Introduction

Dysarthria, also known as slurred speech, is a common neurological symptom that can lead to referral to a specialist. It results from the loss of motor control over muscles involved in speech, which include impairments in articulation, phonation, resonance, and prosody [1]. Although nonspecific, it is a significant finding in clinical practice because it may be the first sign of a wide range of disorders. These include both acute acquired conditions, such as cerebrovascular accidents, and slowly progressive neurodegenerative or inherited disorders [2]. Diagnosing the various underlying causes is especially challenging when dysarthria is the initial or main symptom.

Among the most commonly employed causes of progressive dysarthria in middle-aged adults are acquired lesions (especially small-vessel disease or infarction of the brainstem) followed by demyelinating lesions such as multiple sclerosis, motor neuron disease (amyotrophic lateral sclerosis), and neurodegenerative lesions such as Parkinson's disease and atypical Parkinsonian syndromes [3]. Myasthenia gravis (neuromuscular junction disorder) can also be associated with dysarthria, which has diurnal variation. Additional considerations are metabolic causes, which include vitamin E deficiency, Wilson's disease, or thyroid dysfunction [4].

However, if the preliminary examination does not reveal the underlying cause, it should be considered to be hereditary etiologies, such as genetic disorders, especially Friedrich ataxia or spinocerebellar ataxias (SCAs). Unlike acute cerebrovascular or inflammatory causes, hereditary disorders tend to have a gradual, insidious course, often in the context of a positive family history.

Spinocerebellar ataxias: clinical and genetic overview

Spinocerebellar ataxias (SCA) are a heterogeneous group of neurodegenerative diseases that mainly manifest as progressive gait instability, clumsiness of limbs, and speech impairment [5]. Dysarthria in SCAs typically occurs in conjunction with other cerebellar symptoms, including gait instability or disturbances in oculomotor function [5]. Nevertheless, the presence of phenotypic variability is a characteristic of the disease category, and manifestations in which dysarthria present earlier have been reported in a recent study [6].

However, over 40 genetic variations of SCAs have been characterized to date, with a variety of pathogenic mechanisms that include repeat amplifications, missense mutations, and truncating mutations of neuronal survival, mitochondrial, and synaptic signaling genes [7]. Traditionally, trinucleotide repeat expansion in the ATXN1, ATXN2, and ATXN3 family of genes was thought to be the most common etiological factor. Nevertheless, following the development of next-generation sequencing, a host of new genes have been linked to it, including GDAP2 [8].

GDAP2-related ataxia

The GDAP2 protein is involved in cellular stress response pathways, and loss-of-function mutations have been associated with increased neuronal vulnerability and cerebellar degeneration [9]. The mutations in GDAP2 have been associated with a rare autosomal recessive form of ataxia termed spinocerebellar ataxia type 27 (SCAR 27). Symptoms reported included dysarthria, ataxia, stiffness, cognitive decline, and cerebellar atrophy as observed on imaging [10]. Moreover, solitary or excessively severe dysarthria is rare, but a combination of gait ataxia and speech impairment is prevalent. Recognition of such rare conditions is important, since they may be mistaken for non-hereditary conditions. Besides, SCAR 27 being rare, any new case contributes to increasing our understanding of the range of its phenotypes [11].

Diagnostic challenges and the importance of genetic testing

Identification of hereditary ataxias, especially rare ataxia forms, is still a neuronal problem. This is, in part, due to their low prevalence rate and also due to their symptom similarity to other more prevalent disorders. Without incredible cerebellar symptoms or imaging presentation, physicians might not pay attention to genetic etiology as early as they need to and therefore delayed diagnosis occurs. Traditional diagnostic means, such as MRI and neurophysiological ones, tend to be usual at an initial stage of the disease [12]. Whole-exome sequencing has significantly improved diagnostic yield in unexplained neurological disorders [13].

Diagnosis has been transformed by the introduction of next-generation sequencing, particularly whole-exome sequencing (WES). Thousands of genes can be simultaneously interrogated using WES, which can improve the diagnostic outcome in patients with idiopathic neurological syndromes [13]. In cases that could not be well established clearly by the normal investigations, which was the case, WES provided the definitive diagnosis. Importantly, genetic diagnosis not only sheds light on the definition of the clinical manifestation but also enables the offer of the concept of genetic counseling to such families, apart from informing them of the opportunity of introducing further specific gene-targeted therapies [14].

Rationale for the present case report

The case under consideration is of clinical significance for a number of reasons. First, it demonstrates a rare expression of GDAP2-related ataxia where the main and primary symptoms were progressive dysarthria, and gait ataxia was mild and spared invalidity over several years. Second, the absence of cerebellar atrophy and hence lack of MRI is that neuroimaging can also be healthy in early or unconventional instances of SCAR27. Third, the positive family history demonstrates the essence of a comprehensive evaluation of the pedigree to indicate the direction of the diagnostic suspicion. Lastly, a new GDAP2 nonsense mutation was discovered, which contributes to the increasing range of pathogenic variants and enriches the spectrum of previously known phenotypes of SCAR27.

Hereditary ataxias, in the phenomenon of progressive speech disorders, must be mentioned in the list of differentials, according to the characteristics of this illness in middle age, regardless of the lack of the usual features, such as cerebellar atrophy or the most severe complication in gait disorders. It also notes the importance of genetic testing with regard to the description of rare neurological pathological processes. By documenting and analyzing such bizarre manifestations, clinicians and researchers will have a more accurate view of the dynamic SCAR27, improved accuracy in the diagnosis, and, ultimately, a more productive impact on patient care.