Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Centogene AG, Department of Biomarker Research and Development, Rostock, Germany.
Eur J Med Genet. 2020 Sep;63(9):103992. doi: 10.1016/j.ejmg.2020.103992. Epub 2020 Jun 24.
GBA2 associated spastic paraplegia type 46 (SPG46) is an autosomal-recessive disorder associated with a clinical presentation of spastic gait, muscle weakness as well as an array of clinical symptoms including pseudobulbar palsy and progressive cognitive decline. Several neurological and non-neurological symptoms are associated with GBA2 mutations. An initial presentation with dystonia has not been reported so far. We report clinical, genetic and brain imaging findings in two siblings with hereditary spastic paraparesis. One sister presented with juvenile-onset leg spasticity and progressed to spastic tetraparesis, cervical and jaw opening dystonia, pseudobulbar symptoms and dementia. The other sister initially developed cervical dystonia in adulthood followed by gait spasticity and cognitive decline in the disease course. Molecular genetic testing revealed novel compound heterozygous variants in GBA2 in both sisters. The initial presentation with cervical dystonia and the differing clinical disease progression expand the clinical phenotype of GBA2 associated SPG46.
GBA2 相关的痉挛性截瘫 46 型（SPG46）是一种常染色体隐性疾病，其临床表现为痉挛性步态、肌无力以及一系列临床症状，包括假性延髓麻痹和进行性认知衰退。多种神经和非神经症状与 GBA2 突变相关。目前尚未有报道称以肌张力障碍为首发表现。我们报告了两例遗传性痉挛性截瘫兄弟姐妹的临床、遗传和脑部影像学发现。其中一位姐姐表现为青少年起病的下肢痉挛，逐渐发展为痉挛性四肢瘫痪、颈和下颌开口性肌张力障碍、假性延髓症状和痴呆。另一位姐姐起初在成年后出现颈性肌张力障碍，随后在病程中出现步态痉挛和认知能力下降。分子遗传学检测显示两位姐妹均存在 GBA2 的新型复合杂合变异。以颈性肌张力障碍为首发表现和不同的临床疾病进展扩展了 GBA2 相关 SPG46 的临床表型。
