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Microangiopathy and leukoencephalopathy, pontine, autosomal dominant(PADMAL)

MedGen UID:
1684781
Concept ID:
C5231411
Disease or Syndrome
Synonyms: DEMENTIA, HEREDITARY MULTI-INFARCT, SWEDISH TYPE; Pontine autosomal dominant microangiopathy with leukoencephalopathy
SNOMED CT: Pontine autosomal dominant microangiopathy with leukoencephalopathy (1173997008); PADMAL - pontine autosomal dominant microangiopathy with leukoencephalopathy (1173997008)
 
Gene (location): COL4A1 (13q34)
 
Monarch Initiative: MONDO:0032814
OMIM®: 618564

Definition

Autosomal dominant pontine microangiopathy and leukoencephalopathy (PADMAL) is a form of cerebral small vessel disease (CSVD) resulting in the onset of recurrent ischemic strokes in the thirties or forties. Affected individuals develop progressive, but variable, cognitive and motor impairment, consistent with progressive multi-infarct dementia. Brain imaging shows lacunar infarcts, often with a pontine predilection, as well as diffuse leukoencephalopathy affecting various brain regions. Although there are overlapping clinical features, the disorder is genetically and pathologically distinct from CADASIL (125310) (summary by Verdura et al., 2016). [from OMIM]

Clinical features

From HPO
Cognitive impairment
MedGen UID:
90932
Concept ID:
C0338656
Mental or Behavioral Dysfunction
Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Postural instability
MedGen UID:
334529
Concept ID:
C1843921
Finding
A tendency to fall or the inability to keep oneself from falling; imbalance. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, Use of the retropulsion test includes a rapid balance perturbation in the backward direction, and the number of balance correcting steps (or total absence thereof) is used to rate the degree of postural instability. Healthy subjects correct such perturbations with either one or two large steps, or without taking any steps, hinging rapidly at the hips while swinging the arms forward as a counterweight. In patients with balance impairment, balance correcting steps are often too small, forcing patients to take more than two steps. Taking three or more steps is generally considered to be abnormal, and taking more than five steps is regarded as being clearly abnormal. Markedly affected patients continue to step backward without ever regaining their balance and must be caught by the examiner (this would be called true retropulsion). Even more severely affected patients fail to correct entirely, and fall backward like a pushed toy soldier, without taking any corrective steps.
Hyperintensity of cerebral white matter on MRI
MedGen UID:
811125
Concept ID:
C2938912
Pathologic Function
A brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter.

Professional guidelines

PubMed

Mancuso M, Arnold M, Bersano A, Burlina A, Chabriat H, Debette S, Enzinger C, Federico A, Filla A, Finsterer J, Hunt D, Lesnik Oberstein S, Tournier-Lasserve E, Markus HS
Eur J Neurol 2020 Jun;27(6):909-927. Epub 2020 Mar 20 doi: 10.1111/ene.14183. PMID: 32196841

Recent clinical studies

Etiology

Grobe-Einsler M, Urbach H, Paus S
J Stroke Cerebrovasc Dis 2020 Dec;29(12):105386. Epub 2020 Oct 22 doi: 10.1016/j.jstrokecerebrovasdis.2020.105386. PMID: 33254373
Mancuso M, Arnold M, Bersano A, Burlina A, Chabriat H, Debette S, Enzinger C, Federico A, Filla A, Finsterer J, Hunt D, Lesnik Oberstein S, Tournier-Lasserve E, Markus HS
Eur J Neurol 2020 Jun;27(6):909-927. Epub 2020 Mar 20 doi: 10.1111/ene.14183. PMID: 32196841
Verdura E, Hervé D, Bergametti F, Jacquet C, Morvan T, Prieto-Morin C, Mackowiak A, Manchon E, Hosseini H, Cordonnier C, Girard-Buttaz I, Rosenstingl S, Hagel C, Kuhlenbaümer G, Leca-Radu E, Goux D, Fleming L, Van Agtmael T, Chabriat H, Chapon F, Tournier-Lasserve E
Ann Neurol 2016 Nov;80(5):741-753. Epub 2016 Oct 19 doi: 10.1002/ana.24782. PMID: 27666438

