Physical, oral, and swallowing functions of three patients with type a xeroderma pigmentosum: a report of three cases.

BACKGROUND: Xeroderma pigmentosum (XP) is an extremely rare and severe form of photosensitivity. It is classified into types A-G or V according to the gene responsible for the disease. The progression and severity of symptoms vary depending on the type. Although dysphagia caused by decreased swallowing function and dental malposition due to stenosis of the dentition in the facial and oral regions is common, it has not been reported in detail. We report three cases of type A XP, in which central and peripheral neurological symptoms appeared early on and progressed rapidly. We describe the oral function of these patients, focusing on the swallowing function and dentition malposition. CASE PRESENTATION: Two males (27 and 25 years old) and one female (28 years old) presented with diverse neurological symptoms. We focused on the relationship between the changes in swallowing and oral functions and conditions due to decline in physical function. Some effects were observed by addressing the decline in swallowing and oral functions. In particular, a dental approach to manage the narrowing of the dentition, which was observed in all three patients, improved the swallowing and oral functions and maintained the current status of these functions. CONCLUSIONS: In type A XP, early decline in oral and swallowing functions is caused by the early decline in physical function, and it is necessary to monitor the condition at an early stage.

Oral mucosa involvement in pediatric patients with xeroderma pigmentosum: a comprehensive review.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder presenting with an inability to repair UV-induced DNA damage. This can lead to the development of neoplasms affecting multiple organ systems, with onset often in childhood. Unfortunately, no cure currently exists for XP, and management strategies focus on sun protection and early intervention for malignancies. Although most skin problems in XP patients are UV induced, various oral lesions are also described. However, the literature has not extensively characterized the oral manifestations and their prognostic significance. METHODS: We conducted a comprehensive review to evaluate the prevalence and nature of oral mucosal lesions in pediatric XP patients. RESULTS: Our literature search yielded 130 pediatric XP patients with oral involvement and 210 associated tumoral or non-tumoral lesions. Squamous cell carcinoma was the most common type of oral mucosal tumor reported, with other malignancies including basal cell carcinoma, melanoma, angiosarcoma, fibrosarcoma, and trichilemmal carcinoma. CONCLUSION: Given the potential morbidity and mortality associated with oral mucosal tumors in XP patients, our study aims to raise awareness of these manifestations. Early diagnosis and treatment are crucial for managing these lesions effectively, and routine oral exams should be considered a critical component of dermatological evaluations for XP patients, especially in the pediatric age group.

Xeroderma pigmentosum group G with pellagroid rash: A rare presentation.

Xeroderma pigmentosum (XP), a heterogeneous genodermatoses, has a variable clinical spectrum ranging from mild freckling and photosensitivity to severe skeletal and neurological abnormalities and cutaneous malignancies. Herein, we present the case of a 4-year-old boy with XP group G who presented with a pellagroid rash.

Neurological disease in xeroderma pigmentosum: prospective cohort study of its features and progression.

