SPG20 mutation in three siblings with familial hereditary spastic paraplegia

Abstract

Troyer syndrome (MIM#275900) is an autosomal recessive form of complicated hereditary spastic paraplegia. It is characterized by progressive lower extremity spasticity and weakness, dysarthria, distal amyotrophy, developmental delay, short stature, and subtle skeletal abnormalities. It is caused by deleterious mutations in the SPG20 gene, encoding spartin, on Chromosome 13q13. Until now, six unrelated families with a genetically confirmed diagnosis have been reported. Here we report the clinical findings in three brothers of a consanguineous Moroccan family, aged 24, 17, and 7 yr old, with spastic paraplegia, short stature, motor and cognitive delay, and severe intellectual disability. Targeted exon capture and sequencing showed a homozygous nonsense mutation in the SPG20 gene, c.1369C>T (p.Arg457*), in the three affected boys.

Dwarfism in Troyer syndrome: a family with SPG20 compound heterozygous mutations and a literature review

“…Intriguingly, the brother in our study was diagnosed with Troyer syndrome combined with GHD, a phenomenon that has never been reported before. Most patients with Troyer syndrome have been observed to have mild atrophy of the vermiform lobe and hyperintensity of white matter around the ventricles on T2‐weighted imaging on brain MRI, but some patients have normal brain MRI findings . Our findings indicate that 84.2% of patients have abnormal brain MRIs, so MRI is valuable for diagnosis.…”

“…Many studies have reported that these patients have delayed milestones; however, because of their severe and progressive neurological symptoms, their short stature has not received much attention. 13,20 Our study focused on the issue and found most of these patients had extremely short stature.…”

“…With the development of genetic testing technology, Troyer syndrome has been found in a variety of ethnic populations since the first case of Troyer syndrome was reported in 1967, and new mutations in SPG20 have been detected. Through May 1, 2019, 69 cases of Troyer syndrome from 24 families have been reported globally, including 67 cases with available clinical data and 62 cases with a clear genetic diagnosis …”

“…Through May 1, 2019, 69 cases of Troyer syndrome from 24 families have been reported globally, including 67 cases with available clinical data and 62 cases with a clear genetic diagnosis. 1,[12][13][14][15][16][17][18][19][20][21] We reviewed the previously reported Troyer syndrome patients and found that the condition is most commonly found in consanguineous unions, which accounts for 75% (18/24) The proportions of meaningful clinical performance and auxiliary inspections are shown in Table 1. From the chart, we can see that all patients have spastic dysarthria and abnormal gaits, followed by lower limb spasticity (93.8%), distal amyotrophy (92.1%), short stature (90.9%), mental retardation (88.9%), skeletal abnormalities (87.9%), drooling (72.0%), emotional lability (69.8%), cerebellar signs (60.0%), upper limb spasticity (48.4%), and a unique facial appearance (38.9%).…”

Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin

“…Spartin is conserved throughout multicellular eukaryotes, although expressed in all tissues, it seems to be of particular importance in neurons. This may explain the HSP-associated symptoms in the absence of the protein 2 3 4 5 6 . The medical relevance of spartin goes beyond neurodegeneration, since the epigenetic silencing via hypermethylation of SPG20 is associated with colorectal and gastric cancer.…”