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Case Reports
. 2024 Oct 9;25(19):10841.
doi: 10.3390/ijms251910841.

Challenging Diagnosis of a Patient with Two Novel Variants in the SYNE1 Gene

Anna Kuchina  1 , Aysylu Murtazina  1 , Artem Borovikov  1 , Dmitrii Subbotin  1 , Sergey Bardakov  2 , Maria Akhkiamova  1 , Aleksandra Nikolaeva  1 , Olga Shchagina  1 , Sergey Kutsev  1
Affiliations
Case Reports

Challenging Diagnosis of a Patient with Two Novel Variants in the SYNE1 Gene

Anna Kuchina et al. Int J Mol Sci. .

Abstract

We report a case of SYNE1-associated autosomal recessive spinocerebellar ataxia (SCAR8) presenting with a complex multisystemic phenotype, including highly elevated creatine kinase levels and lower-leg muscle atrophy. In addition to identifying two novel pathogenic variants in the SYNE1 gene, whole-exome sequencing revealed three variants of uncertain significance in the DYSF gene. Electromyography and muscle magnetic resonance imaging indicated a neurogenic pattern of muscle involvement. These findings, along with the segregation analysis of the variants, allowed us to exclude DYSF-associated muscular dystrophy; however, we cannot entirely rule out the possibility that the DYSF gene variants may act as modifiers of the patient's phenotype.

Keywords: SYNE1; ataxia; hyperCKemia; neuropathy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Clinical presentations of a patient with SYNE1-associated spinocerebellar ataxia. The images show distal muscle atrophy in the upper and lower limbs (A–С). Notable features include atrophy of the thenar and interosseous muscles of the hands, partial cutaneous syndactyly of the 4th and 5th fingers on the right hand, bilateral cone-shaped fingers, and medial deviation of the thumbs (A). Additionally, asymmetric atrophy and valgus deformity of the lower legs (B), as well as pes cavus (C), are evident.
Figure 2
Figure 2
Brain MRI of our proband. Sagittal, axial T1-weighted images and coronal T2-weighted images demonstrate atrophic changes of the cerebellum. T1WI, T1-weighted image; T2WI T2-weighted image.
Figure 3
Figure 3
Whole-body muscle MRI of a patient with SYNE1-associated spinocerebellar ataxia. T1-weighted MRI revealed diffuse fatty replacement in lower limb muscles, suggesting a neurogenic pattern. In all lower limb muscles, a moth-eaten appearance is visualized, with the exception of the adductor longus and gluteus major bilaterally. Vasti muscles, as well as the medial heads of the right gastrocnemius and soleus muscles, are more preserved. The T2 STIR-weighted images demonstrate a hyperintense signal in the posterior compartment of the lower leg muscles. There are no signs of the involvement of neck, trunk, or upper limb muscles.
See this image and copyright information in PMC

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