Xeroderma pigmentosum (XP) results from biallelic mutations in any of eight genes involved in DNA repair systems, thus defining eight different genotypes (XPA, XPB, XPC, XPD, XPE, XPF, XPG and XP variant or XPV). In addition to cutaneous and ophthalmological features, some patients present with XP neurological disease. It is unknown whether the different neurological signs and their progression differ among groups. Therefore, we aim to characterize the XP neurological disease and its evolution in the heterogeneous UK XP cohort. Patients with XP were followed in the UK National XP Service, from 2009 to 2021. Age of onset for different events was recorded. Cerebellar ataxia and additional neurological signs and symptoms were rated with the Scale for the Assessment and Rating of Ataxia (SARA), the Inventory of Non-Ataxia Signs (INAS) and the Activities of Daily Living questionnaire (ADL). Patients' mutations received scores based on their predicted effects. Data from available ancillary tests were collected. Ninety-three XP patients were recruited. Thirty-six (38.7%) reported neurological symptoms, especially in the XPA, XPD and XPG groups, with early-onset and late-onset forms, and typically appearing after cutaneous and ophthalmological symptoms. XPA, XPD and XPG patients showed higher SARA scores compared to XPC, XPE and XPV. SARA total scores significantly increased over time in XPD (0.91 points/year, 95% confidence interval: 0.61, 1.21) and XPA (0.63 points/year, 95% confidence interval: 0.38, 0.89). Hyporeflexia, hypopallesthaesia, upper motor neuron signs, chorea, dystonia, oculomotor signs and cognitive impairment were frequent findings in XPA, XPD and XPG. Cerebellar and global brain atrophy, axonal sensory and sensorimotor neuropathies, and sensorineural hearing loss were common findings in patients. Some XPC, XPE and XPV cases presented with abnormalities on examination and/or ancillary tests, suggesting underlying neurological involvement. More severe mutations were associated with a faster progression in SARA total score in XPA (0.40 points/year per 1-unit increase in severity score) and XPD (0.60 points/year per 1-unit increase), and in ADL total score in XPA (0.35 points/year per 1-unit increase). Symptomatic and asymptomatic forms of neurological disease are frequent in XP patients, and neurological symptoms can be an important cause of disability. Typically, the neurological disease will be preceded by cutaneous and ophthalmological features, and these should be actively searched in patients with idiopathic late-onset neurological syndromes. Scales assessing cerebellar function, especially walking and speech, and disability can show progression in some of the groups. Mutation severity can be used as a prognostic biomarker for stratification purposes in clinical trials.

SNP Array Screening and Long Range PCR-Based Targeted Next Generation Sequencing for Autosomal Recessive Disease with Consanguinity: Insight from a Case of Xeroderma Pigmentosum Group C.

Advances in genetic technologies have made genetic testing more accessible than ever before. However, depending on national, regional, legal, and health insurance circumstances, testing procedures may still need to be streamlined in real-world clinical practice. In cases of autosomal recessive disease with consanguinity, the mutation locus is necessarily isodisomy because both alleles originate from a common ancestral chromosome. Based on this premise, we implemented integrated genetic diagnostic methods using SNP array screening and long range PCR-based targeted NGS in a Japanese patient with xeroderma pigmentosum (XP) under the limitation of the national health insurance system. SNP array results showed isodisomy only in XPC and ERCC4 loci. NGS, with a minimal set of long-range PCR primers, detected a homozygous frameshift mutation in XPC; NM_004628.5:c.218_219insT p.(Lys73AsnfsTer9), confirmed by Sanger sequencing, leading to a rapid diagnosis of XP group C. This shortcut strategy is applicable to all autosomal recessive diseases caused by consanguineous marriages, especially in scenarios with a moderate number of genes to test, a common occurrence in clinical genetic practice.

Multiple Facial Basal Cell Carcinoma With Xeroderma Pigmentosum.

Multiple basal cell carcinomas are rare in children and adolescents. Xeroderma pigmentosum (XP) is a rare autosomal recessive hereditary disease characterized by photosensitivity, changes in skin pigmentation, and early onset of skin cancer. XP is extremely rare in clinical practice, with only a few cases worldwide. XP is clinically incurable. The main goal of treating this disease is to diagnose as early as possible, educate patients to strictly avoid ultraviolet radiation for life, and follow up regularly to treat skin malignant tumors in time. The authors report a 15-year-old boy with facial multiple basal cell carcinoma with XP. Its medical history, clinical features, auxiliary examination, and surgical treatment process have great reference value for the in-depth understanding of the disease. The authors will discuss how to delay the progression of the disease and treat the existing lesions in different clinical stages of the disease in combination with the existing relevant literature.

The therapeutic dental challenge of xeroderma pigmentosum patients: case report.

