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Annals of Indian Academy of Neurology
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Table of Contents
LETTER TO THE EDITOR
Year : 2020  |  Volume : 23  |  Issue : 3  |  Page : 384-386
 

Hereditary spastic paraplegia with mental impairment, thin corpus callosum and amyotrophy: A road map to SPG11 contributors


Department of Neurology, SMS Medical College and Hospital, Jaipur, Rajasthan, India

Date of Submission18-Jul-2019
Date of Decision05-Sep-2019
Date of Acceptance12-Sep-2019
Date of Web Publication10-Jun-2020

Correspondence Address:
Divya Goel
4Ba19, Jawahar Nagar, Jaipur, Rajasthan - 302 004
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aian.AIAN_385_19

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How to cite this article:
Goel D, Sharma C M, Kumawat B L. Hereditary spastic paraplegia with mental impairment, thin corpus callosum and amyotrophy: A road map to SPG11 contributors. Ann Indian Acad Neurol 2020;23:384-6

How to cite this URL:
Goel D, Sharma C M, Kumawat B L. Hereditary spastic paraplegia with mental impairment, thin corpus callosum and amyotrophy: A road map to SPG11 contributors. Ann Indian Acad Neurol [serial online] 2020 [cited 2020 Jul 12];23:384-6. Available from: http://www.annalsofian.org/text.asp?2020/23/3/384/270557




Sir,

Hereditary spastic paraplegias are a genetically diverse group of disorders manifested clinically by lower limb weakness and spasticity. Harding[1] first classified HSP into pure form with lower limb spasticity, occasional and posterior column involvement, and complicated form, where the lower limb spasticity is associated with other neurological signs like amyotrophy, seizures, dementia, ataxia, deafness, extrapyramidal features, skeletal deformities and peripheral neuropathy.[2] On the basis of inheritance, it is classified as autosomal dominant, autosomal recessive or X-linked. Till date, 72 spastic gait gene (SPG) loci have been identified and numbered in order of their discovery.[3] The most common mutation associated with thin corpus callosum is in SPG 11, a cause of complicated HSP. It is characterized by spastic paraparesis with cognitive decline starting in early years of life. We report a case of complicated HSP with thin corpus callosum due to mutation in SPG 11.[2]

A 23-year-old male born out of a non-consanguineous marriage, presented with a history of progressive difficulty in walking since 2 years of age with frequent falls and irritable behaviour since 5 years of age. He had delayed developmental milestones and poor scholastic performance. The general physical examination was normal. On central nervous system examination, the patient had impaired attention, execution and judgement with mini mental status score of 24/30 and frontal assessment battery score of 13/18. He had spastic speech with elicitible jaw jerk. Bilateral optic atrophy was found on fundus examination. In addition, distal amyotrophy, bilateral pes cavus, hammer toes and spasticity present in lower limbs. Lower limb spasticity was present. Power was Medical Research Council (MRC) grade 4/5 in all groups of muscles. Deep tendon reflexes were brisk and bilateral Babinski's sign present. Sensory and cerebellar examination was unremarkable. His gait was spastic. Routine blood investigations, including liver function tests, renal profile, thyroid function tests and vitamin B12 levels were normal. Nerve conduction study and electromyography were normal. MRI of the brain revealed thin corpus callosum, generalized cortical atrophy [Figure 1] and bilateral symmetrical periventricular flaring [Figure 2] called 'ears of the lynx' sign. Thoracic spinal MRI showed thinning of the thoracic spinal cord with volume loss, but no obvious signal abnormalities [Figure 3]. Targeted gene sequencing was done showing a homozygous 2 base pair deletion in exon 36 of the SPG11 gene (chr15:;g. 44859720delAT; Depth 73x) that results in a frameshift and premature truncation of the protein 27 amino acids downstream to codon 2220 (p. Met2220AspfsTer27; ENST00000261866.7). It was consistent with the diagnosis of autosomal recessive HSP with a thin corpus callosum. Family screening and genetic counseling were advised. This variation has previously been reported in a homozygous state in a patient affected with hereditary spastic paraplegia.[2]
Figure 1: MRI brain T2W sagittal section showing thinning of corpus callosum with generalized cortical and cerebellar atrophy

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Figure 2: MRI brain FLAIR axial section showing ears of the lynx sign

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Figure 3: MRI spine T2W sagittal section showing dorsal cord thinning

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The SPG 11 gene encodes the protein spatacsin,[4] the exact function of which is unknown. The genetic locus for SPG 11 is 15q21.1. There is a retrograde degeneration of the longest nerve fibres in the corticospinal tracts and posterior columns. Lesions in SPG11 have a broader spectrum involving TCC, ear of the lynx sign, amyotrophy, cerebellar ataxia and cognitive decline. TCC is one of the commonest indicators of SPG 11. However, TCC is a nonspecific finding associated with SPG1, SPG11, SPG15, SPG21, and SPG32 mutations.[5] The presence of additional signs such as cognitive decline, amyotrophy and white matter lesions increases the chance of identifying SPG11 mutations.[6] In our case, the presence of all these signs led to the early genetic testing particularly for SPG11 mutations and clinching the clinical diagnosis in a cost effective manner. Here, we highlight the constellation of findings including clinical features of spastic paraparesis, mental retardation, amyotrophy, and MRI finding of TCC, which should prompt a targeted genetic testing for SPG11mutations.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Harding AE. Hereditary “pure” spastic paraplegia: A clinical and genetic study of 22 families. J Neurol Neurosurg Psychiatry 1981;44:871-83.  Back to cited text no. 1
    
2.
Kara E, Tucci A, Manzoni C, Lynch D, Elpidorou M, Bettercourt C. Genetic and phenotypic characterization of complex hereditary spastic paraplegia. Brain 2016;139:1904-18.  Back to cited text no. 2
    
3.
Lo Giudice T, Lombardi F, Santorelli FM, Kawarai T, Orlacchio A. Hereditary spastic paraplegia: Clinical-genetic characteristics and evolving molecular mechanisms. Exp Neurol 2014;261C: 518-39.  Back to cited text no. 3
    
4.
Stevanin G, Santorelli FM, Azzedine H, Coutinho P, Chomilier J, Denora PS, et al. Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. Nat Genet 2007;39:366-72.  Back to cited text no. 4
    
5.
Patel S, Sethi PK, Anand I, Batra A, Gupta P. Hereditary spastic paraplegia with a thin corpus callosum due to SPG11 mutation. Neurol India 2016;64:171-2.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Murugan A, Mallick AA, Dibble L, Babiker MOE. Thin corpus callosum as a diagnostic marker for hereditary spastic paraparesis due to mutations in the SPG11gene: A case report. Eur J Med Case Rep 2017;1:122-5.  Back to cited text no. 6
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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