Facial onset sensory and motor neuronopathy: a motor neuron disease with an oligogenic origin?

Abstract

Objective: To describe a patient with facial onset sensory and motor neuronopathy (FOSMN) carrying heterozygous mutations in both TARDBP and SQSTM1 genes. Methods: The patient underwent neurological, neuropsychological, and neurophysiological examinations. Brain magnetic resonance imaging (MRI) and extensive genetic analysis were also performed. Results: The neurological examination showed dysphonia, left trigeminal hypesthesia, and left masseter and temporalis muscle atrophy. Mild cognitive impairment, affecting predominantly executive functions and social cognition, was appreciable in the neuropsychological examination. The electrophysiological studies revealed: left abnormal blink reflex; neurogenic changes in bulbar and cervical muscles; normal motor evoked potential amplitude, central motor conduction time and cortical silent period. Brain MRI showed right-predominant frontotemporal atrophy. Genetic analysis showed a heterozygous mutation in TARDBP (p.A390S) and in SQSTM1 (p.P392L), both previously described as causing amyotrophic lateral sclerosis. The SQSTM1, but not the TARDBP, mutation was found in both healthy siblings. Conclusions: Our data provide new clinical, neuroimaging, and genetic evidence that FOSMN is a neurodegenerative disease of the motor neuron disease and frontotemporal dementia spectrum, with a possible oligogenic origin. Multicentric efforts focusing on cognitive and genetic studies are necessary to confirm this hypothesis and to determine if ALS genes should be systematically screened in these patients.

Keywords:

• Amyotrophic lateral sclerosis
• fronto-temporal dementia
• facial onset sensory and motor neuronopathy
• TARDBP
• SQSTM1

Acknowledgements

We would like to thank the patient and his family for their kind participation in this study.

Ethics Approval

This study was performed in accordance with the guidelines of the ethical committee for biomedical research of Hospital La Fe and ethical standards laid down in the 1964 Declaration of Helsinki. All participants have given their informed consent.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

JFVC is funded by a Río Hortega grant (PI 17/00137) of the Instituto de Salud Carlos III (ISCIII). TSM is funded by a Prometeo grant (PI 2018/135) of the Conselleria de Sanitat. Samples were processed, preserved and delivered by the Biobank La Fe (PT13/0010/0026). The Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) is an initiative from the ISCIII.