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LETTERS TO EDITOR
Year : 2016  |  Volume : 64  |  Issue : 1  |  Page : 171-172

Hereditary spastic paraplegia with a thin corpus callosum due to SPG11 mutation


Department of Neurology, Sir Ganga Ram Hospital, New Delhi, India

Date of Web Publication11-Jan-2016

Correspondence Address:
Samir Patel
Department of Neurology, Sir Ganga Ram Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.173660

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How to cite this article:
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

How to cite this URL:
Patel S, Sethi PK, Anand I, Batra A, Gupta P. Hereditary spastic paraplegia with a thin corpus callosum due to SPG11 mutation. Neurol India [serial online] 2016 [cited 2022 Jan 18];64:171-2. Available from: https://www.neurologyindia.com/text.asp?2016/64/1/171/173660


Sir,

Hereditary spastic paraplegia (HSP) or Strümpell–Lorrain syndrome refers to clinically and genetically heterogeneous groups of conditions that are characterized by the presence of lower limb spasticity and weakness. Clinically, they are classified as “pure” when spastic paraplegia exists in isolation and as “complicated” when other major clinical features such as mental retardation, optic atrophy, retinopathy, ichthyosis, ataxia, deafness, cerebellar signs, muscle wasting, epilepsy, and extrapyramidal symptoms are present.[1] The genetics of HSP is complex, and all modes of inheritance (autosomal dominant, autosomal recessive, and X-linked recessive) have been described. More than 40 HSP loci have been reported.[2]

HSP with a thin corpus callosum, classified as complicated form of spastic paraplegia, is a rare neurodegenerative disorder mainly described in Japanese families, with an autosomal recessive transmission. Genetic locus was linked to chromosome 15q13-15 (SPG11 gene). SPG11 gene encodes for the protein spatacsin.[3] We report a case of a young man with HSP with a thin corpus callosum due to SPG11 mutation.

A 19-year-old young man, born out of a nonconsanguineous marriage, presented with a history of progressive difficulty in walking for the past 3 years. He had normal developmental milestones and athletic ability during childhood but had a poor scholastic performance. Histories of similar symptoms in paternal cousin sisters were present, and they became bedridden by the end of their third decade. He belonged to the Agrawal community.

The general physical examination was normal. On central nervous system examination, the patient was conscious, with evidence of impaired attention, recall, judgment, and abstract thinking, along with a mini–mental state examination score of 26/30. Examination of cranial nerves, including fundus, was unremarkable. He had a normal muscle bulk, with spasticity of lower limbs. The power in the lower limbs was Medical Research Council (MRC) grade 4/5 in all groups of muscles. Deep tendon reflexes in both upper and lower limbs were brisk, with sustained ankle clonus, and the plantar response was bilaterally extensor. Sensory system examination was normal. His gait was spastic.

His routine blood investigations including hemogram, blood sugar, renal and liver functions, and thyroid profile were normal. Serum vitamin B12 was within the normal range. Electromyography and nerve conduction studies were normal. MRI of the brain revealed a thin corpus callosum with frontoparietal cortical atrophy on T2-weighted mid-sagittal image [Figure 1]. Symmetrical periventricular white matter lesions were also seen on FLAIR images [Figure 2]. MRI of the spine done elsewhere was unremarkable. Genomic DNA was analyzed for mutation in exon 15 of the SPG11 gene and was found to be homozygous for c. 2716del C (p.Q906Sfs*15) mutation. It was consistent with the diagnosis of autosomal recessive HSP with a thin corpus callosum. Family screening and genetic counseling were advised.
Figure 1: Mid-sagittal T2-weighted MR image showing a thin corpus callosum with frontoparietal cortical atrophy

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Figure 2: Axial FLAIR image showing the symmetrical periventricular white matter lesions

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HSP with a thin corpus callosum is characterized by normal motor development, slowly progressive spastic paraparesis, and dementia developing from the early second decade along with various complicated symptoms such as spastic tetraplegia, muscular atrophy, extrapyramidal symptoms, sensory impairment, cerebellar ataxia, epileptic seizures, and an extremely thin corpus callosum on brain MRI.[4] The estimated prevalence for HSP of all types ranges from 1:100,000 to 10:100,000 depending on the geographical distribution. SPG11 mutation was found to account for 18.9% of all recessive cases.[5] The onset of spastic paraplegia occurs mainly during infancy or adolescence (age, 1–31 years). Approximately 10 years after its onset, most affected individuals have the complete clinical picture of SPG11 gene mutation. Most of the affected individuals, therefore, become wheelchair bound, one or two decades after the onset of the disease.[6]

The MRI findings include a thin corpus callosum, frontoparietal atrophy, enlargement of the lateral ventricles, and symmetrical white matter lesions. A thin corpus callosum is not specific for this syndrome, and whether or not it represents a congenital hypoplasia or a progressive atrophy remains unclear.[7] HSP with a thin corpus callosum is associated with the SPG1, SPG11, SPG15, SPG21, and SPG32 mutations.[8] The diagnostic criteria of autosomal recessive HSP with a thin corpus callosum are: (A) An autosomal recessive inheritance, (B) slowly progressive spastic paraparesis and mental impairment, (C) thinning of the corpus callosum revealed by CT/MRI, and (D) exclusion of other disorders by laboratory tests and MRI of the spine and brain.[4]

Many disorders like spinocerebellar ataxia type 12, calpainopathy, and Van der Knaap disease are reported in the Agrawal community. We recommend direct testing for the SPGII mutation in HSP with a thin corpus callosum, especially in the Agrawal community. Although HSP with a thin corpus callosum has been previously reported from India, our case is the only genetically proven case.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
McDermott C, White K, Bushby K, Shaw P. Hereditary spastic paraparesis: A review of new developments. J Neurol Neurosurg Psychiatry 2000;69:150-60.  Back to cited text no. 1
    
2.
Salinas S, Proukakis C, Crosby A, Warner TT. Hereditary spastic paraplegia: Clinical features and pathogenetic mechanisms. Lancet Neurol 2008;7:1127-38.  Back to cited text no. 2
    
3.
Stevanin G, Azzedine H, Denora P, Boukhris A, Tazir M, Lossos A, et al. SPATAX consortium. Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration. Brain 2008;131:772-84.  Back to cited text no. 3
    
4.
Okubo S, Ueda M, Kamiya T, Mizumura S, Terashi A, Katayama Y. Neurological and neuroradiological progression in hereditary spastic paraplegia with a thin corpus callosum. Acta Neurol Scand 2000;102:196-9.  Back to cited text no. 4
    
5.
Fink JK. Hereditary spastic paraplegia. Curr Neurol Neurosci Rep 2006;6:65-76.  Back to cited text no. 5
    
6.
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. 6
    
7.
Teive HA, Iwamoto FM, Della Coletta MV, Camargo CH, Bezerra RD, Minguetti G, et al. Hereditary spastic paraplegia associated with thin corpus callosum. Arq Neuropsiquiatr 2001;59:790-2.  Back to cited text no. 7
    
8.
de Bot ST, van de Warrenburg BP, Kremer HP, Willemsen MA. Child neurology: Hereditary spastic paraplegia in children. Neurology 2010;75;e75-9.  Back to cited text no. 8
    


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