Objective: To describe a case of spasmodic dysphonia associated with hereditary spastic paraplegia (HSP) type 7.

Background: HSP is a heterogeneous group of inherited disorders characterized by lower limb predominant spasticity with or without weakness. HSP can be classified as uncomplicated or complicated based on the presence of other neurological or systemic features. HSP7 is an autosomal recessive disorder caused by a mutation in the SPG7 gene on chromosome 16q. HSP7 is usually complicated, with cerebellar ataxia as the most frequent additional feature. Dystonia is rarely seen in HSP7; to date only cervical dystonia has been reported.

Methods: We describe a case of a 26-year-old man who presented with a progressive gait disorder and abnormal speech. At age 17, he began to toe-walk. Over time, he developed a limping, unsteady gait with leg stiffness and falls. At age 25, his voice became progressively hoarse and strangulated without dysphagia. His parents are first cousins and a paternal uncle has global developmental delay.

Examination revealed normal strength, diffuse hyperreflexia in the arms and legs, bilateral positive Hoffmann’s reflexes, increased spastic tone in the legs with bilateral ankle clonus and upgoing toes. He had pronounced foot plantar flexion when walking. His gait did not change when running or walking backwards. His voice had a strained quality with occasional breaks on voice phonation. His voice quality normalized when laughing and the strain and breaks resolved with whispering.

Results: A brain MRI was normal. A cervical spine MRI revealed mild flattening of the cord. Nerve conduction studies and electromyography were normal. Laryngovideostroboscopy revealed normal laryngeal function with occasional spasm with connected speech.

Trio whole exome sequencing detected a homozygous, previously reported pathogenic nonsense variant, p.L78X (c.233T>A), in the SPG7 gene. Clinical Sanger sequencing confirmed the presence of the homozygous variant in the patient.

Conclusions: He is being treated with botulinum toxin injections to the larynx for spasmodic dysphonia and to the bilateral gastrocnemius for gait dysfunction, thought to be a combination of spasticity and dystonia. The injections and voice therapy successfully improved his voice.

We believe this is the first description of spasmodic dysphonia, a focal dystonia of the laryngeal muscles, in association with a SPG7 mutation.

References: van Gassen KL, van der Heijden CD, de Bot ST, et al.  Genotype-phenotype correlations in spastic paraplegia type 7:  a study in a large Dutch cohort.  Brain 2012; 135; 2994-3004.

Arnoldi A, Tonelli A, Crippa F, et al. A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia.  Hum Mutat. 2008; 29(4): 522-31.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/spasmodic-dysphonia-in-hereditary-spastic-paraplegia-type-7/