Incidence of DNA repair deficiency disorders in western Europe: Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy.

Xeroderma pigmentosa (XP) is a condition inherited as an autosomal recessive trait and is characterized by photosensitivity, pigmentary changes, premature skin ageing and malignant tumour development resulting from the defect in DNA repair. The management of complications of XP, especially orofacial tumours entails an enormous surgical challenge to the clinicians. We present five cases of XP.

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Xeroderma pigmentosum: a review and case series

Disseminated squamous cell carcinoma (SCC) of the skin is exceedingly rare in children. SCC occurs after immunodeficiency from immunosuppression in organ transplant recipients or patients with HIV infection or leukaemia, but has not been reported in primary immunodeficiencies other than epidermodysplasia verruciformis. Interferon γ receptor 2 (IFNγR2) deficiency is an exceedingly rare primary immunodeficiency, conferring almost selective predisposition to mycobacterial diseases. A disseminated, cutaneous SCC is described that occurred in a patient homozygous for a novel frameshift deletion at positions 949 and 950 (949delTG) in the IFNGR2 gene. The patient first presented at 1 year of age with disseminated Mycobacterium avium infection, with later infections of atypical mycobacteria ( Mycobacterium fortuitum and Mycobacterium porcium ). At 17 years of age, the patient developed multifocal SCC lesions on the face and both hands. Histopathological examination revealed well differentiated SCC. Despite local tumour excision, multiple lesions occurred and a large SCC on the right arm required amputation. The patient died at 20 years of age of disseminated SCC. Inherited disorders of IFNγ mediated immunity may predispose patients to SCC.

https://jmg.bmj.com/content/jmedgenet/early/2010/06/28/jmg.2009.072108.full.pdf

Multiple cutaneous squamous cell carcinomas in a patient with interferon γ receptor 2 (IFNγR2) deficiency

Xeroderma Pigmentosum: A Retrospective Case Series in Zimbabwe

Summary

Background Xeroderma pigmentosum type C (XP-C) is a rare, autosomal, recessive condition characterized by the association of various clinical manifestations mostly involving the skin and eyes.



Objectives  To evaluate the clinical manifestations in a homogeneous, genetically characterized cohort of patients with XP-C.



Methods  All patients with XP-C, which was confirmed genetically or by unscheduled DNA synthesis, from the registry of our department and from the French association of patients ‘Les Enfants de la Lune’ were contacted. During a planned consultation, clinical information was collected using a standardized case-record form.



Results  In total, 31 patients were seen. The mean age at diagnosis was 2·95 years; skin symptoms started at a mean age of 1·49 years. Among the patients, 52% had relatively short stature, with a height-for-weight z-score below −1 SD; 62% showed pyramidal syndrome and 45% had photophobia and/or conjunctivitis. Four patients had several pyogenic granulomas. Twenty-four patients (77%) had skin cancer. The mean age of onset of the first skin cancer was 4·76 years (range 2–14·5 years). Basal-cell carcinoma was the most frequent cancer. Melanomas were rare and mostly desmoplastic. Multinodular thyroid was the most frequent internal tumour.



Conclusions  Our data highlight several new aspects of XP-C. Patients with XP-C are at risk of developing pyogenic granulomas, desmoplastic melanomas and multinodular thyroid. Involvement of the central nervous system is frequent, but its mechanism remains unclear. The relatively short stature of the patients needs further investigation in order to be explained. XP-C is not only a cancer-prone disorder but is also a polysystemic disorder.

Unexpected extradermatological findings in 31 patients with xeroderma pigmentosum type C

Xeroderma pigmentosum (XP) is a rare autosomal recessive inherited disorder caused by a defect in the normal repair of DNA of various cutaneous cell types damaged by exposure to ultraviolet radiation We present our 7-year experience with 36 XP patients who either visited the Department of Dermatology or were seen in the medical camps arranged in remote areas for patients' welfare, from 1995 to 2001 For ease of discussion we classified all cases into the following subgroups on clinical grounds only: mild, those with light brown freckles on the face alone; moderate, those with dark brown freckles with burning on the face, neck, ears, chest, hands and photophobia but without other associated obvious cutaneous and ocular changes; severe, those with extensive dark brown freckles with burning on the exposed parts as well as on the unexposed parts of the body, ie the chest, back, abdomen and arms including other associated cutaneous and ocular changes such as ulcers and malignancy Of 36 patients, three (83%) were classified as mild, nine (25%) moderate and 24 (667%) severe; there were 18 males and 18 females, age range 2-30 years (mean 89 years) Seventeen patients had cutaneous changes: actinic keratosis, keratoacanthoma, fissures and ulcerative nodules on the exposed parts of the body Four patients had wide ulcers, along with mass formation and severe pigmentation on the face, neck and head Twenty-nine patients developed ocular symptoms: photophobia, conjunctivitis, corneal keratitis and lid ulcer One patient had complete loss of vision Histopathological findings revealed that six patients had squamous cell carcinoma (SCC) on the face, head, ear or lip More than one sibling (two to four) was affected in four families The majority of cases (20/36, 556%) were from the Brohi tribe (skin type III), while the remaining cases (16/36, 444%) were from the Sindhi population (skin type IV) The large number of XP patients seen in those with skin type III (Brohi tribe) compared with skin type IV (Sindhi population) indicates that the skin type and the race has a considerable value in the pathogenesis of XP Furthermore, 24 of 36 patients were in the severe group and six of these had SCC Moreover, no neurological abnormalities were observed in our patients All patients were treated according to disease severity by prescribing oral antibiotics, local steroids, sunscreens and/or chemotherapy followed by irradiation in malignant cases Two patients died because of extensive SCC

A.M. Bhutto

Papers

Incidence of xeroderma pigmentosum in Larkana, Pakistan: a 7-year study.