Progressive length-dependent polyneuropathy in xeroderma pigmentosum group A.

BACKGROUND: In this study, we aimed to investigate the progression of peripheral nervous system involvement in xeroderma pigmentosum group A (XP-A). METHODS: We performed nerve conduction studies in 17 genetically confirmed XP-A patients and conducted follow-ups. Of these patients we also analyzed gray matter volume (GMV) using brain MRI and assessed the severity score of clinical and skin manifestation. RESULTS: We found significant reduction in the motor and sensory nerve action potential amplitude and mild reduction in conduction velocity. These findings were predominant in sensory nerves and the lower limbs, were observed since early childhood, and gradually deteriorated with age. CONCLUSIONS: The electrophysiological characteristics of XP-A patients are consistent with length-dependent axonal polyneuropathy and there is progressive deterioration from early childhood.

Predominant neurological phenotype in a Hungarian family with two novel mutations in the XPA gene-case series.

OBJECTIVE: The prevalence of xeroderma pigmentosum (XP) is quite low in Europe, which may result in a delay in determining the appropriate diagnosis. Furthermore, some subtypes of XP, including XPA, may manifest themselves with quite severe neurological symptoms in addition to the characteristic dermatological lesions. Accordingly, the aim of the current study is to highlight the predominant neurological aspects of XPA, as well as mild-to-moderate dermatological signs in a Hungarian family with 5 affected siblings. CASE REPORTS: The symptoms of the Caucasian male proband started to develop at 13-14 years of age with predominantly cerebellar, hippocampal, and brainstem alterations. His elder sister and three younger brothers all presented similar, but less expressed neurological signs. The diagnostic work-up, including clinical exome sequencing, revealed 2 novel compound heterozygous mutations (p.Gln146_Tyr148delinsHis, p.Arg258TyrfsTer5) in the XPA gene. Surprisingly, only mild-to-moderate dermatological alterations were observed, and less severe characteristic ophthalmological and auditory signs were detected. CONCLUSIONS: In summary, we present the first family with genetically confirmed XPA in the Central-Eastern region of Europe, clearly supporting the notion that disturbed function of the C-terminal region of the XPA protein contributes to the development of age-dependent neurologically predominant signs. This case series may help clinicians recognize this rare disorder.

External ear nodule revealing a disseminated Kaposi disease.

Kaposi disease (KD) is an angiogenetic tumor process, characterized by its various clinical aspects. Its pathogenesis is multifactorial and it was attributed to HHV-8 infection. We report an original case of disseminated KD revealed by solitary lesion of external ear in a patient treated by corticosteroids for bullous pemphigoid.

Evaluation of Meibomian gland dysfunction using meibography in patients with xeroderma pigmentosum.

PURPOSE: To assess Meibomian gland dysfunction using meibography in patients with xeroderma pigmentosum and correlate with ocular surface changes. METHODS: This cross-sectional study evaluated patients with xeroderma pigmentosum. All patients underwent a comprehensive and standardized interview. The best-corrected visual acuity of each eye was determined. Detailed ophthalmic examination was conducted, including biomicroscopy examination of the ocular surface, Schirmer test type I, and meibography, and fundus examination was also performed when possible. Meibomian gland dysfunction was assessed by non-contact meibography using Oculus Keratograph® 5M (OCULUS Inc., Arlington, WA, USA). Saliva samples were collected using the Oragene DNA Self-collection kit (DNA Genotek Inc., Ottawa, Canada), and DNA was extracted as recommended by the manufacturer. Factors associated with abnormal meiboscores were assessed using generalized estimating equation models. RESULTS: A total of 42 participants were enrolled, and 27 patients underwent meibography. The meiboscore was abnormal in the upper eyelid in 8 (29.6%) patients and in the lower eyelid in 17 (62.9%). The likelihood of having abnormal meiboscores in the lower eyelid was 16.3 times greater than that in the upper eyelid. In the final multivariate model, age (p=0.001), mutation profile (p=0.006), and presence of ocular surface malignant tumor (OSMT) (p=0.014) remained significant for abnormal meiboscores. For a 1-year increase in age, the likelihood of abnormal meiboscores increased by 12%. Eyes with OSMT were 58.8 times more likely to have abnormal meiboscores than eyes without ocular surface malignant tumor. CONCLUSION: In the final model, age, xeroderma pigmentosum profile, previous cancer, and clinical alterations on the eyelid correlated with a meiboscore of ≥2. Meibomian gland dysfunction was common in patients with xeroderma pigmentosum, mainly in the lower eyelid. The severity of Meibomian gland dysfunction increases with age and is associated with severe eyelid changes.

