What is the clinical evidence from this study?

Study design: Observational. Population: Inherited connective tissue disorders (Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome, Beals-Hecht syndrome, UCTD) (n=136). Intervention: Next-generation sequencing of 174 genes. Primary outcome: Genetic variants and their relationship to clinical and cardiovascular damage.

What does this research mean for the field?

Patients with inherited connective tissue disorders frequently possess coexisting genetic variants in genes related to arrhythmias, sarcomeres (such as MYBPC3), and hypercholesterolemia, alongside their primary syndrome-causing mutations. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

Evaluate the relationship between genetic variants and clinical cardiovascular damage in patients with Marfan syndrome and other connective tissue disorders.

May 31, 2026Open Access

Cardiovascular and Clinical Manifestations of Marfan Syndrome and Other Inherited Connective Tissue Disorders with Coexisting Genetic Variants

Key Result

Next-generation sequencing in 136 patients with inherited connective tissue disorders revealed frequent coexistence of genetic variants, including 25 patients with MYBPC3 variants.

Key Points

Evaluate the relationship between genetic variants and clinical cardiovascular damage in patients with Marfan syndrome and other connective tissue disorders.
Prospective study in Mexican patients with Marfan syndrome, Loeys–Dietz syndrome, Ehlers–Danlos syndrome, Beals–Hecht syndrome, and undifferentiated connective tissue disease.
Next-generation sequencing targeting 174 genes related to aortopathies and cardiomyopathies was utilized.
136 patients were studied for recurrent genetic variants including MYBPC3, FBN1, TGFBR1, and others.
Identified 25 patients with coexisting genetic variant MYBPC3 among the study groups.
Eight patients in the Marfan syndrome group presented with MYBPC3 variants alongside FBN1 mutations.
All syndromes showed coexisting genetic variants related to arrhythmias and hypercholesterolemia.

Study Design

Type

Observational (n=136)

Structured PICO

Population

136 Mexican patients with Marfan syndrome (MS), Loeys-Dietz syndrome (LDS), Beals-Hecht syndrome (BHS), Ehlers-Danlos syndrome (EDS), and undifferentiated connective tissue disease (UCTD)

Intervention

Next-generation sequencing targeting coding regions of 174 genes related to aortopathies, cardiomyopathies, arrhythmias, structural heart disease, and hypercholesterolemia

Outcome

Presence of coexisting genetic variants and their relationship to clinical and cardiovascular damagesurrogate

Patients with inherited connective tissue disorders frequently exhibit coexisting genetic variants in genes related to arrhythmias, sarcomeres, and hypercholesterolemia, highlighting significant genotypic overlap.

Abstract

Marfan syndrome (MS), Loeys–Dietz syndrome (LDS), Beals–Hecht syndrome (BHS), Ehlers–Danlos syndrome (EDS), and individuals with undifferentiated connective tissue disease (UCTD) exhibit phenotypic overlap, suggesting a likelihood of genotypic coexistence. Our objective was to evaluate genetic variants (GVs), encoding 174 genes related to aortopathies, cardiomyopathies, arrhythmias, structural heart disease, and hypercholesterolemia, and their relationship to clinical and cardiovascular damage in these syndromes. This was a prospective study in Mexican patients with MS, LDS, EDS, BHS, and UCTD. One hundred and seventy-four genes related to hereditary diseases were studied using next-generation sequencing targeting coding regions. Of the 136 patients, 25 were identified with the recurrent and coexisting GV of MYBPC3. In the MS group, in addition to the presence of GV in FBN1, eight patients had GV in MYBPC3, six in FBN2, and five in COL3A1 and COL5A1. In the LDS group, in addition to GV in TGFBR1, TGFBR2, and SMAD3, four patients presented with GV in MYBPC3 and two with FBN2. In the BHS group, in addition to FBN2, two patients had GV in MYBPC3and one with TGFBR2. In the UCTD group, nine patients had GV in MYBPC3 and two in COL5A1 and COL5A2. All syndromes coexisted with GV in genes related to arrhythmias, sarcomeres, and hypercholesterolemia. In EDS, coexistence with several sarcomere proteins was found.