Table 3.

Inherited Disorders to Consider in the Differential Diagnosis of RVCL-S

Differential
Diagnosis
Disorder		Gene(s)MOIClinical Features of the Differential Diagnosis Disorder
Overlapping w/RVCL-SDistinguishing from RVCL-S
CADASIL NOTCH3 AD
  • Focal neurologic symptoms
  • Progressive cognitive decline
  • Migraine
  • Mood disturbances
  • Apathy
  • White matter lesions on brain imaging
  • Positive family history
  • Clinical involvement limited to the brain
  • The pattern of white matter lesions on brain imaging differs from that in RVCL-S.
CARASAL CTSA AD
  • Ischemic stroke
  • Progressive cognitive decline
  • Extended white matter lesions on brain imaging
  • Hypertension
Hemorrhagic strokes occur frequently in CARASAL.
CARASIL HTRA1 AR
  • Stepwise deterioration in brain functions
  • Progressive cognitive decline
  • Extended white matter lesions on brain imaging
  • Positive family history
  • Spasticity in lower extremities, spondylosis deformans & alopecia
  • AR inheritance
Fabry disease GLA XL
  • Focal neurologic complaints
  • Nephropathy
  • Positive family history
  • Angiokeratomas, hypohidrosis, & corneal opacity
  • Onset usually in childhood or adolescence
  • XL inheritance; heterozygous females can be asymptomatic w/normal life span.
Neurofibromatosis 1 NF1 AD
  • Focal neurologic symptoms w/mass lesions on brain imaging
  • Seizures
  • Migraine
  • Positive family history
  • Café au lait macules, neurofibroma, plexiform neurofibroma, freckling in axillary or inguinal regions, optic glioma, Lisch noduli, & distinctive osseous lesions
  • Pattern of lesions on brain imaging differs from that seen in RVCL-S.
Systemic lupus erythematosus
(OMIM 152700)		 CTLA4
DNASE1
FCGR2A
FCGR2B
PTPN22
TREX1 		AD 1
  • Nephropathy
  • Anemia
  • Retinopathy
  • Mood disorders
  • Cognitive complaints
  • Seizures
  • Liver disease
  • Often no genetic pathogenic variant found
  • Features of vasculitis can occur, specifically cutaneous abnormalities, oral or nasal ulcers, alopecia, & arthritis.
  • Often associated w/↑ ANAs, anti-dsDNA; anti-Smith antibodies &/or antiphospholipid antibodies (anticardiolipin immunoglobin or lupus anticoagulant)
Tuberous sclerosis complex TSC1
TSC2 		AD
  • Multisystem disorder involving brain, kidney, & eye
  • Focal neurologic symptoms
  • Seizures
  • Mass lesions on brain imaging
  • Positive family history
  • Formation of hamartomas & skin& lung lesions
  • Many patients are diagnosed as children, but it is not uncommon for adults to be diagnosed.

AD = autosomal dominant; ANAs = antinuclear antibodies; AR = autosomal recessive; CADASIL = cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CARASAL = cathepsin A–related arteriopathy with strokes and leukoencephalopathy; CARASIL = cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; dsDNA = double-stranded DNA; MOI = mode of inheritance; XL = X-linked

1.

Most frequently, no genetic cause is identified.

From: Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations

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