Clinical variability and l-Dopa responsive Parkinsonism in hereditary spastic paraplegia 11

Genetic and phenotypic characterization of complex hereditary spastic paraplegia

“…Although in a relatively low number of patients, SPG11 was associated with parkinsonism in five cases and was l -DOPA-responsive in three cases, indicating a role for the basal ganglia in HSP, suggesting that this medication should be considered in SPG11 -associated HSP. Two patients had a positive family history of essential tremor (Case 6) and Parkinson’s disease (Case 15), an observation that has previously been made in other families ( Kang et al , 2004 ; Anheim et al , 2009 b ; Paisan-Ruiz et al , 2010 a ; Guidubaldi et al , 2011 ; Everett et al , 2012 b ). Other clinical features that we found in patients with SPG11 mutations include telangiectasia (Case 9) and bilateral cataracts (Case 21).…”

“…Variants within genes associated with Parkinson’s disease (PARK9; ATP13A2 ), neuronal ceroid lipofuscinosis (NCL; TPP1 ) and hereditary neuropathy ( DNMT1 ) were also identified. From the variants identified, nine in SPG11 , and one in FA2H and one in KIAA0196 had been previously reported ( Paisan-Ruiz et al , 2008 a , b , 2010 b ; Dick et al , 2010 ; Everett et al , 2012 a ; Bettencourt et al , 2013 ; Nowak et al , 2014 ). Variants in other non- SPG11 genes were not found in the ExAC population control database at a frequency of <10 heterozygous cases, except for Cases 38, 39, 44 and 48.…”

“…SPG11 is clinically characterized by slowly progressive spastic paraplegia and cognitive decline usually beginning before the second decade of life. Four less common distinct phenotypes have also been associated with SPG11 mutations, including Kjellin syndrome, which is a rare form of HSP with additional retinal manifestations ( Puech et al , 2011 ; Nowak et al , 2014 ), slowly progressive amyotrophic lateral sclerosis ( Orlacchio et al , 2010 ; Daoud et al , 2012 ), syndromes reminiscent of dystonia-parkinsonism ( Paisan-Ruiz et al , 2010 b ; Kara et al , 2013 ) and syndromes with prominent l -DOPA responsive parkinsonism ( Anheim et al , 2009 a ; Everett et al , 2012 a ). There have been reports of other types of spastic paraplegia being associated with improvement with l -DOPA ( Mallaret et al , 2014 ).…”

Movement disorders in hereditary spastic paraplegias

“… 44 45 In summary, there are reports that patients with SPG may present with tremors, including postural, task-specific resting, or kinetic tremors. 43 46 47 48 Descriptions regarding the treatment of these patients with SPG and tremors are scarce.…”