The proband, a 52-year-old Caucasian male with mild hypertension, presented to the hospital after his wife found him unconscious in his garage. He recalled doing some gardening work when he felt lightheaded before losing consciousness. The patient reported that he did not experience chest pain; however, he had a sense of foreboding before he collapsed. On physical examination, he was found to have a right-sided weakness consistent with a possible stroke; he was intubated and taken immediately for CT and MR of the head and neck. Imaging studies revealed a widespread dissection of the ascending portion of the thoracic aorta with extension into the common carotid arteries and left subclavian artery accompanied by high-grade stenosis bilaterally (secondary to the dissection). The patient was also found to have a dissection of the abdominal aorta, which extended into the iliac arteries, with apparent sparing of the renal arteries.
Emergently, he underwent repair of the dissection of the ascending aorta. He had a hemiarch replacement, as well as a graft to the right axillary artery, an aortic valve repair, and valvuloplasty. Four days postoperatively, the patient developed acute left-sided hemiparesis. MRI of the brain showed predominantly right-sided cerebral hemispheric watershed infarcts with no evidence of hemorrhage. Additionally, it was found that he had a continued narrowing of the lumen of the common carotid arteries due to dissections. Because of the fragility of the vessels and the acuteness of the situation, vascular or neuroradiology intervention was not performed, and the patient was put under observation instead.
The proband underwent extensive physical therapy and rehabilitation and remarkably has recovered full physical abilities. In the course of his evaluation, he was found to have positive ANA titers up to 1 : 640. He had a homogeneous as well as a speckled pattern. He consulted with his local rheumatologist who performed an extensive serologic workup, all of which returned normal. The patient did not have any symptoms of inflammatory arthritis, rash, oral ulcers, alopecia, photosensitivity, Raynaud's phenomenon, skin thickening, skin hardening or tightening, dysphagia, cough, shortness of breath, or symptoms of serositis.
The family history does not include any known history of sudden vascular death, although his father did pass away at age 82 of a cerebral aneurysm. The patient did not display any traits of hypermobility and denies the history of recurrent joint dislocations, poor healing of the skin, or lens dislocations. He was on low-dose lisinopril for his hypertension, and he had taken prednisone long-term for his microscopic colitis, with doses of up to 30 mg per day, but usually not more than 10 mg per day.
Heritable disorders of connective tissue (HDCT) sequencing and deletion/duplication panel was performed by a CAP-accredited/CLIA-certified laboratory to explore the possibility of a vascular form of a connective tissue disorder. This test analyzed the following genes via NextGen sequencing on an Illumina platform with concurrent exon-level oligo array CGH: ACTA2, ADAMTS2, ALDH18A1, ATP6V0A2, ATP7A, B3GALT6, B4GALT7, CBS, CHST14, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL9A1, COL9A2, DSE, EFEMP2, ELN, FBLN5, FBN1, FBN2, FKBP14, FLNA, LTBP4, MAT2A, MED12, MFAP5, MYH11, MYLK, NOTCH1, PLOD1, PRDM5, PRKG1, PYCR1, RIN2, SKI, SLC2A10, SLC39A13, SMAD3, SMAD4, TGFB2, TGFB3, TGFBR1, TGFBR2, and ZNF469 [UCSC hg19]. The test identified a heterozygous deletion of at least exons 21-34 of MYLK [3q21.1(123,332,644-123,386,568)x1 arr[GRCh37]]. The extent of the deletion was confirmed with whole-genome oligonucleotide array-based comparative genomic hybridization with single-nucleotide polymorphism analysis (CGH + SNP), arr[GRCh37] 3q21.1(123219342_123386568)x1.