Pontine autosomal dominant microangiopathy with leukoencephalopathy (PADMAL)

Last revised by Rohit Sharma on 15 Jan 2023

Pontine autosomal dominant microangiopathy with leukoencephalopathy (PADMAL) is an autosomal dominant monogenic COL4A1-related disorder that primarily causes cerebral small vessel disease. It is a distinct entity to COL4A1 brain small-vessel disease, but very likely on the same spectrum of disease as Swedish hereditary multi-infarct dementia.

The exact prevalence is unknown, but the condition is considered very rare. The onset of symptoms is generally in young and middle-aged adults.

The clinical presentation consists of :

Unlike other COL4A1-related disorders, extra-cranial manifestations are generally not seen 4.

PADMAL is caused by a mutation to the 3' untranslated region of the COL4A1 gene, located on the long arm of chromosome 13, that normally encodes for the alpha-1 chain of type IV collagen 2,3,5. In PADMAL, this mutation leads to over-expression in COL4A1, which is distinct to mutations causing COL4A1 brain small-vessel disease which are generally missense mutations in different regions of the same gene leading to abnormal alpha-1 chain of type IV collagen synthesis 2,3,5

MRI is the investigation of choice and demonstrates the following features 1-6:

Angiographic studies are usually normal 1.

No specific disease-modifying treatment is currently available and symptomatic management and specialist screening is recommended 3,4.

General imaging differential considerations include 3,6:

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