Analysis of RECQL4 gene variant in a child with Rothmund-Thomson syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with Rothmund-Thomson syndrome (RTS).@*METHODS@#The child has featured poikeloderma, short stature, cataract, sparse hair and skeletal malformation. Peripheral blood samples of the child and her family members were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing.@*RESULTS@#The child was found to harbor compound heterozygous variants of the RECQL4 gene, namely c.1048_1049delAG and c.2886-1G>A, among which c.2886-1G>A was unreported previously. According to the ACMG guidelines, the c.1048_1049delAG was predicted to be pathogenic (PVS1+PM3_Strong+PM2), while the c.2886-1G>A was predicted to be likely pathogenic (PVS1+PM2).@*CONCLUSION@#The compound heterozygous variants of the RECQL4 gene probably underlay the pathogenesis of RTS in this patient. Above finding has enriched the mutational spectrum of the RECQL4 gene.

Síndrome de Kindler: comunicación de casos / Kindler syndrome: a report of a case

El síndrome de Kindler es un cuadro autosómico recesivo, caracterizado por fotosensibilidad, envejecimiento prematuro, poiquilodermia y propensión al desarrollo de cáncer de piel. Se presenta una paciente de 16 años, procedente del sur de Honduras, hija de padres no consanguíneos, sin antecedentes familiares relevantes y con historia de dermatosis diseminada que afecta la cabeza, el tronco y las extremidades superiores e inferiores. Esta se caracterizaba por la presencia de placas atróficas con telangiectasias, que se exacerbaban ante la exposición al sol, con formación de ampollas, especialmente en el dorso de las manos, y por cicatrices atróficas similares al papel de cigarrillo.

Kindler syndrome is an autosomal recessive syndrome characterized by photosensitivity, premature aging, poikiloderma and propensity to develop skin cancer.A sixteen years old patient from southern Honduras, daughter of non consanguineous parents with no family history, is presented. In her first year she developed a dermatosis disseminated to the head, trunk and upper and lower extremities, characterized by atrophic plaques with telangiectasias exacerbated up to blistering when exposed to the sun, especially on the back of hands, with atrophic scars similar to paper cigarette.

Rothmund-Thomson syndrome and ocular surface findings: case reports and review of the literature / Síndrome de Rothmund-Thomson e achados da superfície ocular: casos clínicos e revisão da literatura

ABSTRACT 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.

RESUMO A síndrome de Rothmund-Thomson (SRT) é uma dermatose rara com cerca de 300 casos reportados. Os autores descrevem dois irmãos com síndrome de Rothmund-Thomson e doença inflamatória conjuntival com encurtamento do fundo de saco e simbléfaro, assim como doença palpebral com escassez de cilíos. Ambos os casos demonstram achados da superfície ocular diferentes dos habitualmente descritos.

Síndrome de Rothmund / Rothmund syndrome

RESUMO A síndrome de Rothmund (RTS) é uma rara genodermatose, de herança autossômica recessiva. Sua incidência é desconhecida, com aproximadamente 300 casos descritos na literatura. A síndrome é determinada por eritema facial (poiquilodermia), seu marco diagnóstico, além de alterações esqueléticas, alopecia, catarata juvenil e predisposição a osteossarcoma. Neste relato, descrevemos uma paciente com esta síndrome, que foi referida ao serviço de oftalmologia por baixa visão e hiperemia ocular.

ABSTRACT Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis. While its incidence is unknown, approximately 300 cases have been reported in the literature. The syndrome typically presents with a characteristic facial rash (poikiloderma), its diagnostic hallmark, and heterogeneous clinical features including congenital skeletal abnormalities, sparse hair distribution, juvenile cataracts, and a predisposition to osteosarcoma. This is a report describing a patient diagnosed with RTS referred to us because of low vision and red eyes.

