual color or texture, for cataracts. Prompt skeletal radiographic examination when clinical suspicion of osteosarcoma is present (bone pain, swelling or enlarging lesion on a limb); however, surveillance screening for osteosarcoma is not routinely recommended. Agents/circumstances to avoid: Excessive exposure to heat or sunlight; growth hormone for those with short stature with normal growth hormone levels. Genetic counseling RTS is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible if the ANAPC1 or RECQL4 pathogenic variants in the family are known.
-
Aging in Rothmund-Thomson Syndrome and related RECQL4 genetic disorders.
Ageing research reviews, 2016Co-Authors: Weidong Jin, Lisa L. WangAbstract: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.
-
Metatarsal osteosarcoma in Rothmund-Thomson Syndrome: a case report.
The Journal of bone and joint surgery. American volume, 2010Co-Authors: Debabrata Padhy, Vrisha Madhuri, Susanne Pulimood, Sumita Danda, Noel Walter, Lisa L. WangAbstract:Osteosarcoma is known to occur in association with a number of dysmorphic genetic Syndromes1. Rothmund-Thomson Syndrome is one such disorder, characterized by poikiloderma, small stature, sparse hair, skeletal defects, and an association with malignant lesions, particularly osteosarcoma. Thirty-six cases of osteosarcoma in patients with Rothmund-Thomson Syndrome have been described in the English-language literature, to our knowledge; none of the tumors in those patients originated in the metatarsals or metacarpals2-6. We describe a case of osteosarcoma of the metatarsal in an adolescent male patient with Rothmund-Thomson Syndrome. The patient and his father were informed that information concerning this case would be submitted for publication, and the father consented. A seventeen-year-old boy presented with a ten-month history of progressive swelling of and pain in the first ray of the right foot. He was the fourth child born to consanguineous parents. At the age of six months, he had development of facial erythema, which spread to the arms, legs, and buttocks, later evolving into a reddish-brown rash with hypopigmented lesions. The skin lesions were less prominent on the trunk. He had delayed developmental milestones and was a slow learner. There was no family history of cancer, dermatological problems, or learning disabilities. Examination revealed a height of 145 cm and a weight of 30 kg (both below the third percentile for age). Cutaneous examination showed reticulated, pigmented macules with atrophy and telangiectases predominantly on the cheeks, elbows, knees, thighs, buttocks, and dorsal parts of the hands and feet (Fig. 1). The patient had punctate keratoderma of the hands and feet and hyperkeratosis of the palms and soles. The left fourth fingernail was rudimentary, and the patient had sparse scalp hair, eyebrows, and eyelashes. His mental and verbal abilities were those of a nine-year-old child. Examination of the eyes …
-
intron size constraint as a mutational mechanism in Rothmund Thomson Syndrome
American Journal of Human Genetics, 2002Co-Authors: Lisa L. Wang, Kim C. Worley, Anu Gannavarapu, Murali Chintagumpala, Moise L. Levy, Sharon E. PlonAbstract:Rothmund-Thomson Syndrome (RTS) is an autosomal recessive disorder caused by deleterious mutations in the RECQL4 gene on chromosome 8. The RECQL4 gene structure is unusual because it contains many small introns <100 bp. We describe a proband with RTS who has a novel 11-bp intronic deletion, and we show that this mutation results in a 66-bp intron too small for proper splicing. Constraint on intron size may represent a general mutational mechanism, since human-genome analysis reveals that ∼15% of genes have introns <100 bp and are therefore susceptible to size constraint. Thus, monitoring of intron size may allow detection of mutations missed by exon-by-exon approaches.
-
Intron-Size Constraint as a Mutational Mechanism in Rothmund-Thomson Syndrome
American journal of human genetics, 2002Co-Authors: Lisa L. Wang, Kim C. Worley, Anu Gannavarapu, Murali Chintagumpala, Moise L. Levy, Sharon E. PlonAbstract:Rothmund-Thomson Syndrome (RTS) is an autosomal recessive disorder caused by deleterious mutations in the RECQL4 gene on chromosome 8. The RECQL4 gene structure is unusual because it contains many small introns
Sharon E. Plon - One of the best experts on this subject based on the ideXlab platform.
-
Rothmund-Thomson Syndrome
2016Co-Authors: Lisa L. Wang, Sharon E. PlonAbstract:Clinical characteristics Rothmund-Thomson Syndrome (RTS) is characterized by a rash that progresses to poikiloderma; sparse hair, eyelashes, and/or eyebrows; small size; skeletal and dental abnormalities; juvenile cataracts; and an increased risk for cancer, especially osteosarcoma. A variety of benign and malignant hematologic abnormalities have been reported in affected individuals. The rash of RTS typically develops between ages three and six months (occasionally as late as age two years) as erythema, swelling, and blistering on the face, subsequently spreading to the buttocks and extremities. The rash evolves over months to years into the chronic pattern of reticulated hypo- and hyperpigmentation, telangiectasias, and punctate atrophy (collectively known as poikiloderma) that persist throughout life. Hyperkeratotic lesions occur in approximately one third of individuals. Skeletal abnormalities can include radial ray defects, ulnar defects, absent or hypoplastic patella, and osteopenia. Diagnosis/testing The diagnosis of RTS is established by clinical findings (in particular, the characteristic rash) and/or the identification of biallelic pathogenic variants in ANAPC1 or RECQL4 on molecular genetic testing. Management Treatment of manifestations: Pulsed dye laser to the telangiectatic component of the rash for cosmetic management; surgical removal of cataracts; standard treatment for cancer and/or hematologic concerns. Surveillance: Annual general physical, dermatologic, and eye examination; monitoring of health and growth, skin for lesions with unusual color or texture, for cataracts. Prompt skeletal radiographic examination when clinical suspicion of osteosarcoma is present (bone pain, swelling or enlarging lesion on a limb); however, surveillance screening for osteosarcoma is not routinely recommended. Agents/circumstances to avoid: Excessive exposure to heat or sunlight; growth hormone for those with short stature with normal growth hormone levels. Genetic counseling RTS is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible if the ANAPC1 or RECQL4 pathogenic variants in the family are known.