Orbital myiasis complicating squamous cell carcinoma in xeroderma pigmentosum.

Ophthalmomyiasis is a rare infection seen in susceptible individuals. We report a case of orbital myiasis in squamous cell carcinoma (SCC) in a patient of xeroderma pigmentosum. On presentation, reddish brown ulcerated mass with numerous maggots in orbit were seen. Computed tomography scan showed the presence of soft tissue lesion without any bony destruction. Following debridement, emergency exenteration with sacrifice of eyelid skin was performed. The diagnosis of SCC was confirmed on histopathologic evaluation. The maggots belonged to family Calliphoridae and secondary bacterial infection with Klebsiella organism was identified. Management issues included extensive involvement requiring exenteration, non-availability of skin graft, delayed secondary healing and recurrence of pigmented lesions in skin lining of orbit. The skin grafting was avoided as it can harbour the neoplasm.

Neurochemistry evaluated by MR spectroscopy in a patient with xeroderma pigmentosum group A.

MRI of a female patient with xeroderma pigmentosum group A (XP-A) showed progressive cerebral atrophy, but no disease-specific lesion. MR spectroscopy with short TE sequences in the bilateral white matter revealed decreased N-acetyl aspartate (neuro-axonal marker) and increased myo-inositol (astroglial marker) with a normal concentration of choline (membrane marker), which are compatible with the neuropathology of XP-A, consisting of a reduced number of neurons, and fibrillary astrogliosis with preservation of myelinated fibers. MR spectroscopy reveals neurochemical derangement in XP-A, which cannot be observed on conventional MRI, and will be useful to monitor the neurochemical derangements of XP-A.

Quantitative analysis of brain atrophy in patients with xeroderma pigmentosum group A carrying the founder mutation in Japan.

INTRODUCTION: Xeroderma pigmentosum (XP) is an inherited congenital disease presenting with dermatological and neurological manifestations. In Japan, XP complementation group A (XP-A) is most frequently observed in eight clinical subtypes, and the homozygous founder mutation, IVS3-1G>C in XPA, suffer from severe manifestations including progressive brain atrophy since childhood. In this study, we used magnetic resonance imaging (MRI) and applied volumetric analysis to elucidate the start and the progression of the brain atrophy in these patients. MATERIAL AND METHODS: Twelve Japanese patients with XP-A carrying the founder mutation and seven controls were included. MRI was performed for each patient once or more. Three-dimensional T1 weighted images were segmented to gray matter, white matter, and cerebrospinal fluid, and each volume was calculated. RESULTS: Conventional MRI demonstrated progressive whole brain atrophy in patients with XP-A. Moreover, volumetric analysis showed that reductions of total gray matter volumes (GMV) and total brain volumes (TBV) started at the age of five. The slope of reduction was similar in all cases. The GMV and TBV values in controls were higher than those in XP-A cases after the age of five. CONCLUSIONS: This is the first quantitative report presenting with the progression of brain atrophy in patients with XP-A. It is revealed that the brain atrophy started from early childhood in Japanese patients with XP-A carrying the homozygous founder mutation.

Xeroderma pigmentosum complementation group F: A rare cause of cerebellar ataxia with chorea.