Rothmund Thomson syndrome

Rothmund Thomson Syndrome is a rare autosomal recessive syndrome caused by homozygous or compound heterozygous mutations in [RECQL4] gene. It was first described in 1868 by a German ophthalmologist [Rothmund1] and later in 1936 by an English dermatologist [Thomson2] who reported another three similar patients but the oponym Rothmund Thomson Syndrome [RTS] was named by Taylor3 in 1957

Hereditary Sclerosing Poikiloderma

Hereditary sclerosing poikiloderma (HSP) is a very rare disease. The clinical features are principally widespread poikiloderma and linear hyperkeratotic and sclerotic bands. We report an 18-yr-old male who presented reticular hyperpigmented lesions on the trunk and extremities since 2-yr-old. Also, linear sclerosing bands appeared on both antecubital and popliteal fossae after yr. Histopathologic finding showed dense sclerotic collagen fibers with telangiectasia in the upper dermis and fragmentations of damaged elastic fibers in the elastic stain, consistent with HSP. We report the first Korean case of HSP.

Rothmund-Thomson syndrome in a Filipino child: Report of a rare case

Rothmund-Thomson syndrome (RTS) is a rare, autosomal recessive disorder characterized by early onset of progressive poikiloderma, cutaneous and extracutaneous findings including sparse hair, juvenile cataracts, short stature, skeletal defects, hypogonadism, dystrophic teeth and nails.This is a case of a 4-year-old boy who developed at 2 months of age, reticulated erythematous macules and patches over predominantly sun-exposed areas such as the malar areas, ears, neck, extensor surfaces of the forearms and legs. This later on progressed into poikilodermatous lesions associated with sparse scalp hair, eyebrows, eyelashes and short stature. This is a report on the first documented Filipino patient diagnosed with RTS.

Terapia fotodinâmica no tratamento da poiquilodermia de Civatte: avaliação clínica e histopatológica / Photodynamic therapy in the treatment of poikiloderma of Civatte: a clinical and histopathologic evaluation

A Poiquilodermia de Civatte (PC) é uma alteração dermatológica caracterizada por atrofia, pigmentação macular ou reticulada e telangiectasias na face, pescoço e tórax anterior. Várias tentativas de tratamentos não foram bem sucedidas por se mostrarem ineficazes e/ou com efeitos colaterais indesejáveis. Estudos clínicos mostram bons resultados clínicos no tratamento da PC com luz intensa pulsada (LIP). A terapia fotodinâmica (TFD) é uma modalidade terapêutica que envolve a administração tópica de um composto fotossensibilizante seguido de irradiação seletiva da lesão com luz visível. O propósito deste trabalho consiste na avaliação clínica e histopatológica da pele com PC, no tórax anterior, em 12 pacientes do sexo feminino, antes e após o tratamento com a TFD. Foram realizadas 3 sessões de tratamento com intervalos de 30 dias entre as sessões. A TFD foi realizada com a utilização prévia de cloridrato de aminolevulinato de metila 16% em creme (Metivix) 1h e 30min (oclusivo) antes da aplicação da LIP (Lime light). A avaliação clínica mostrou melhora em 84,6% no componente vascular, 80,8% no componente melanodérmico, 82,9% na textura, 77,1% nas rítides e 58,3% na flacidez de pele. Na histopatologia notou-se após o tratamento aumento estatisticamente significativo da espessura epidérmica, diminuição estatisticamente significativa do pigmento melânico e da área dos vasos marcados pelo fator VIII. Não houve nenhum efeito colateral permanente, mostrando que a TFD-MAL é uma nova opção terapêutica segura e eficaz para o tratamento da PC no tórax anterior.

Poikiloderma of Civatte (PC) is the dermatological modification characterized by atrophy, macular or reticulate pigmentation and telangiectasias on the face, neck and anterior thorax. Several treatment attempts were unsuccessful, revealing to be ineffective and/or causing adverse effects. Clinical studies indicate good clinical results in the treatment of poikiloderma of Civatte with intense pulsed light (IPL). Photodynamic Therapy (PDT) is a therapeutic modality that involves the topical administration of a photosensitizing compound, followed by a selective irradiation of the lesion with visible light. The objective of this study consisted in the clinical and histopathologic evaluations of the skin with poikiloderma of Civatte (PC) on the anterior thorax of 12 female patients, before and after being treated with photodynamic therapy (PDT). Three treatment sessions were given at 30-day intervals. Photodynamic therapy was performed with methyl aminolevulinate hydrochloride 16% (Metivix) cream applied 1h and 30min under occlusion prior to LIP (Lime light) exposure. The clinical evaluation indicated an 84.6% improvement of vascular component, 80.8% of melanodermic component, 82.9% of texture, 77.1% of wrinkles and 58.3% of skin laxity. In the histopathology, a statistically significant increase of epidermal thickness was observed after the treatment, as well as a statistically significant reduction in the number of melanin pigment and of blood vessels area marked for Factor VIII. There were no permanent side effects, showing that the PDT-MAL is a new, safe and effective technic for treating PC on the anterior thorax.

