Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
The aim of this study is to determine the clinical spectrum and natural progression of
 Hereditary Spastic Paraplegias (HSP) and related disorders in a prospective multicenter
 natural history study, identify digital, imaging and molecular biomarkers that can assist in
 diagnosis and therapy development and study the genetic etiology and molecular mechanisms of
 these diseases.
The investigators will perform a registry-based standardized prospective Natural History
 Study (NHS) in HSPs and related disorders. Participants will be seen annually. At study
 visits a standardized clinical examination will be performed including application of
 clinical rating scales (selection of rating scales may vary depending on the individual
 phenotype and specific genotype); data will be entered into a clinical database (HSP
 Registry; https://www.hsp-registry.net). At all study visits, patients will be asked to
 donate biosamples; biomaterial collection is optional and participants can elect to
 participate in sampling of blood, urine, CSF, and/or a skin biopsy.

 Optionally, additional examinations may be performed including imaging, quantitative movement
 analysis, neuropsychological examinations, analysis of patient or observer reported outcomes
 and OMICS analysis to characterize molecular biomarkers.

 In participants without a genetic diagnosis, next generation sequencing may be performed.
Inclusion criteria:

 -  One of the following:

 1. Primary participant: Clinical or genetic diagnosis of HSP or a related disorder

 2. Secondary participant: Unaffected family member (1st or 2nd degree relative) of
 primary participant (with the above-mentioned restrictions for special
 populations) able to give informed consent

 3. Unrelated healthy control able to give informed consent

 AND

 -  Written informed consent

 AND

 - Participants are willing and able to comply with study procedures

 Exclusion criteria:

 -  Missing informed consent of primary or secondary participant/ healthy control/ legal
 representatives

 -  For controls: evidence of a neurodegenerative disease or movement disorders; inability
 to give informed consent