- •We describe the association of FOXC1 gene variant to small-vessel disease of brain that can mimic MS.
- •Glaucoma with small-vessel disease of brain and dysmorphic facies is a tip off for alternative diagnoses, even if MRI of brain indicates MS.
- •Adds to a growing list of gene variants that could mimic MS.
A 34–year old Caucasian female was initially diagnosed with multiple small-vessel strokes at age 20 years which were etiologically classified as secondary to anti-phospholipid antibody syndrome (APS) although she had no history or laboratory data to suggest APS. Based on her MRI of brain findings, one of her neurologists was concerned she could have multiple sclerosis (MS) and hence the patient was referred to our clinic for further evaluation. The patient's MRI of brain showed confluent lesions in the periventricular and juxta-cortical lesions that fulfil 2017 McDonald criteria for dissemination in space. She had no symptoms other than occasional, mild headaches and had no findings to suggest clinically isolated syndrome (CIS) or MS; additionally, her cerebrospinal fluid analysis was unremarkable. Past history showed that she had undergone surgery for glaucoma, and subsequently developed bilateral sensorineural hearing loss in the third decade that was diagnosed as Meniere's disease. Her family history revealed that her son had dysmorphic facies and was small for age. He had a bifid uvula, bilaterally duplicated thumbs and scoliosis. Additionally, he had hypertelorism, a wide forehead and flattening of mid-face. Due to his complex medical presentation, whole exome sequencing (WES) was performed that revealed a maternally inherited heterozygous pathogenic frameshift in the FOXC1 gene. Genotyping of the mother showed the FOXC1 gene variant and adds to the growing list of differential diagnoses that may mimic MS in the context of radiological changes involving cerebral small vessels. This is the first report of a FOXC1 gene variant presenting with radiological features that can erroneously be interpreted as being consistent with MS.
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Published online: April 20, 2018
Accepted: April 6, 2018
Received in revised form: April 6, 2018
Received: February 11, 2018
© 2018 Elsevier B.V. All rights reserved.