Osteosarcoma: Biologic Markers in Its Treatment

Osteosarcoma is a primary malignant bone tumor that accounts for 5% of childhood cancers. Despite the use of chemotherapy, long-term survival has reached a plateau, and this figure has not changed for almost 20 years. Therefore, there is a need for understanding of the basic biology and pathogenesis of osteosarcoma in order to develop more therapeutic strategies and ultimately improve survival. This article reviews current state of knowledge about several aspects of osteosarcoma biology with regard to host genetic predispositions, cytogenetics and molecular markers. Genetic conditions with a predisposition to osteosarcoma include hereditary retinoblastoma, Li-Fraumeni syndrome, Rothmund-Thomson syndrome and Werner syndrome. Although most of osteosarcomas are sporadic, these syndromes may provide important clues to the pathogenesis of sporadic osteosarcomas. A multitude of cytogenetic abnormalities have been detected, but no specific abnormalities that can serve as markers of osteosarcoma have been found. Areas of molecular aberrations include tumor suppressor pathway (RB and p53), oncogenes (Her-2), telomere maintenance, angiogenesis (VEGF), chemokines (CXCR4), cytoskeletons (Ezrin), matrix metalloproteinases and adhesion molecules (CD44). Understanding the contributions of the different cytogenetic and molecular aberrations will aid in discovering predictors of outcome and in devising therapies for osteosarcoma.

A case of Rothmund-Thomson syndrome / 소아과

Rothmund-Thomson syndrome (RTS), is a rare autosomal recessive disorder, characterized by:skin photosensitivity, poikiloderma, sparse hair, sparse eyebrows/lashes, short stature, skeletal abnormalities, cataracts, and an increased risk of malignancy. Skeletal abnormalities include:dysplasia, absent or malformed bones, such as absent radii, osteopenia, and delayed bone formation. RTS is thought to result from chromosomal instability, and children with RTS are at risk of cancer. Reported cancers in children with RTS include:basal cell carcinoma, squamous cell carcinoma of the skin and osteosarcoma of bone. We report an 11 year-old boy, who presented to our institution with poikilodermatous skin change with telangiectasia and hyperpigmentation, absence of radius and thumb, and the development of osteosarcoma of the left tibia. The patient is now receiving supportive care and is receiving maintenance chemotherapy after surgery for osteosarcoma.

Kindler syndrome.

Kindler syndrome is a rare autosomal recessive disorder associated with skin fragility. It is characterized by blistering in infancy, photosensitivity and progressive poikiloderma. The syndrome involves the skin and mucous membrane with radiological changes. The genetic defect has been identified on the short arm of chromosome 20. This report describes an 18-year-old patient with classical features like blistering and photosensitivity in childhood and the subsequent development of poikiloderma. The differential diagnosis of Kindler syndrome includes diseases like Bloom syndrome, Cockayne syndrome, dyskeratosis congenita, epidermolysis bullosa, Rothmund-Thomson syndrome and xeroderma pigmentosum. Our patient had classical cutaneous features of Kindler syndrome with phimosis as a complication.

Poiquilodermia acroqueratótica hereditaria (Weary): enfermedad inmunológica. Ubicación nosológica en una clasificación de las poiquilodermis ampollares hereditarias. Presentación de un caso con estudio inmunológico y ultraestructural / Acrokeratotic hereditary poikiloderma

