Table 3. A summary of various metabolic and genetic conditions associated with strokes and associated imaging findings.

Risk category/conditions	Associated important clinical and imaging findings
Coagulopathies	Disorders of Protein C, S, plasminogen, anti-thrombic, fibrinogen deficiency and anti cardiolipin antibodies
	Polycythemia, anemia and platelet disorders are also risk factors
Homocystenuria and homocystenemia	Deficiencies of B6, B9 and B12 can lead to high homocysteine levels
	Rarely can be genetic in nature, and can be associated with heritable ectopia lentis
	High homocysteine levels is a risk factor of cardiovascular disease and thrombosis
MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes)	A mitochondrial cytopathy, inherited purely from female parent
	Presents with multiple stroke like episodes, the involved cerebral parenchymal does not confirm to vascular territories
	Infarcts of differing ages ‘shifting pattern spread’
	Increased diffusivity on DWI sequences, indicating a mix of vasogenic and cytotoxic oedema
ACTA2 mutation (Figure 2)	An occlusive vasculopathy with distinct clinical and angiographic findings. Chronically fixed dilated pupils is a characteristic clinical marker
	On imaging, dilatation of the proximal ICA and straightening and occlusion/narrowing of terminal ICA, straight ‘broomstick like’ arteries of Circle of Willis and a lack of lenticulostriate collaterals
	Small vessel disease and supratentorial infarctions are also observed
Notch 3 mutation (CADASIL)	An autosomal dominant microvasculopathy
	Mainly leads to small vessel involvement but can also lead to aortic disease, coronary artery disease, stroke, moyamoya disease and multisystemic smooth muscle dysfunction
	On MR imaging, extensive white matter T2W hyperintensity, with classical anterior temporal lobe and external capsular predilection
	The autosomal recessive counterpart CARASIL has a milder outlook with stroke-like episodes usually from the 3rd decade
ABCC6 mutation (Pseudoxanthoma elasticum)	Autosomal recessive mutation
	Often affects skin first with papular lesions and skin laxity
	Presents with a range of cerebral manifestations, including ischaemic stroke, small vessel disease and aneurysms
COL4A (1 and 2) related disorders	Generally hereditary, autosomal dominant conditions, although may be sporadic
	May present with intracranial haemorrhage perinatally leading to porencephaly, leukoaraiosis with CNS dysfunction, or lacunar infarcts and small vessel related disease
JAG1 mutation (Alagille syndrome)	An autosomal dominant multisystemic disorder where patients may present with ischaemic or haemorrhagic stroke, in addition to chronic cholestasis and dysmorphic facial features
	Notch 2 mutation has also been reported in Alagille syndrome
ATP7A mutation (Menke’s disease/trichopoliodystrophy)	An X-linked recessive disorder involving genes coding for copper transport
	Sparse and friable hair is a unique feature, hence is also termed ‘kinky-hair syndrome’
	On neuroimaging, tortuous intracranial vessels, extra-axial collections, and a predilection for strokes (both ischaemic and haemorrhagic have been described
SLC2A10 mutation (arterial tortuosity syndrome)	An autosomal recessive disorder which leads to occlusive arteriopathy
	Tortuosity of the aorta and large vessels is also described
GLA mutation (Fabry’s disease)	An X linked lysosomal disorder which leads to small vessel ischaemia, strokes, and multi-infarct dementia
	Basilar artery dolichoectasia is also a characteristic imaging finding
ELN gene mutation (Williams-Bueren syndrome)	Most patients have supravalvular aortic stenosis
	Some children may also have occlusive cerebrovascular disease
NF1 gene mutation (Neurofibromatosis type 1)	Excessive smooth muscle cell proliferation and vascular occlusion. Imaging may reveal diffuse cerebral arteriopathy with occlusions and aneurysms
	Associated with moyamoya syndrome