Pt Sex Anatomic Site of AoD Associated Diagnoses Stated Indication for Initiation of Medication Genetic Findings Family History of aortic pathology/connective tissue disorder/CHD
1 F AAo TS Hypertension Mildly dilated AAo and BP control. Patient was switched from HCTZ to Metoprolol. Chromosome analysis: Female karyotype with Monosomy X -
2 M Aortic Root BAV AS AI FH of sudden death due to aortic dissection in father (47 yo). Pt did not meet Ghent criteria for MFS. Possibly has one of the familial thoracic aortic aneurysm and dissection syndromes TAAD Panel: Hemizygous for FNLA gene splice variant of unknown clinical significance (c.116-3 C>A, Variant IVS1-3 C>A) Father (Aortic dissection)
3 M Aortic Root Suspicion for CTD Aortic dimensions above the 95th percentile for BSA; Father died of thoracic aortic dissection (38 yo) SMAD 3 analysis: c.394A>G transition in exon 4 of SMAD3 gene of unknown clinical significance Negative TGFBR2, FBN1, MYH11 Father (Aortic dissection)
4 M Aortic Root AI FH and concern for genetic abnormality CGH: heterozygous deletion of one FBN1 allele; Copy Number LOSS in 15q21.1 - q21.3 Father (AoD - SoV 47 mm); Father’s cousin died during weight lifting from ”rupture of some sort”
5 F Aortic Root MFS Aortic root dimension at the 95th percentile for BSA ; started due to aortic root size and mitral regurgitation 1 base pair deletion in the fragment containing axon 44 and flanking sequences of FBN1 gene -
6 M Aortic root MFS MFS FBN1 gene c.2054G>A transition in exon 16 -
7 M Aortic Root MFS Atrial Tachycardia SoV greater than the 95th percentile for BSA FBN1 exon 11 mutation Father (MFS)
8 M Aortic Root MFS Hypertension MFS FBN1 Exon 41 c.5071_5073delAGA (heterozygous) Mother, Sister (MFS)
9 M Aortic root Suspicion of CTD Concern for possible CTD. Aortic root size in the upper normal limits, also dilation of the proximal descending aorta SMAD 3 Exon 4 sequencing analysis: SMAD3 variant of unknown significance at c.394A>G (mother and brother with same variant) Father (Aortic dissection) Brother (AoD) Mother, Brother (Same genetic mutation variant as pt)
10 M Aortic root AAo BAV AI FH concerning for a potential genetic etiology for cardiac findings, at risk for progression of AoD given FH CGH: 7q31.3 copy number loss; Adams-Oliver syndrome and Aarskog-Scott syndrome, which were negative by next-generation sequencing of FDG1 and NOTCH1; TAAD panel pending; WAS, DOCK8, GATA1, STAT3 and WIPF1: negative; ASXL1p.P1137L variant (unknown significance); KMT2Cp.R1095g variant (unknown significance) Maternal GF (BAV, Aortic root aneurysm requiring surgery) Maternal great GF (brain aneurysm) Paternal uncle deceased at 1 day of age (CHD)
11 F Aortic Root MFS History of VT and Palpitations treated with Sotalol (Discontinued when started on Losartan) MFS, SoV increased by 1 mm in 6 months Heterozygous likely pathogenic missense variant detected in the FBN1 gene; c.6569G>T (p.Cys2190Phe), heterozygous, exon 54 -
12
M
Aortic Root
Suspicion for CTD
Concern for MFS (Aortic root increased from 30 to 37 mm in 2 years)
TAAD panel: Heterozygous FBN2 c.1644 T>G, pAsp548Glu (D548E), variant of unknown significance. Negative FBN1, TGFBR1 and TGFBR2. Plasma homocysteine: normal Brother (Pectus abnormality) Father (high arch palate)
13 M Aortic Root Hypertension aortic root dilation, BP control CGH: Copy number gain within 16p13.11; 16p13.1 duplication, including MYH11 gene -
14 M Aortic Root MFS MFS FBN1 & TGFBR2 analysis: FBN1 gene mutation exon 25 c.3146G>A -
15 M Aortic Root - FH, echocardiogram with aortic root dimensions above the 95th percentile for BSA, decrease rate of growth of aortic sinuses TAAD Panel: Variants of unknown significance COL3A1 c.203A>G, pAsp68Gly (D68G), Heterozygous COL5A2 c.3316C>T, pArg1106Trp (R1106W), Heterozygous Father (severe aortic regurgitation, AAo aneurysm with dissection s/p mechanical aortic valve, hypertension) Brother (BAV)
16 F Aortic Root AAo BAV AS AI Aortic dimensions above the 95th percentile for BSA FBN1 & TGFBR2 analysis: FBN1 negative; TGFBR2 exon 4 c.610G>A transition (unknown significance, most likely polymorphism) Unknown, Adopted
17
F
Aortic Root AAo
BAV TS
MRA confirmed AoD, patient started on medication
Chromosome analysis: 45,X (Monosomy X)
Maternal GF (Aortic Aneurysm) Maternal uncle (MVP) Maternal cousin (BAV/AI)
18 F Aortic Root MFS MFS, considered to have mild aortic root enlargement FBN1 & TGFBR2 analysis: FBN1 exon 23 c.2849G>C; TGFBR2 negative Maternal aunt (MVP) Brother (SVT)
19 M Aortic Root LDS Type 4 LDS Level 2 sequencing: TGFB2 c.1210G>A (p.Ala404Thr) variant, heterozygous -
20 F Aortic Root LDS Type 2 LDS Next Generation Sequencing: TGFBR2 1336G>A (p.Asp446Asn) variant, heterozygous (Mutation in mosaic state in father) Father (Genetic mutation)