Clinical and Molecular Findings of Autosomal Recessive Spastic Ataxia of Charlevoix Saguenay: an Iranian Case Series Expanding the Genetic and Neuroimaging Spectra.

Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is now increasingly identified from all countries over the world, possibly rendering it one of the most common autosomal recessive ataxias. Here, we selected patients harboring SACS variants, the causative gene for ARSACS, in a large cohort of 137 patients with early-onset ataxia recruited from May 2019 to May 2021 and were referred to the ataxia clinic. Genetic studies were performed for 111 out of 137 patients (81%) which led to a diagnostic rate of 72.9% (81 out of 111 cases). Ten patients with the molecular diagnosis of ARSACS were identified. We investigated the phenotypic and imaging spectra of all confirmed patients with ARSACS. We also estimated the frequency of ARSACS in this cohort and described their clinical and genetic findings including seven novel variants as well as novel neuroimaging findings. While the classic clinical triad of ARSACS is progressive cerebellar ataxia, spasticity, and sensorimotor polyneuropathy, it is not a constant feature in all patients. Sensorimotor axonal-demyelinating neuropathy was detected in all of our patients, but spasticity and extensor plantar reflex were absent in 50% (5/10). In all patients, brain magnetic resonance imaging (MRI) showed symmetric linear hypointensities in the pons (pontine stripes) and anterior superior cerebellar atrophy as well as a hyperintense rim around the thalami (thalamic rim). Although infratentorial arachnoid cyst has been reported in ARSACS earlier, we report anterior temporal arachnoid cyst in two patients for the first time, indicating that arachnoid cyst may be an associated imaging feature of ARSACS. We also extended molecular spectrum of ARSACS by presenting 8 pathogenic and one variant of unknown significance (VUS) sequence variants, which 7 of them have not been reported previously. MetaDome server confirmed that the identified VUS variant was in the intolerant regions of sacsin protein encoded by SACS.

Foamy Cell Angiosarcoma in a Patient with Xeroderma Pigmentosum: A Case Report and Comprehensive Review of the Literature.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by a DNA repair defect caused by ultraviolet light and cutaneous manifestations, including solar lentigines, xerosis, actinic damage, and cutaneous neoplasms (e.g., basal cell carcinoma, squamous cell carcinoma, and melanoma). Cutaneous angiosarcoma (AS) is a rare group of aggressive skin tumors that infrequently occur in patients with XP, usually involving the scalp or face. The AS has three subtypes: idiopathic, complicating lymphedema, and post-irradiation. The AS has diverse histopathological types, and the uncommon variants are clear cell, epithelioid, granular cell, pseudo lymphomatous, verrucous, and signet-ring cell variants. Although the foamy cell variant of AS is the rarest type, its diagnosis would be really challenging due to the wide variety of differential diagnoses, especially for poorly differentiated ones. Therefore, definitive diagnosis and effective management in the early stages are crucial, and immunohistochemical (IHC) tests are essential. Here we report a 50-year-old Iranian man with AS complicating XP who presented with an ulcerative erythematous and progressive plaque. Histopathologic studies revealed foamy cells and vascular markers (i.e., CD 31 and CD 34) were positive, immunohistochemically which was found unusual features. In addition,, we review previously reported cases in the literature to provide some information on the diagnosis and management of such cases.