Widespread Skin Telangiectasias in Spinocerebellar Ataxia Type <scp>27B</scp>

A 63-year-old Swedish man with slowly progressive axial ataxia starting at age 53 years was investigated at our center. There was no clear family history of movement disorders; however, his mother was treated for scalp skin cancer, and a maternal uncle allegedly died of hematological cancer. His medical history included liver steatosis, a mild cerebrovascular lesion (CVL) without residual symptoms, hypertension, and benign prostate hyperplasia (BPH). There was no history of alcohol abuse, diabetes, or obesity (body mass index [BMI] = 23). Upon examination, his Scale for the Assessment and Rating of Ataxia (SARA) score was 13, and nystagmus was absent (Supplementary Video S1, segment 1); in addition, widespread telangiectasias were found in the conjunctiva and all limbs (Figure 1A, and 1B), confirmed by a skin biopsy (Supplementary Fig S1). Progressive cerebellar atrophy was found on neuroimaging (C–F), whereas nerve conduction velocity (NCV) and electromyography (EMG) studies were normal. Telangiectasias have been present since age 40 years, his alpha-feto protein (AFP) was slightly elevated (11 μg/L, normal value <8 μg/L). Taken together, all these findings suggested variant ataxia-telangiectasia (vA-T), however, colony survival assay (CSA) was normal and whole exome sequencing (WES) revealed no ATM gene variants. No pathogenic variants were found in genes associated with A-T-like disorders (ATLDs) or telomere biology disorders (Supporting Information document). A muscle biopsy yielded normal morphology, and enzyme activity in the respiratory chain complexes were also normal. There were no episodic exacerbations of ataxia. At age 73 years, his SARA score had reached 20 points, with a broad-based gait and dependency on support for mobility. Both horizontal and vertical gaze-evoked nystagmus were found (Supplementary Video S1, segment 2). Liver steatosis remained unchanged at age 66 years. Genetic re-assessment yielded a heterozygous GAA expansion in FGF14 (340 ± 10, ref < 250), establishing a diagnosis of spinocerebellar ataxia type 27B (SCA27B). 4-aminopyridine (4-AP) attenuates ataxia in SCA27B,1 but was avoided due to reduced GFR. Other than urinary urgency, attributed to BPH, there were no signs of dysautonomia or downbeat nystagmus. Since the discovery of the underlying genotype,2, 3 it has become apparent that SCA27B is common in adult-onset ataxia cohorts of diverse ethnic backgrounds, often with cerebellar atrophy and superior cerebellar peduncle hyperintensities. This is the first time SCA27B is diagnosed in the context of widespread telangiectasias. The telangiectasias are common in the general population, especially with age, and can occur in ANO10-associated ataxia, advanced liver disease, or chronic sun exposure, which was not the case here.4 Additional cases are required before considering SCA27B as a new ATLD. The authors are grateful to the patient for his kind participation and to Professor Alexander M. Taylor, Dr. Bianca Tessi, and Dr. Claes Öhberg for assistance in investigations of the patient. P. Svenningsson is a Wallenberg Clinical Scholar. M. Paucar's research is supported by Region Stockholm. M.P. contributed to the conception and design of the study. V.A., M.P., P.S., and H.T. contributed to the acquisition and analysis of data. V.A. and M.P. contributed to drafting the text or preparing the figures. Nothing to report. The data that supports the findings of this study are available in the Supporting Information of this article. Supplementary Data S1. Supplementary document. Supplementary Video S1. Segment 1 shows impaired gait, particularly when turning, mild dysmetria in all coordination tests, and mild to moderate impairment in alternating hand movements. The patient cannot perform tandem gait at this stage and his eye movements are characterized by broken smooth pursuit but no signs of nystagmus. Widespread telangiectasias are seen in the conjunctiva and in all limbs. Telangiectasias in the left shin turns pale upon pressure and recovers its initial appearance when the pressure is released. In segment 2, recorded 11 years later, ataxia has progressed. His gait has become broad-based; the patient relies on a walker for mobility, and cannot stand with his feet together. Dysarthria is mild in both segments. Dysmetria has also worsened, and the alternating hand movements are more irregular. This time horizontal and vertical gaze-evoked nystagmus was found. The patient provided consent to use a photograph of his face. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.