Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Zadori D

PROVIDER: S-EPMC6940312 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Zádori Dénes D Szpisjak László L Németh István Balázs IB Reisz Zita Z Kovacs Gabor G GG Szépfalusi Noémi N Németh Viola Luca VL Maróti Zoltán Z Tóth-Molnár Edit E Oláh Judit J Vécsei László L Klivényi Péter P Kalmár Tibor T

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 20190902 1

<h4>Objective</h4>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 famil ...[more]

PMID: 31478152

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Project description:IntroductionAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) frequently leads to mononeuritis multiplex, which are characterized by distal weakness associated with sensory disturbances. Although AAV has also been reported to be associated with myopathy, the pathogenesis and characteristics remain unclear. We aimed to show the clinical and laboratory findings in AAV-associated myopathy.MethodsThis retrospective single-center study included patients with the diagnosis of AAV who had been admitted to the neurology department and had biopsy specimens of muscle and/or nerve tissue.ResultsWe identified four patients with a distinct clinical presentation of muscle weakness in the trunk and proximal limbs. The weakness resembled that of inflammatory muscle disease. These patients denied symptoms associated with neuropathy, and had normal serum creatine kinase (CK) levels. Needle electromyography (needle EMG) showed spontaneous electrical activity at rest, and results of magnetic resonance imaging (MRI) suggested inflammatory myopathy. Muscle biopsy specimens from all four patients revealed vasculitis and inflammation in proximity to the affected vessels, without any discernible characteristics of other myopathies. The patients also complained of symptoms affecting other organs, such as the ears and kidneys, which is typical of AAV cases. Remission induction therapy, such as cyclophosphamide pulse therapy in addition to oral prednisolone, were effective for all four patients. However, relapses occurred in two patients during maintenance therapy and two patients died of aspiration pneumonia.DiscussionThe clinical course of our patients might represent a subtype of AAV that is characterized by muscle weakness of the trunk and proximal extremities and arises from vasculitis within the muscles. The clinical manifestations of our patients were similar to those of patients with inflammatory myopathy with regard to the distribution of muscle weakness, MRI and needle EMG findings. However, there are notable differences between AAV associated myopathy vs. inflammatory myositis like dermatomyositis; (1) the absence of elevated CK levels, (2) the presence of complications in other organs, (3) distinct pathological findings, and (4) severe outcomes. Awareness that AAV patients with muscle involvement could have a subtype of AAV that seriously affects various organs is critical for an accurate diagnosis and effective therapeutic management.

Dataset Information

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

Objective

Case reports

Conclusions

Publications

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

Similar Datasets

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