Details of Disease

General Information of Disease (ID: DISFUYL2)

• Disease Name: Hereditary spastic paraplegia 4
• Synonyms: familial spastic paraplegia, autosomal dominant, 2; spastic paraplegia 4, autosomal dominant; familial spastic paraplegia autosomal dominant 2; spastic paraplegia 4; FSP2; hereditary spastic paraplegia 4; autosomal dominant spastic paraplegia type 4; SPAST hereditary spastic paraplegia; SPG4; autosomal dominant spastic paraplegia 4; hereditary spastic paraplegia type 4; hereditary spastic paraplegia caused by mutation in SPAST
• Definition: Autosomal dominant spastic paraplegia type 4 (SPG4) is a form of hereditary spastic paraplegia with high intrafamilial clinical variability, characterized in most cases as a pure phenotype with an adult onset (mainly the 3rd to 5th decade of life, but that can present at any age) of progressive gait impairment due to bilateral lower-limb spasticity and weakness as well as very mild proximal weakness and urinary urgency. In some cases, a complex phenotype is also reported with additional manifestations including cognitive impairment, cerebellar ataxia, epilepsy and neuropathy. A faster disease progression is noted in patients with a later age of onset.
• Disease Hierarchy:
  DISY0R2F: SPAST-related motor disorder
  DISGZQV1: Hereditary spastic paraplegia
  DISFUYL2: Hereditary spastic paraplegia 4
• Disease Identifiers:
  MONDO ID: MONDO_0008438
  MESH ID: C536865
  UMLS CUI: C1866855
  OMIM ID: 182601
  MedGen ID: 401097
  Orphanet ID: 100985
  SNOMED CT ID: 723820001

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC30A6	DTKPRIL	Strong	Genetic Variation	[1]

This Disease Is Related to 7 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ATL1	OTR2788Y	Strong	Genetic Variation	[2]
DPY30	OTLHCJ6C	Strong	Genetic Variation	[3]
IFT122	OTSK3OAD	Strong	Genetic Variation	[3]
NIPA1	OT9ODC8X	Strong	Genetic Variation	[4]
REEP1	OTEMVFX7	Strong	Genetic Variation	[5]
SPG11	OTZ7LJX4	Strong	Genetic Variation	[6]
SPAST	OTIF3AJI	Definitive	Autosomal dominant	[7]

References

• [1] Alu-specific microhomology-mediated deletion of the final exon of SPAST in three unrelated subjects with hereditary spastic paraplegia.Genet Med. 2011 Jun;13(6):582-92. doi: 10.1097/GIM.0b013e3182106775.
• [2] Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia.BMC Neurol. 2010 Oct 8;10:89. doi: 10.1186/1471-2377-10-89.
• [3] Partial SPAST and DPY30 deletions in a Japanese spastic paraplegia type 4 family.Neurogenetics. 2011 Feb;12(1):25-31. doi: 10.1007/s10048-010-0260-7. Epub 2010 Sep 22.
• [4] Isolation of CAG/CTG repeats from within the chromosome 2p21-p24 locus for autosomal dominant spastic paraplegia (SPG4) by YAC fragmentation.Hum Genet. 1999 Sep;105(3):217-25. doi: 10.1007/s004390051092.
• [5] Molecular spectrum of the SPAST, ATL1 and REEP1 gene mutations associated with the most common hereditary spastic paraplegias in a group of Polish patients.J Neurol Sci. 2015 Dec 15;359(1-2):35-9. doi: 10.1016/j.jns.2015.10.030. Epub 2015 Oct 17.
• [6] Are Cognitive Changes in Hereditary Spastic Paraplegias Restricted to Complicated Forms?.Front Neurol. 2019 May 24;10:508. doi: 10.3389/fneur.2019.00508. eCollection 2019.
• [7] Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. Nat Genet. 1999 Nov;23(3):296-303. doi: 10.1038/15472.