Genetic Myopathy and Mental Health Crisis: A Case Study of Severe Depression and Suicidality

This case report details the complex psychiatric and psychosocial challenges encountered by an 18-year-old man diagnosed with RYR1-related congenital myopathy (RYR1-CMYO), a rare inherited neuromuscular disorder, who presented with a severe major depressive episode and active suicidal ideation. RYR1-CMYO is characterized by considerable clinical and histopathological heterogeneity, and while chronic physical disability is known to impose a substantial psychological burden, the specific psychiatric manifestations within this patient population remain insufficiently characterized in the existing literature. The patient, who was diagnosed with RYR1-CMYO with an autosomal dominant family pattern, was admitted to a hospital setting due to a profound depressive episode accompanied by a concrete suicide plan. Furthermore, he met diagnostic criteria for obsessive-compulsive disorder (OCD) and had retrospectively reported psychotic symptoms of uncertain timing and duration, although no active psychotic symptoms were observed during the documented clinical examination.

The clinical presentation of the patient was multifaceted, encompassing both severe somatic impairment and profound psychological distress. Somatically, he suffered from a longstanding neuromuscular disability, evidenced by a history of neonatal respiratory distress syndrome, marked hypotonia, and requiring orthopedic interventions such as bilateral Achilles tendon tenotomy in 2012. By 2025, he exhibited predominantly proximal motor deficits in the lower limbs, requiring a cane for ambulation outside the home, and demonstrating significant functional limitations, quantified by a Modified Katz Activities of Daily Living (ADL) score of 9/10 and a Barthel score of 85/100. Neurological examination confirmed proximal motor deficits, an inability to perform functional maneuvers like standing from a seated position without support, and gait disturbances characterized by postural asymmetry. These motor deficits were accompanied by somatic comorbidities, including thoracic kyphosis, lumbar hyperlordosis, ‘S’-shaped scoliosis, and class I obesity (BMI 31.5 kg/m2). These physical limitations formed the backdrop against which his severe psychiatric symptoms unfolded, contributing to his overall functional impairment.

From a psychiatric perspective, the patient’s clinical history revealed a constellation of symptoms that led to a diagnosis of severe major depressive disorder (MDD) and OCD according to DSM-5-TR criteria in 2025. His depressive symptoms included persistent depressed mood, marked anhedonia, fatigue, decreased self-esteem, feelings of worthlessness, and guilt, coupled with active suicidal ideation and a concrete plan for self-harm. The OCD diagnosis was supported by recurrent intrusive thoughts containing anxiety-provoking content and compulsive neutralizing behaviors, specifically religious and behavioral rituals. Retrospectively, he also reported persecutory and auditory experiences. A systematic psychiatric history of both his maternal and paternal families was unavailable, which limited the assessment of familial vulnerability to mood or psychotic disorders; however, the patient’s profound resentment toward his mother—whom he perceived as responsible for transmitting the disorder—was a particularly salient psychosocial feature, arising from the context of chronic physical disability, reduced autonomy, and significant intrafamilial conflict.

The treatment strategy employed was a highly individualized multimodal approach, designed to address the complex interplay between his psychiatric and somatic conditions. Pharmacotherapy was central to this regimen, initially involving sertraline for depression and OCD, which was later augmented with an atypical antipsychotic, aripiprazole, due to residual significant symptoms and recurrent suicidal thoughts. Gabapentin was also utilized to reduce anxiety and psychic tension, and later, lamotrigine was introduced as a mood stabilizer to address affective instability. While lamotrigine and gabapentin are not standard treatments for MDD or OCD, their use here was considered an individualized, off-label adjunct, guided by established recommendations for the specific psychiatric disorders and adapted to the patient’s unique clinical context. The goal of this comprehensive care was not only the remission of depressive symptoms and reduction of suicide risk but also emotional and behavioral stabilization and social and family reintegration.

The clinical course demonstrated a gradual, partial improvement under this combined care. The patient showed a favorable response to the multimodal treatment, evidenced by a reduction in the intensity of depressive mood and a decrease in active suicidal ideation during follow-up. However, it is crucial to note that the contributions of individual interventions—whether pharmacological, psychological, or social—could not be separated, and the response is considered favorable but partial, necessitating ongoing monitoring. The patient maintained good insight and treatment adherence throughout the process, which were identified as favorable prognostic factors. Despite the partial recovery, several negative prognostic factors persisted, including the history of suicidal thoughts dating back to 2019, chronic disabling neurological disease, and ongoing difficulties in interpersonal and affective-sexual relationships.

The discussion surrounding the etiology of the patient’s psychiatric symptoms is highly nuanced. While the diagnosis of MDD and OCD met formal criteria, the available evidence does not establish a direct pathophysiological relationship between the RYR1 dysfunction and the depressive illness. Consequently, the depressive syndrome was conceptualized as a comorbid major depressive disorder occurring within the context of a chronic disabling medical condition. However, the case strongly suggests that the chronic disability, impaired autonomy, awareness of genetic transmission, and the resulting family dynamics—specifically the patient’s attribution of responsibility to his mother—may contribute significantly to his psychological distress. This highlights the critical need to consider the interaction between physical limitations, psychological adjustment, and the psychosocial weight of genetic disease awareness when assessing psychiatric morbidity in rare neuromuscular disorders.

The case underscores the importance of a systematic assessment of depression and suicide risk in patients with rare disabling neuromuscular disorders. Furthermore, the complexity of inherited conditions necessitates a multidisciplinary management approach that integrates neurological and psychiatric care with psychological support, genetic counseling, and family-oriented interventions. Formal genetic counseling was recommended to address inheritance patterns, uncertainty about disease severity, and reproductive choices, although the documentation does not confirm that the patient attended these sessions. The family-oriented work, which addressed illness perceptions, crisis planning, and family roles, should be distinguished from formal genetic counseling, yet both are vital components of a holistic care plan.

In conclusion, this report illustrates the significant psychiatric and psychosocial burden that accompanies RYR1-related congenital myopathy in young adults. While the case does not establish an RYR1-specific psychiatric phenotype, it powerfully demonstrates how chronic physical disability, reduced independence, and the psychological weight of genetic transmission can profoundly influence a patient’s mental health.

Subject of Research: Psychiatric comorbidities and psychosocial challenges in rare inherited neuromuscular disorders.

Article Title: Case Report: Severe depression and suicidality in a young patient with RYR1-related congenital myopathy

Article References: Radu, Ş. A., Vasiliu, O., & Tudor, C. (2026). Case Report: Severe depression and suicidality in a young patient with RYR1-related congenital myopathy. Frontiers in Psychiatry, 17, 1970738. https://doi.org/10.3389/fpsyt.2026.1970738

Image Credits: AI Generated

DOI: 10.3389/fpsyt.2026.1970738

Keywords: RYR1-CMYO, Major Depressive Disorder, Obsessive-Compulsive Disorder, Neuromuscular Disease, Psychosocial Burden, Genetic Counseling, Multimodal Treatment, Suicidality, Case, Report, Severe, depression