ABSTRACT
Background: Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder characterized by cutaneous and ocular photosensitivity and an increased risk of developing cutaneous neoplasms. Progressive neurological abnormalities develop in a quarter of XP patients. Aim: To study the clinical profile and perform a mutation analysis in Indian patients with xeroderma pigmentosum. Methods: Ten families with 13 patients with XP were referred to our clinic over 2 years. The genes XPA, XPB and XPC were sequentially analyzed till a pathogenic mutation was identified. Results: Homozygous mutations in the XPA gene were seen in patients with moderate to severe mental retardation (6/10 families) but not in those without neurological features. Two unrelated families with a common family name and belonging to the same community from Maharashtra were found to have an identical mutation in the XPA gene, namely c.335_338delTTATinsCATAAGAAA (p.F112SfsX2). Testing of the XPC gene in two families with four affected children led to the identification of the novel mutations c.1243C>T or p.R415X and c.1677C>A or p.Y559X. In two families, mutations could not be identified in XPA, XPB and XPC genes. Limitation: The sample size is small. Conclusion: Indian patients who have neurological abnormalities associated with XP should be screened for mutations in the XPA gene.
Subject(s)
Adolescent , Adult , Child , Family/epidemiology , Female , Founder Effect , Humans , India/epidemiology , Male , Mutation/analysis , Mutation/genetics , Mutation, Missense/genetics , Neurologic Manifestations , Xeroderma Pigmentosum/epidemiology , Xeroderma Pigmentosum/genetics , Xeroderma Pigmentosum/pathology , Xeroderma Pigmentosum Group A Protein/geneticsABSTRACT
The De Sanctis-Cacchione Syndrome is the rarest and most severe kind of xeroderma pigmentosum, characterized by microcephaly, hypogonadism, neurological disorders, mental and growth retardation, with very few cases published. The clinical findings compatible with De Sanctis-Cacchione Syndrome and the therapeutic approach used to treat a one year and nine months old child, with previous diagnosis of xeroderma pigmentosum, are reported.
A síndrome de de Sanctis-Cacchione é a forma mais rara e grave do xeroderma pigmentoso e é caracterizada por microcefalia, hipogonadismo, alterações neurológicas e retardo mental e de crescimento, com poucos casos publicados. Relatam-se os achados clínicos compatíveis com essa síndrome e a terapêutica instituída em uma lactente de um ano e nove meses, com diagnóstico prévio de xeroderma pigmentoso.
Subject(s)
Female , Humans , Infant , Dwarfism/pathology , Hypogonadism/pathology , Intellectual Disability/pathology , Rare Diseases/pathology , Skin Neoplasms/pathology , Xeroderma Pigmentosum/pathology , Dwarfism/therapy , Hypogonadism/therapy , Intellectual Disability/therapy , Prognosis , Rare Diseases/therapy , Skin Neoplasms/therapy , Skin/pathology , Xeroderma Pigmentosum/therapyABSTRACT
El xeroderma pigmentoso (XP) es una rara enfermedad, autosómica recesiva, causada por un defecto en la reparación del ADN. Se manifiesta en la niñez temprana. Los pacientes conXP tienen una extrema fotosensibilidad, lo que conduce a quemaduras solares, cambios pigmentarios y una elevada incidencia de tumores malignos de piel. Una minoría de pacientes presenta anomalías neurológicas progresivas. El diagnóstico es clínico y puede ser confirmado con estudios genéticos. El tratamiento consiste en una rigurosa fotoprotección y la extirpación precoz de lesiones precancerosas. Presentamos el caso de un niño de 2 años de edad con compromiso cutáneo y ocular, sinalteraciones neurológicas...
Subject(s)
Humans , DNA Repair/genetics , Xeroderma Pigmentosum/diagnosis , Xeroderma Pigmentosum/pathology , Skin DiseasesABSTRACT
Xeroderma pigmentosum [XP] is a rare autosomal recessive disease characterised by photosensitivity, pigmentary changes, premature skin ageing and development of various cutaneous and internal malignancies at an early age due to defective nucleotide excision repair following exposure to ultraviolet radiations. Conjunctival malignant melanoma has a very rare association with XP. In this regard, we report a case of a 14-year-old boy suffering from XP with malignant melanoma of conjunctiva
Subject(s)
Humans , Male , Adolescent , Xeroderma Pigmentosum/pathology , Conjunctival Neoplasms , Xeroderma Pigmentosum/complicationsABSTRACT
Xeroderma pigmentosa is a rare inherited autosomal recessive disease with the inability to repair DNA damage caused by UV light. Recognized in the late 1800 by Maritz Kaposi it has been reported world wide and in all races with an over prevalence of 1-4 per million population. Kunwar et al. Those affected are extremely sensitive to the UV portion of the light and have a 2000-fold increased risk of skin cancer in the sun exposed skin. Basal cell carcinoma is the most commonly associated carcinoma followed by Squamous cell carcinoma and Melanoma. The pigmentation on the face and the rest of the body can be horribly disfiguring. The recurring cancer occurring on the face and repeated surgical treatment for the ulcerations have important social and psychological implications not encountered with other cancers. We report two cases of BCC and melanoma. The first case is of BCC of the face in a teenaged girl coexisting with xeroderma pigmentosa. The second case presented with melanoma of the scalp in a 10 year old female child. The details of these cases are presented and the management.
