Original articleKjellin Syndrome: Long-term Neuro-ophthalmologic Follow-up and Novel Mutations in the SPG11 Gene
Section snippets
Materials and Methods
The present retrospective study was approved by the institutional review board of Lille University Hospital. All the patients were examined at this hospital. These patients had been referred to our clinic from 1987 to 2009 with a diagnosis of spastic paraplegia. The criteria for the clinical diagnosis of Kjellin's syndrome were maculopathy and neurologic signs, including spasmodic paraplegia. All the participants agreed to undergo neurologic and eye examinations, together with a questionnaire,
Case 1
This female patient had displayed spastic paraparesis since the age of 14 years. She was the second of 2 children (Fig 1, available at http://aaojournal.org). Her parents did not display any neurologic disorders and were not consanguineous, although they did originate from villages just 4 to 5 km apart in the remote Portuguese countryside. A far cousin on the mother's side, V14, and 2 other cousins, V16 and V17, were affected by spastic paraplegia. This distant family was studied in Portugal,
Molecular Genetics
We identified 5 (3 novel) truncating mutations in the SPG11 gene in all 4 sampled cases, in either the homozygous or the compound heterozygous state, indicating that they were the cause of the disease in these patients. They were absent from 192 French and 96 North-African unrelated healthy individuals. Two of these mutations had already been reported: The heterozygous truncating c.6832_6833delAG/p.S2278LfsX61 (exon 37) mutation found in case 7 had been reported to be segregating in affected
Discussion
Kjellin's syndrome is rare but not exceptional. Our 7 patients, all of whom carried mutations in SPG11, belonged to 6 families with a total of 14 affected members. We detected these patients in a general population of 4 million inhabitants (Nord-Pas-de-Calais Region in Northern France) over a period of 16 years. During a similar period in the same population, we identified a similar number of patients with Refsum disease.14
From a neurologic point of view, and on the basis of our observations,
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Cited by (27)
Kjellin's syndrome: Spastic paraplegia and multifocal pattern dystrophy simulating fundus flavimaculatus
2022, Archivos de la Sociedad Espanola de OftalmologiaOphthalmological changes in hereditary spastic paraplegia and other genetic diseases with spastic paraplegia
2020, Journal of the Neurological SciencesLoss of spatacsin function alters lysosomal lipid clearance leading to upper and lower motor neuron degeneration
2017, Neurobiology of DiseaseHereditary spastic paraplegia: More than an upper motor neuron disease
2017, Revue NeurologiqueCitation Excerpt :Atrophy of the corpus callosum can be detected by MRI in 41–77% of patients carrying SPG11 mutations [43]. Cerebellar ataxia and retinopathy are also frequent [43,46]. Onset is usually during infancy or adolescence.
Differentiating drusen: Drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes
2016, Progress in Retinal and Eye ResearchCitation Excerpt :Similar to ABCA4 retinopathy, electrophysiological changes may not be easily predicted from the anatomical changes, as those with widespread flecks may have normal results, or show reduction in full field ERG a wave amplitude with increased latency. Despite many similarities, Kjellin syndrome is not confused with Stargardt disease as neurological signs and symptoms predate the retinal changes (Puech et al., 2011). Recently two genes, ZFYVE26 and SPG11, have been identified where bi-allelic mutation results in Kjellin syndrome (Hanein et al., 2008; Orlen et al., 2009).
Clinical and genetic heterogeneity in hereditary spastic paraplegias: From SPG1 to SPG72 and still counting
2015, Revue NeurologiqueCitation Excerpt :ID or cognitive deterioration are observed in > 80% of SPG11 patients [90,99]. Other frequent associated clinical signs include axonal sensory-motor neuropathy, cerebellar symptoms (nystagmus, dysarthria, saccadic pursuit) and, to a lesser extent, extrapyramidal symptoms and retinopathy [14,71,90,103]. The progression of motor symptoms in SPG11 HSP is more severe than in pure phenotypes, since two-third of patients are wheelchair bound or need assistance for walking after a mean disease duration of 15 years [90].
Manuscript no. 2009-1345.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Funding: French National Research Agency (ANR) grants to G. Stevanin: A05221DS, R09148DS, and R07077DS. The funding organization had no role in the design or conduct of this research.
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The first 3 authors contributed equally to this work.