Xeroderma pigmentosum (XP) is a rare genetic disease characterized by a hypersensitivity to ultraviolet (UV) radiation leading to defective deoxyribonucleic acid (DNA) repair and predisposing to skin tumorigenesis. This paper reports the safe approaches used for the dental treatment of XP patients, controlling the ultraviolet (UV) sources at the dental office. An XP 29-year-old woman was referred for oral pain and sensitivity at the service of periodontology, UV rays were checked with a UV-meter. During the examination, the patient kept her sunglasses while the practitioner was dressed in dark colors using an anti-UV filter over the surgical light. Facial dark brown pigmentations, limited mouth opening, tumor resection scar on the tongue, moderate periodontitis, and dental caries were noticed. Moderate periodontitis and dental caries were diagnosed. Treatment was planned in collaboration with the dermatologist. Soft scaling and root planning were performed in short sessions and self-curing material was used for coronary fillings after caries removal. In taking care of XP patients, particular attention should be given by dental professionals to: i) the office management for a UV-safe environment; ii) the adoption of suitable dental care and safe biomaterials with short sessions and regular controls; and iii) the adoption of personal protections by patients and practitioners.

Conjunctival "Melanoma-In-Situ''-A Rare Neoplasia of Xeroderma Pigmentosum in Indian Scenario.

A 16-year-old girl born from a nonconsanguineous marriage presented to the dermatology out-patient department with innumerable hyperpigmented macules predominantly over the photoexposed parts of her body involving the face, neck, chest, back, of forearms, hands, and legs with a history of photosensitivity and photophobia (Figure 1). These were interspersed with multiple depigmented macules over her arms and legs since, she was three years old. She also had a small pigmented mass involving the left eye present for the last 3 months. She had a family history of similar cutaneous lesions in her elder sister. There was no history of hearing loss, seizures, spasticity, or cognitive impairment.

Whole Exome Sequencing of a Patient with a Milder Phenotype of Xeroderma Pigmentosum Group C.

A 17-year-old female Korean patient (XP115KO) was previously diagnosed with Xeroderma pigmentosum group C (XPC) by Direct Sanger sequencing, which revealed a homozygous nonsense mutation in the XPC gene (rs121965088: c.1735C > T, p.Arg579Ter). While rs121965088 is associated with a poor prognosis, our patient presented with a milder phenotype. Hence, we conducted whole-exome sequencing in the patient and her family members to detect coexisting mutations that may have resulted in a milder phenotype of rs121965088 through genetic interaction. Materials and Methods: the whole-exome sequencing analysis of samples obtained from the patient and her family members (father, mother, and brother) was performed. To identify the underlying genetic cause of XPC, the extracted DNA was analyzed using Agilent's SureSelect XT Human All Exon v5. The functional effects of the resultant variants were predicted using the SNPinfo web server, and structural changes in the XPC protein using the 3D protein modeling program SWISS-MODEL. Results: Eight biallelic variants, homozygous in the patient and heterozygous in her parents, were detected. Four were found in the XPC gene: one nonsense variant (rs121965088: c.1735C > T, p.Arg579Ter) and three silent variants (rs2227998: c.2061G > A, p. Arg687Arg; rs2279017: c.2251-6A > C, intron; rs2607775: c.-27G > C, 5'UTR). The remaining four variants were found in non-XP genes, including one frameshift variant [rs72452004 of olfactory receptor family 2 subfamily T member 35 (OR2T35)], three missense variants [rs202089462 of ALF transcription elongation factor 3 (AFF3), rs138027161 of TCR gamma alternate reading frame protein (TARP), and rs3750575 of annexin A7 (ANXA7)]. Conclusions: potential candidates for genetic interactions with rs121965088 were found. The rs2279017 and rs2607775 of XPC involved mutations in the intron region, which affected RNA splicing and protein translation. The genetic variants of AFF3, TARP, and ANXA7 are all frameshift or missense mutations, inevitably disturbing the translation and function of the resultant proteins. Further research on their functions in DNA repair pathways may reveal undiscovered cellular relationships within xeroderma pigmentosum.