-
intron size constraint as a mutational mechanism in Rothmund Thomson Syndrome
American Journal of Human Genetics, 2002Co-Authors: Lisa L. Wang, Kim C. Worley, Anu Gannavarapu, Murali Chintagumpala, Moise L. Levy, Sharon E. PlonAbstract:Rothmund-Thomson Syndrome (RTS) is an autosomal recessive disorder caused by deleterious mutations in the RECQL4 gene on chromosome 8. The RECQL4 gene structure is unusual because it contains many small introns <100 bp. We describe a proband with RTS who has a novel 11-bp intronic deletion, and we show that this mutation results in a 66-bp intron too small for proper splicing. Constraint on intron size may represent a general mutational mechanism, since human-genome analysis reveals that ∼15% of genes have introns <100 bp and are therefore susceptible to size constraint. Thus, monitoring of intron size may allow detection of mutations missed by exon-by-exon approaches.
-
Intron-Size Constraint as a Mutational Mechanism in Rothmund-Thomson Syndrome
American journal of human genetics, 2002Co-Authors: Lisa L. Wang, Kim C. Worley, Anu Gannavarapu, Murali Chintagumpala, Moise L. Levy, Sharon E. PlonAbstract:Rothmund-Thomson Syndrome (RTS) is an autosomal recessive disorder caused by deleterious mutations in the RECQL4 gene on chromosome 8. The RECQL4 gene structure is unusual because it contains many small introns
Vincent J.b. Robinson - One of the best experts on this subject based on the ideXlab platform.
-
Osteogenic sarcoma associated with the Rothmund-Thomson Syndrome
Clinical Nuclear Medicine, 1998Co-Authors: Katarzyna J. Macura, George J. Burke, Vincent J.b. RobinsonAbstract:The Rothmund-Thomson Syndrome (RTS), also called poikiloderma congenitale, is a rare autosomal recessive disorder characterized by photosensitivity, poikiloderma of the face and extremities, juvenile cataracts, skeletal abnormalities, and a higher incidence of malignancy. Presented is the case of a 6-year-old boy with RTS who developed an osteogenic sarcoma of the tibia. A bone scan showed bilateral radius agenesis and a hot bone lesion in the proximal tibia metaphysis. An incisional bone biopsy led to a diagnosis of osteogenic sarcoma. There is an association between RTS and osteosarcoma, and there should be a high index of suspicion when patients with RTS develop bony pain.
A. O'meara - One of the best experts on this subject based on the ideXlab platform.
-
Osteogenic sarcoma and Rothmund Thomson Syndrome.
Journal of cancer research and clinical oncology, 1992Co-Authors: M. Varughese, Patrick J. Leavey, P. Smith, R. Sneath, F. Breatnach, A. O'mearaAbstract:Rothmund Thomson Syndrome (RTS) is a rare autosomal recessive disorder characterised by poikiloderma, dermal atrophy, dystrophic nails, short stature and hypogonadism. An increased incidence of malignancy has been reported in patients with this Syndrome secondary, it is postulated, to DNA repair defects. We report the occurrence of an osteogenic sarcoma in an 11-year-old Irish girl with RTS. Although fibroblast cultures demonstrated enhanced radiosensitivity, there was no undue toxicity associated with treatment, which included methotrexate, cisplatinum and Adriamycin. Following conservative surgery, she is currently off treatment and disease-free 2 years from diagnosis.
Katarzyna J. Macura - One of the best experts on this subject based on the ideXlab platform.
-
Osteogenic sarcoma associated with the Rothmund-Thomson Syndrome
Clinical Nuclear Medicine, 1998Co-Authors: Katarzyna J. Macura, George J. Burke, Vincent J.b. RobinsonAbstract:The Rothmund-Thomson Syndrome (RTS), also called poikiloderma congenitale, is a rare autosomal recessive disorder characterized by photosensitivity, poikiloderma of the face and extremities, juvenile cataracts, skeletal abnormalities, and a higher incidence of malignancy. Presented is the case of a 6-year-old boy with RTS who developed an osteogenic sarcoma of the tibia. A bone scan showed bilateral radius agenesis and a hot bone lesion in the proximal tibia metaphysis. An incisional bone biopsy led to a diagnosis of osteogenic sarcoma. There is an association between RTS and osteosarcoma, and there should be a high index of suspicion when patients with RTS develop bony pain.