Diagnosis

Roos J, Müller S, Giese A, Appenzeller S, Ringelstein EB, Fiehler J, Berger K, Rolfs A, Hagel C, Kuhlenbäumer G
J Neurol 2023 May;270(5):2631-2639. Epub 2023 Feb 14 doi: 10.1007/s00415-023-11590-9. PMID: 36786861Free PMC Article
Grobe-Einsler M, Urbach H, Paus S
J Stroke Cerebrovasc Dis 2020 Dec;29(12):105386. Epub 2020 Oct 22 doi: 10.1016/j.jstrokecerebrovasdis.2020.105386. PMID: 33254373
Mancuso M, Arnold M, Bersano A, Burlina A, Chabriat H, Debette S, Enzinger C, Federico A, Filla A, Finsterer J, Hunt D, Lesnik Oberstein S, Tournier-Lasserve E, Markus HS
Eur J Neurol 2020 Jun;27(6):909-927. Epub 2020 Mar 20 doi: 10.1111/ene.14183. PMID: 32196841
Zhao YY, Duan RN, Ji L, Liu QJ, Yan CZ
Stroke 2019 Sep;50(9):2307-2313. Epub 2019 Aug 1 doi: 10.1161/STROKEAHA.119.024875. PMID: 31366314
Ding XQ, Hagel C, Ringelstein EB, Buchheit S, Zeumer H, Kuhlenbäumer G, Appenzeller S, Fiehler J
J Neuroimaging 2010 Apr;20(2):134-40. Epub 2009 Jan 29 doi: 10.1111/j.1552-6569.2008.00336.x. PMID: 19187480

Prognosis

Zhao YY, Duan RN, Ji L, Liu QJ, Yan CZ
Stroke 2019 Sep;50(9):2307-2313. Epub 2019 Aug 1 doi: 10.1161/STROKEAHA.119.024875. PMID: 31366314
Verdura E, Hervé D, Bergametti F, Jacquet C, Morvan T, Prieto-Morin C, Mackowiak A, Manchon E, Hosseini H, Cordonnier C, Girard-Buttaz I, Rosenstingl S, Hagel C, Kuhlenbaümer G, Leca-Radu E, Goux D, Fleming L, Van Agtmael T, Chabriat H, Chapon F, Tournier-Lasserve E
Ann Neurol 2016 Nov;80(5):741-753. Epub 2016 Oct 19 doi: 10.1002/ana.24782. PMID: 27666438

Clinical prediction guides

Mancuso M, Arnold M, Bersano A, Burlina A, Chabriat H, Debette S, Enzinger C, Federico A, Filla A, Finsterer J, Hunt D, Lesnik Oberstein S, Tournier-Lasserve E, Markus HS
Eur J Neurol 2020 Jun;27(6):909-927. Epub 2020 Mar 20 doi: 10.1111/ene.14183. PMID: 32196841
Verdura E, Hervé D, Bergametti F, Jacquet C, Morvan T, Prieto-Morin C, Mackowiak A, Manchon E, Hosseini H, Cordonnier C, Girard-Buttaz I, Rosenstingl S, Hagel C, Kuhlenbaümer G, Leca-Radu E, Goux D, Fleming L, Van Agtmael T, Chabriat H, Chapon F, Tournier-Lasserve E
Ann Neurol 2016 Nov;80(5):741-753. Epub 2016 Oct 19 doi: 10.1002/ana.24782. PMID: 27666438
Craggs L, Taylor J, Slade JY, Chen A, Hagel C, Kuhlenbaeumer G, Borjesson-Hanson A, Viitanen M, Kalimo H, Deramecourt V, Oakley AE, Kalaria RN
Neuropathol Appl Neurobiol 2016 Feb;42(2):194-209. Epub 2015 Jun 17 doi: 10.1111/nan.12248. PMID: 25940137Free PMC Article
Craggs LJ, Hagel C, Kuhlenbaeumer G, Borjesson-Hanson A, Andersen O, Viitanen M, Kalimo H, McLean CA, Slade JY, Hall RA, Oakley AE, Yamamoto Y, Deramecourt V, Kalaria RN
Brain Pathol 2013 Sep;23(5):547-57. Epub 2013 Mar 8 doi: 10.1111/bpa.12041. PMID: 23387519Free PMC Article

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