BabyScreen+ newborn screening

Gene: FBN1

Green List (high evidence)

Well established gene-disease association.

ClinGen: 'definitive' actionability in paediatric patients

Age at onset of symptoms is variable and can appear from birth to adulthood. Ectopia lentis is often the presenting feature and occurs commonly before age 10 years. The cardiovascular features are the major source of morbidity and early mortality, specifically aortic dilation, dissection, and rupture and mitral valve prolapse with congestive heart failure. Aortic dilation progresses over time, on average 0.5-1 mm per year, with the vast majority of cases becoming evident before age 18 years.

A meta-analysis of five cohort studies among children and adolescents with MFS indicated that beta-blocker treatment decreased the rate of aortic dilation compared to no treatment (standardized mean difference: -1.30; 95% CI: -2.11 to -0.49; p=0.002). A randomized trial of 70 patients with MFS aged 12-50 years showed that beta-blocker vs. no treatment slowed the rate of aortic dissection (aortic ratio mean slope: 0.084 vs. 0.023, respectively). However, none of the studies demonstrated an impact on mortality, occurrence of aortic dissection, or the need for elective repair of the aorta and/or aortic valve, though these studies were likely underpowered.

A meta-analysis of six randomized clinical trials among children and adults with MFS indicated that losartan, an angiotensin II receptor antagonist, significantly decreased the rate of aortic dilation compared to no losartan treatment (standardized mean difference: -0.13; 95% CI: -0.25 to 0.00; p=0.04). However, improvements in mortality, cardiovascular surgery, or aortic dissection or rupture were assessed but not observed.

Ophthalmology and scoliosis surveillance also recommended; lifestyle modifications.

For review: re age of onset and treatment.

Created: 23 Nov 2022, 4:24 a.m. | Last Modified: 23 Nov 2022, 4:24 a.m.

Panel Version: 0.1031

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Marfan syndrome, MIM# 154700