Subject(s)
Adolescent , Carcinoma, Basal Cell/pathology , Child , Female , Humans , Melanoma/pathology , Skin Neoplasms/pathology , Xeroderma Pigmentosum/pathologyABSTRACT
To evaluate the feasibility, tolerance/toxicity and therapeutic efficacy of 5-fluorouracil[5-FU]by topical application and systemic use, in facial carcinoma associated with XP. This is a prospective study of 10 patients with a median age of 22.9 years and a sex ratio of 4. Tumour lesions were facial mainly in the jugal and temporal region [36%]. Chemotherapy indication was discussed in multidisciplinary committee, the topical 5-fluorouracil was applied locally twice a day, whereas the systemic treatment consisted of FUFOL protocol [every 4 weeks a combinaison of a short perfusion of 340mg/m 2 5-FU and preceded by an infusion of 20mg/m 2 of folic acid, day I to 5]; or C-FU protocol, combining continuous infusion of 5-FU [Ig/m 2] 5 days associated with cisplatin [100mg/m 2,dayl] every 3 weeks. The median topical treatment duration was of 12 months in 10 patients. We noted a full tumoral regression in 10% of cases. Concerning systemic treatment, the median number of FUFOL cycles was 4 [2 to 6] and we observed a complete response in 6 patients [60%], partial in 2 cases [20%]. Treatment was well tolerated in most cases except for the cutaneous irritation on 5-FU application zone and a 4 grade cisplatin otoxicity. Systemic or topical chemotherapy represents an interesting palliative option for facial carcinoma associated with XP, avoiding reiterated surgery and its cosmetic consequences
Subject(s)
Humans , Male , Female , Xeroderma Pigmentosum/pathology , Face , Fluorouracil , Skin Neoplasms , Neoplasm Metastasis , Prospective Studies , Administration, TopicalABSTRACT
Os autores apresentam um caso clínico de xeroderma pigmentoso, doença muito rara, de caráter autossômico recessivo, multissistêmica, degenerativa e progressiva. É feita uma revisao da literatura e analisados os aspectos epidemiológicos e as diferentes formas clínicas. Discutem-se as formas de tratamento e os resultados histopatológicos. O caso clínico é descrito e documentado; o plano terapêutico adotado foi de ressecçao de toda a pele facial, para retirada de áreas afetadas por lesoes tumorais e de pele com alto potencial de malignizaçao. Estas regioes foram auto-enxertadas com pele de média espessura, respeitando-se as unidades estéticas da face; a área doadora escolhida foi a regiao femoral por tratar-se de pele pouco exposta aos raios ultra-violeta. O material foi enviado a estudo histopatológico. O resultado histopatológico confirmou o diagnóstico clínico. É apresentada a evoluçao do paciente após seis meses da intervençao cirúrgica. Enfatiza-se neste trabalho a importância da orientaçao dada aos pacientes portadores desta doença, especificamente a nao exposiçao à luz solar. Por fim, discute-se a abordagem multidisciplinar a que estes pacientes devem se submeter, a fim de prevenir e tratar precocemente as lesoes tumorais, obtendo-se assim um melhor prognóstico.
Subject(s)
Humans , Male , Adolescent , Xeroderma Pigmentosum , Xeroderma Pigmentosum/pathology , Xeroderma Pigmentosum/surgeryABSTRACT
Se examinó la respuesta citogética que presentan las células normales y las de pacientes con xeroderma pigmentosum ante la radiación ultravioleta. Los resultados mostraron un incremento significativo de brechas y rupturas cromatídicas, así como de la depresión de la división celular en las células afectadas en comparación con las normales. Estos datos confirman la fragilidad cromosómica de células de pacientes con xerocerma pigmentosum ante agentes ambientales, lo que se encuentra en el contexto de una secuencia que se inicia en deficiencias en la repación de DNA y continúa con la presencia de mutaciones y el desarrollo de cáncer
Subject(s)
Humans , Adolescent , Adult , Male , Female , Chromosome Aberrations , In Vitro Techniques , Ultraviolet Rays/adverse effects , Xeroderma Pigmentosum/pathology , Fibroblasts/radiation effects , DNA Repair/radiation effectsABSTRACT
Los autores presentan un caso de Pseudosarcoma de Kaposi localizado en dos dedos de la mano izquierdo de un paciente con insuficiencia renal, que tenía una fístula arteriovenosa en la muñeca izquierda para la hemodiálisis