Deepika vegiraju: Created page with "== '''Alternate names''' == SPG2; SPPX2 == Definition == A rare, X-linked leukodystrophy characterized primarily by spastic gait and autonomic dysfunction. When addit..."

2021-04-21T14:06:12Z

Created page with "== '''Alternate names''' == SPG2; SPPX2 == Definition == A rare, X-linked leukodystrophy characterized primarily by spastic gait and autonomic dysfunction. When addit..."

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== '''Alternate names''' ==
SPG2; SPPX2

== Definition ==
A rare, X-linked leukodystrophy characterized primarily by spastic [[gait]] and [[autonomic dysfunction]]. When additional [[central nervous system (CNS)]] signs, such as intellectual deficit, [[ataxia]], or extrapyramidal signs, are present, the syndrome is referred to as complicated SPG.

== '''Epidemiology''' ==
* The prevalence and incidence of SPG2 have not been reported, but as part of the [[Pelizaeus-Merzbacher disease|Pelizaeus-Merzbacher]] spectrum, SPG2 roughly accounts for about 20 % of cases.
* There have been approximately 20 cases published on SPG2.
* SPG2 affects males but some female heterozygotes presenting in adulthood with a milder phenotype have also been reported.

== '''Cause''' ==
* SPG2 is due to missense substitutions affecting the '''PLP1 gene'''.
* '''PLP1 encodes the proteolipid protein (PLP)''', the most abundant protein of the myelin sheath in the central nervous system, and its alternatively spliced isoform (DM20).
* SPG2 is allelic to [[Pelizaeus-Merzbacher disease]] that is also due to PLP1 mutations.

== '''Inheritance''' ==
[[File:X-linked recessive (2).svg|thumb|right|upright=1.75|X-linked recessive inheritance]]
Transmission is [[X-linked recessive]].

== '''Signs and symptoms''' ==
* SPG2 spans a continuum of phenotypes that goes from pure to complicated SPG2.
* Pure SPG2 manifests as early as infancy or early childhood (<5 years) but may be delayed until early adulthood.
* It presents with weakness, [[hyperreflexia]], [[Babinski sign]] and spastic gait due to [[spastic paraparesis]].
* [[Autonomic dysfunction]] (spastic urinary bladder and possibly bowel, with increased urinary and fecal frequency and incontinence) is frequent.
* Patients are able to walk and their speech is normal.
* There is no CNS involvement and no [[cognitive]] decline.
* Complicated SPG2 shares the same features as SPG2 but also shows additional CNS involvement like [[nystagmus]], and [[ataxia]] that present in the first years of life.
* [[Optic atrophy]] may be present.
* Patients can also show a mild intellectual deficit.

== '''Diagnosis''' ==
* Diagnosis is based on clinical, electrophysiologic, and neuroradiological findings.
* White matter [[N-acetyl aspartate]] levels are reduced.
* Brain [[magnetic resonance imaging (MRI)]] reveals patchy or diffuse hypomyelination on T2-weighted images.
* Patients with pure SPG2 can have very subtle T2 hyperintensity.
* Other MR techniques, including MR [[spectroscopy]] and diffusion tensor imaging are useful in the diagnosis of the disease.
* Molecular [[genetic testing]] of PLP1 confirms the diagnosis.

'''Antenatal diagnosis'''
Prenatal genetic testing is possible when a family's underlying PLP1 mutation has been identified.

== '''Treatment''' ==
* A son born to a female carrier has a 50% risk of inheriting the mutation and developing the disease, while a daughter has a 50% risk of being a carrier.
* All daughters of an affected male will be carriers but none of his sons will be affected.
* Management is multidisciplinary and involves [[Neurologist|neurologists]], [[Physical therapist|physical therapists]], and [[orthopedic]] doctors.
* Treatment may include [[Antiepileptic drug|antiepileptic drugs]] for [[seizures]], and [[physical therapy]] with antispasticity drugs ([[baclofen]], [[diazepam]], [[tizanidine]], [[botulinum toxin]], [[dantrolene]]) for [[spasticity]].
* Regular surveillance is necessary.

== '''Prognosis''' ==
Pure SPG2 patients show a normal life expectancy. In complicated SPG2 cases, patients deteriorate neurologically leading to a shorter life expectancy (between the fourth and seventh decade) typically from aspiration pneumonia, pulmonary embolism and other complications of generalized weakness.

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Spastic paraplegia 2 - Revision history

Deepika vegiraju: Created page with "== '''Alternate names''' == SPG2; SPPX2 == Definition == A rare, X-linked leukodystrophy characterized primarily by spastic gait and autonomic dysfunction. When addit..."