Nakamura Osame syndrome




Hereditary spastic paraplegia (SPG or HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. SPG11 is a form of complicated SPG, in that it has neurologic features in addition to spasticity.

The estimated prevalence for HSP of all types ranges from 1:100,000 to 10:100,000 depending on the country.


Spastic paraplegia 11 (SPG11) is characterized by progressive spasticity and weakness of the lower limbs, atrophy of the corpus callosum, and either intellectual disability or cognitive impairment.

Onset of spastic paraplegia 11 (SPG11) occurs mainly during infancy or adolescence (age 1-31 years) and is characterized in most cases by gait disorders or less frequently by intellectual disability (IQ around 60) with learning difficulties in childhood and/or progressive cognitive decline (severe short-term memory impairment, emotional lability, childish behaviour, reduced verbal fluency, and attention deficit).  

Eye findings can include the following:

  • Macular excavation or degeneration as reported in the Kjellin syndrome [Orlén et al 2009, Puech et al 2011]
  • Strabismus
  • Cerebellar ocular signs such as abnormal saccadic pursuit and nystagmus in individuals with the longest disease duration
  • Visual evoked potentials with increased latencies and decreased amplitudes

Additional features are severe weakness, dysarthria, distal or generalized muscle wasting, and less frequently, pes cavus, scoliosis, parkinsonism, and orthostatic hypotension. Individuals with the longest disease duration may have swallowing difficulties. 


SPG11 is caused by homozygous or compound heterozygous mutation in the gene encoding spatacsin on chromosome 15q21.


SPG11 is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for at-risk pregnancies are possible when the disease-causing mutations in a family are known.


Diagnosis is based on:

  • clinical findings
  • a characteristic brain MRI pattern including thinning of the corpus callosum (TCC) and in most cases periventricular white matter alterations; and, because the combination of TCC with white matter changes is not specific to SPG11 and may also be present in all affected individuals
  • molecular genetic testing of SPG11 to confirm the diagnosis


Approximately ten years after onset, most affected individuals have the complete clinical picture of SPG11, including progressive lower-limb spasticity, atrophy of the corpus callosum with intellectual disability, and/or progressive cognitive decline. Most affected individuals become wheelchair bound one or two decades after disease onset.


Treatment of manifestations: Care by a multidisciplinary team; physiotherapy to stretch spastic muscles; anti-spastic drugs such as baclofen; botulin toxin and intrathecal baclofen for severe and disabling spasticity when oral drugs are ineffective. Urodynamic evaluation when bladder dysfunction is evident; anticholinergic drugs for urinary urgency. Treatment of psychiatric manifestations by standard protocols.

Prevention of secondary complications: Treatment of sphincter disturbances to prevent urinary tract infection secondary to bladder dysfunction.

Surveillance: Evaluation every six months to adjust physiotherapy and medications.




[3] Stevanin G, Montagna G, Azzedine H, Valente EM, Durr A, Scarano V, Bouslam N, Cassandrini D, Denora PS, Criscuolo C, Belarbi S, Orlacchio A, Jonveaux P, Silvestri G, Hernandez AM, De Michele G, Tazir M, Mariotti C, Brockmann K, Malandrini A, van der Knapp MS, Neri M, Tonekaboni H, Melone MA, Tessa A, Dotti MT, Tosetti M, Pauri F, Federico A, Casali C, Cruz VT, Loureiro JL, Zara F, Forlani S, Bertini E, Coutinho P, Filla A, Brice A, Santorelli FM. Spastic paraplegia with thin corpus callosum: description of 20 new families, refinement of the SPG11 locus, candidate gene analysis and evidence of genetic heterogeneity. Neurogenetics. 2006;7:149–56.

[4] Hehr U, Bauer P, Winner B, Schule R, Olmez A, Koehler W, Uyanik G, Engel A, Lenz D, Seibel A, Hehr A, Ploetz S, Gamez J, Rolfs A, Weis J, Ringer TM, Bonin M, Schuierer G, Marienhagen J, Bogdahn U, Weber BH, Topaloglu H, Schols L, Riess O, Winkler J. Long-term course and mutational spectrum of spatacsin-linked spastic paraplegia. Ann Neurol. 2007;62:656–65.

[5] Stevanin G, Azzedine H, Denora P, Boukhris A, Tazir M, Lossos A, Rosa AL, Lerer I, Hamri A, Alegria P, Loureiro J, Tada M, Hannequin D, Anheim M, Goizet C, Gonzalez-Martinez V, Le Ber I, Forlani S, Iwabuchi K, Meiner V, Uyanik G, Erichsen AK, Feki I, Pasquier F, Belarbi S, Cruz VT, Depienne C, Truchetto J, Garrigues G, Tallaksen C, Tranchant C, Nishizawa M, Vale J, Coutinho P, Santorelli FM, Mhiri C, Brice A, Durr A. 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.

[6] Orlén H, Melberg A, Raininko R, Kumlien E, Entesarian M, Söderberg P, Påhlman M, Darin N, Kyllerman M, Holmberg E, Engler H, Eriksson U, Dahl N. SPG11 mutations cause Kjellin syndrome, a hereditary spastic paraplegia with thin corpus callosum and central retinal degeneration. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:984–92.

[7] Puech B, Lacour A, Stevanin G, Sautiere BG, Devos D, Depienne C, Denis E, Mundwiller E, Ferriby D, Vermersch P, Defoort-Dhellemmes S. Kjellin syndrome: long-term neuro-ophthalmologic follow-up and novel mutations in the SPG11 gene. Ophthalmology. 2011;118:564–73.

[8] Del Bo R, Di Fonzo A, Ghezzi S, Locatelli F, Stevanin G, Costa A, Corti S, Bresolin N, Comi GP. SPG11: a consistent clinical phenotype in a family with homozygous Spatacsin truncating mutation. Neurogenetics. 2007;8:301–5.

[9] Fink JK. Hereditary spastic paraplegia. Curr Neurol Neurosci Rep. 2006;6:65–76.