From Genotype to Cardiac Phenotype: Cardiovascular Involvement in Syndromic and Metabolic Disorders.

Septal defects or shunts and valvular regurgitation were the most common cardiovascular findings across the cohort.

• Septal defects or shunts were found in 10 of 22 patients (45.5%)
• Valvular regurgitation was found in 9 of 22 patients (40.9%)
• These were followed by septal hypertrophy, valvular stenosis, and great-vessel or aortic abnormalities
• Findings were documented via echocardiographic phenotyping in a single tertiary center cohort in Taiwan

Valvular thickening clustered specifically in patients with mucopolysaccharidoses (lysosomal storage diseases).

• Valvular thickening was identified as a notable disease-category-specific cardiac lesion
• Mucopolysaccharidoses were among the disease categories mapped through next-generation sequencing
• The paper describes this as one of the most notable genotype-to-cardiac phenotype clustering patterns
• Lysosomal storage diseases were one of eight disease categories identified in the cohort

Elastin arteriopathy clustered specifically in patients with Williams-Beuren syndrome.

• Elastin arteriopathy was identified as a disease-category-specific cardiac lesion in Williams-Beuren syndrome
• Williams-Beuren syndrome was classified under contiguous-gene syndromes in the study framework
• This pattern was described as one of the most notable genotype-to-cardiac phenotype clusters
• The finding supports gene-specific cardiovascular surveillance protocols

Two children in the cohort had left ventricular systolic dysfunction, and one child died following an out-of-hospital cardiac arrest.

• Left ventricular systolic dysfunction was present in 2 of 22 patients (9.1%)
• One patient death was documented following out-of-hospital cardiac arrest
• These severe outcomes illustrate the life-threatening potential of cardiovascular involvement in genetic disorders
• The cohort included patients with primary cardiomyopathies and channelopathies among the eight disease categories

A review of eight years of outsourced next-generation sequencing identified 22 patients with molecularly confirmed genetic disorders and documented cardiovascular involvement.

• Data were collected from a single tertiary center in Taiwan over an eight-year period
• NGS was requested through the pediatric genetics service
• Eight disease categories were represented: lysosomal storage diseases, RASopathies, CHARGE syndrome, connective-tissue disorders, primary cardiomyopathies and channelopathies, neuromuscular disorders, contiguous-gene syndromes, and other metabolic and syndromic conditions
• Each patient's causative genotype was mapped to a structured echocardiographic phenotype
• The authors note that cardiovascular manifestations in these conditions 'are often recognized late and are rarely described collectively within a single cohort'

Several cardiac lesions clustered by disease category, supporting the use of gene-informed systematic cardiac surveillance over symptom-driven referral.

• Genotype-to-cardiac phenotype patterns were identified across multiple disease categories
• The authors conclude these patterns support 'gene-informed, systematic cardiac surveillance rather than symptom-driven referral in children with these disorders'
• Cardiovascular disease was described as 'a leading cause of morbidity and premature mortality' in these inherited disorders
• The structured mapping approach allowed identification of category-specific clustering patterns