Xeroderma pigmentosum: case report.

OBJECTIVE: The aim of this study was to describe the disease and treatment and to alert health professionals for the identification of signs and symptoms and the need for an early diagnosis in patients with xeroderma pigmentosum (XP). CASE DESCRIPTION: An 8-year-old male patient was referred to the Joana de Gusmão Hospital (HIJG) in 2021 for evaluation and specialized care. Previously, the child was followed in his place of origin by oncologic and palliative care, where he was submitted to surgeries and chemotherapy. He was admitted to the HIJG using vismodegib, acitrein, tramadol, and solar protective measures. On physical examination, there were tumors and disseminated macular verrucous and ulcerated lesions. The imaging examination showed solid and expansive lesions on the face, and atelectasis and fibroscarring changes in the lung. The histopathological report proved the existence of melanocanthoma, carcinoma, and pyogenic granuloma. After the evaluation of the case, no surgery, chemotherapy, or radiotherapy was performed. It was decided to maintain the palliative treatment and to continue the use of tramadol for pain, and vismodegib and acitretin were used to control carcinomas and prophylactic measures. COMMENTS: The XP is a rare disease of autosomal recessive inheritance whose mechanism comes from failure in the DNA repair by exposure to ultraviolet rays, resulting in lesions on the skin and mucous membranes. They start as sunburns and can progress to melanosis, areas with altered pigmentation, premature aging, poikiloderma, and areas of high risk for neoplasms.

Management of coexisting bilateral ocular surface disease in xeroderma pigmentosum - sequence and outcomes.

PURPOSE: To report a rare presentation of bilateral, coexisting ocular surface disease in a case of Xeroderma pigmentosum and its successful management. METHODS: Case report. RESULTS: A 21-year-old male with Xeroderma pigmentosum presented with bilateral ocular surface squamous neoplasia (OSSN) along with central guttae in the right eye and corneal decompensation of the left eye. Subsequently, the patient developed dry eyes and lid margin keratinization in both eyes followed by perforation in the left eye. Sequential procedures both medical and surgical, including excision of the tumour, corneal transplantation and mucous membrane grafting addressing each of these ocular surface issues resulted in a successful outcome. There was no recurrence of the tumour over 3 years. Corneal transplantation is preferably done after a minimum of 6 months following excision. Mucous membrane grafting performed for progressive lid margin keratinization resulted in surface stabilization. CONCLUSIONS: In Xeroderma Pigmentosum, multiple ocular surface features can rarely coexist and be bilateral. Periodic evaluation of the surface for tumours, progressive dry eyes and endothelial function is recommended as a part of routine evaluation in Xeroderma pigmentosum. Surface procedures should precede intraocular intervention. Sequential management can result in successful outcomes.

Radiation therapy for squamous cell cancer of the skin in a patient with xeroderma pigmentosum.

Xeroderma Pigmentosum is an autosomal recessive disease characterized by increased sensitivity to ultraviolet radiation. Adjuvant radiotherapy (RT) is an important locoregional treatment modality for high-risk skin squamous cell cancers (SCCs). We present a case of an adult with high-risk skin SCC treated with standard adjuvant RT and followed-up for >4 years with acceptable side effects.

Cutaneous Neurocristic Hamartoma Mimicking Basal Cell Carcinoma in a Patient With Xeroderma Pigmentosum.