The complementation group F of Xeroderma pigmentosum (XP-F) is rare in the Caucasian population, and usually devoid of neurological symptoms. We report two cases, both Caucasian, who exhibited progressive cerebellar ataxia, chorea, a mild subcortical frontal cognitive impairment, and in one case severe polyneuropathy. Brain MRI demonstrated cerebellar (2/2) and cortical (1/2) atrophy. Both patients had only mild sunburn sensitivity and no skin cancer. Mini-exome sequencing approach revealed in ERCC4, two heterozygous mutations, one of which was never described (c.580-584+1delCCAAGG, exon 3), in the first case, and an already reported homozygous mutation, in the second case. These cases emphasize that XP-F is a rare cause of recessive cerebellar ataxia and can in some cases clinically mimic Huntington's disease due to chorea and executive impairment. The association of ataxia, chorea, and sun hypersensitivity are major guidance for the diagnosis, which should not be missed, in order to prevent skin neoplastic complications.

[Bronchopulmonary Kaposi's disease in 2 AIDS patients living in a zone of high tuberculosis/HIV prevalence]. / Kaposi broncho-pulmonaire au cours du SIDA en zone de forte prévalence tuberculeuse/VIH. A propos de deux cas.

The epidemic form of Kaposi's disease, called Kaposi-AIDS, was first described in 1981 by Hymmes in two young AIDS patients. Lung lesions are observed in 10 to 45% of patients with cutaneous Kaposi and are the second leading localization of visceral involvement after the digestive tract. Diagnosis and management of these visceral forms remains difficult. We report two cases of broncho-pulmonary Kaposi-AIDS in two patients treated for cutaneous Kaposi's disease. The diagnosis was made on the basis of epidemiological, clinical, biological, radiological, endoscopic, and histological evidence. The diagnosis was achieved by elimination after ruling out all other opportunistic diseases with pulmonary tropism. The fear of miliary tuberculosis remains strong in zones with a high prevalence of tuberculosis. Despite considerable improvement with antiretroviral drugs, especially antiproteases, outcome remains unpredictable with or without specific treatment.

Fibroxantoma atípico conjuntival recurrente en el xeroderma pigmentoso / Recurrent conjunctival atypical fibroxanthoma in Pigmentosum Xeroderma

Caso clínico: Un niño de 7 años con xeroderma pigmentoso presenta una recurrencia de un fibroxantoma atípico conjuntival después de 2 cirugías previas. En esta tercera intervención el paciente es tratado mediante escisión quirúrgica de la tumoración más crioterapia en el lecho. Por el riesgo de recurrencia se asoció en el postoperatorio mitomicina C 0,02% tópica con buen resultado clínico. Discusión: La exéresis quirúrgica con crioterapia y mitomicina C tópica es un tratamiento efectivo en el caso de un fibroxantoma atípico con alto potencial de recurrencia e invasión. Es necesario un seguimiento oftalmológico, así como pediátrico general en estos pacientes y asociar ayudas de apoyo (AU)

Case report: A 7 year-old boy with Xeroderma Pigmentosum (XP) and who presents a recurrent conjunctival atypical fibroxanthoma after two surgeries. This is the third procedure and the patient is treated with a surgical excision of the tumour and cryotherapy at the surgical bed. Due to the risk of recurrence, topical Mitomycin C 0,02% was added at post-operative care achieving a good clinical outcome. Discussion: Surgical exeresis with cryotherapy and topical Mitomycin C is an effective treatment for a case of an atypical fibroxanthoma with a high potential for recurrence and invasion. An ophthalmologic follow-up is required for these patients, as well as general paediatric care and support aids (AU)

Cranial computed tomography findings in xeroderma pigmentosum with neurologic manifestations (De Sanctis-Cacchione syndrome).

Computed tomography (CT) scans in two young patients with xeroderma pigmentosum with neurologic manifestations (De Sanctis-Cacchione syndrome) showed ventricular dilatation and cerebral cortical atrophy. The brainstem appeared small. In addition, an abnormal thickening of the calvarial bones was noted in both patients. These CT findings of the brain were compared with the neuropathologic features of this syndrome reported in the literature.