Se realiza una revisión bibliográfica de casos de poiquilodermia Acroqueratótica Hereditaria o enfermedad de Weary (EW). Hemos concluido que dicha denominación pareciera ser usada en cuatro diferentes cuadros dermatológicos: 1) Enfermedad de Weary Acroqueratótica Hereditaria con herencia familiar autosómica dominante (EW-d); 2) Enfermedad de Weary, con herencia familiar autosómica recesiva y algunos rasgos clínicos de una EW-d asociada a manifestaciones de fotosensibilidad de un síndrome de Kindler; 3) Síndrome de Kindler-Weary (SK-W) con lesiones clínicas de un síndrome de Kindler (poliquilodermia con ampollas traumáticas y atrofia cutánea progresiva) e histopatológicas con manifestaciones liquenoides y presencia de "cuerpos citoides" de una EW-d y 4) Síndrome de Weary-Kindler con manifestaciones de una Poiquilodermia Esclerosante Hereditaria de Weary (HSP), asociada también a manifestaciones ampollares de un SK-r (WE-KS-r). Nosotros relatamos un nuevo caso clínico e histopatológico de una EW-d con presencia de "cuerpos citoides", como expresión de una reacción inmunológica mediada por células, demostrable por inmunohistoquímica. En el diagnóstico diferencial se destaca la distinta patogenia del SK que presenta una malformación displásica genética de la membrana basal electrónica (láminas lúcida y densa) y del tejido conectivo papilar dérmico con desaparición de las fibras elásticas. Nuestra revisión bibliográfica demostró que la EW-d y el SK-r representan dos "formas polares" patogénicas: una predominantemente inmunológica y la segunda malformativa displásica genética, en un amplio espectro de Poiquilodermias Ampollares Hereditarias (HAP), vinculadas con otras cuatro "formas subpolares": EW-r, SK-r, WE-KS-r y SK-d. Estas conclusiones están basadas en el análisis patogénico, clínico, histopatológico, inmunohistoquímico y ultraestructural de componentes del HAP

A Case of Rothmund-Thomson Syndrome with Pure Red Cell Aplasia, Autoimmune Hemolytic Anemia and Chronic Respiratory Infection / 소아과

Rothmund-Thomson syndrome(RTS), or poikiloderma congenita, is a rare, multisystem disorder. It is inherited genetically as an autosomal recessive trait, occurring predominantly in females(1.4 : 1). The RTS is comprised of poikiloderma, short stature, sparse hair, juvenile cataracts, skeletal defects, dystrophic teeth and nails, photosensitivity, and hypogonadism. We report a case of RTS who died of bleeding from esophageal varices, pulmonary hemorrhage and septic shock at 25 years of age and had suffered from various diseases such as transient pure red cell aplasia, autoimmune hemolytic anemia, chronic maxillary sinusitis, bronchiectasis, secondary hemochromatosis, and liver cirrhosis in addition to poikiloderma, alopecia, and sexual infantalism which are typical of RTS.

Late-onset polymyositis in a case of poikilodermatomyositis.

A case of poikiloderma developed polymyositis ten years after the onset of skin changes. This rare case of poikilodermatomyositis, hitherto not reported from Asian continent, is documented.

A Case of Rothmund-Thomson Syndrome / 대한피부과학회지

Rothmund-Thomson syndrome is a rare autosomal recessive genodermatosis, which is characterized by poikiloderma and photosensitivity with variable features including alopecia, sparse hair, short stature, skeletal abnormalities, juvenile cataracts, and an increased risk of developing skin and bone malignancies. A 19-year-old man presented with poikilodermatous skin change on the whole body since three months old, and accompanied by photosensitivity, alopecia, and brachydactyly. As far as we know, this is the first case report of Rothmund-Thomson syndrome in Korea.

Sindrome poiquilodermia congenita / Sindrome poiquilodermia congenita

El síndrome de poiquilodermia congénita, denominado también síndrome de Tothmund Thomson o poiquilodermia atrófica, es una genodermatosís rara que presenta una gama variada de manifestaciones clínicas, siendo las características más comunes: Estatura baja, eritema irregular que progresa a poiquilodermia, altraciones esqueléticas, cabellos escasos y catarata juvenil. Describimos el caso de un adolescente masculino de 13 años de edad que fue atendido en el Servicio de Pediatría del "Hospital Obrero N§ 3" - CNS, por presentar el mencionado síndrome.

Síndrome de Rothmund-Thomson poiquilodermia congénita / Rothmund-Thomson syndrome (poikilodermia congenita)

El síndrome de Rothmund-Thomson es una rara genodermatosis autosómica recesiva, descrita por primera vez en 1868. Se caracteriza por cambios poiquilodérmicos (atrofia, telangiectasias, despigmentación), cataratas juveniles y anormalidades esqueléticas. Presentamos dos pacientes portadores de éste síndrome, justificando ésta publicación en la baja frecuencia de la entidad, destacando las calcificaciones cutáneas como una asociación inusual en uno de los casos