ABSTRACT: Neurocristic hamartomas (NCH) of cutaneous origin are especially rare congenital or acquired neoplasms that often arise through aberrant embryologic development of pluripotent neural crest cells. Clinically, they often present as pigmented macules or papules on the scalp with associated alopecia. NCHs are characterized histopathologically by dermal melanocytic, fibroblastic, and neurosustentacular components. Correct identification of this etiology is critical because of potential for malignant transformation, particularly in acquired NCHs. Our patient was a 6-year-old girl with xeroderma pigmentosum and confirmed XPC mutation followed in our dermatology clinic since the age of 3. She had a history of multiple actinic keratoses but no prior skin cancers. A 4-mm homogenous pink papule on the left frontal scalp concerning for basal cell carcinoma was noted during routine skin examination. After a 3-month course of 3 times weekly topical imiquimod, the lesion had grown to a 6 mm diameter. The patient was then referred to plastic surgery for definitive excision. Histologically, the lesion showed a well-circumscribed proliferation of spindle cells with a trabecular and nested growth pattern. Perivascular pseudorosettes were identified, as were areas that resembled well-differentiated neural tissue. The spindle cells diffusely expressed S100 protein, SOX10, and CD34, with patchy expression of Melan-A and HMB-45. PRAME was negative, and p16 was retained. Array comparative genomic hybridization was performed, and no clinically significant copy number or single nucleotide variants were detected. To the best of our knowledge, this is the first documented case in the literature of a cutaneous neurocristic hamartoma arising in a patient with xeroderma pigmentosum.

Loss of Function Variants in the XPC Causes Severe Xeroderma Pigmentosum in Three Large Consanguineous Families.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare recessively inherited disorder that presents clinical and genetic heterogeneity. Mutations in eight genes, of which seven are involved in nucleotide excision repair (NER) pathway have been reported to cause the XP. METHODS AND RESULTS: Three large consanguineous families of Pakistani origin displaying typical clinical hallmarks of XP were evaluated at clinical and molecular level. Homozygosity mapping using microsatellite markers established linkage of the families to XPC gene on chromosome 3p25.1. Sanger sequencing of the XPC gene identified a novel homozygous single bp deletion [NM_004628.5; c.1934del; p.(Pro645Leufs*5)] and two previously reported mutations that included a nonsense [c.1243 C>T; p.(Arg415*)] and a splice acceptor site (c.2251-1 G>C), all segregating with the disease phenotypes in the families. CONCLUSION: This report has extended the spectrum of mutations in the XPC gene and will also facilitate in diagnosis of XP and counselling of families inheriting it, which is the only inevitable tool for preventing the disease occurrence in future generations.

Outcomes of keratoplasty in a cohort of Indian patients with xeroderma pigmentosum.

Purpose: To evaluate the outcomes of keratoplasty for xeroderma pigmentosum (XP) performed at a tertiary eye care center. Methods: A retrospective review of medical records of those patients who were clinically diagnosed to have XP (54 eyes of 36 patients) and underwent keratoplasty; either deep anterior lamellar keratoplasty (DALK, four eyes), endothelial keratoplasty (EK, eight eyes), or penetrating keratoplasty (PK, 42 eyes) from 1994 to 2018. Results: The median age at surgery was 20.6 years (interquartile range [IQR], 14.6-27.6 years) and 20 (55.6%) were males. Graft failure occurred in 15 eyes (35.7%) in the PK group and two eyes (50%) in the DALK group; none failed in the EK group. The probability of graft survival in the PK group was 97.2% ± 2.7% at 1 year, 74.0% ± 8.0% at 2 years, and 54.8% ± 11.7% at 5 years. In the PK group, 13 eyes needed antiglaucoma medications, 11 eyes developed graft infiltrate, and 13 eyes needed secondary interventions (cataract surgery, excision biopsy, and tarsorrhaphy). In the EK group, three eyes needed secondary interventions (excision biopsy). Median postoperative endothelial cell density at the last follow-up in the PK group was 1214 cells/mm2 (IQR, 623-2277 cells/mm2). Conclusion: Despite the complexities of the ocular surface and adnexal issues in XP, keratoplasty had reasonably good outcomes. More than half of the PK grafts survived 5 years with no failures in the EK group. Regular follow-up and timely management of suture-related infections raised intraocular pressure, and suspicious ocular surface lesions, in addition to solar protection, are important for the success of keratoplasty in these eyes.