Cardiac pathologies in Marfan syndrome do not correlate with specific type of mutation in FBN1 gene in childhood

Background: Marfan syndrome (MFS) is an inherited connective-tissue disorder classically caused by different mutations in FBN1 gene. In childhood specific type of mutation and its correlation with cardiac pathologies is deficient known. This study evaluates detailed mutation and association with cardiac pathology. After all we want to evaluate whether there is a need to differentiate between specific mutations concerning prognosis, follow-up and medical treatment.

Methods: We investigated 260 patients (10.4 ± 5.6 y) with confirmed (39%) or assumed (61%) MFS. Every patient was examined with standardized diagnostic program. Mutation analysis was done in 91% (92/101) of patients with confirmed MFS.

Results: Detection rate of FBN1 was 74.7%. In detail genetic analysis showed missense- (n=32), splicing- (n=11), frameshift- (n=9), nonsense- (n=5) and in-frame-mutations (n=3). Comparison of cardiac pathologies in specific types of mutation did not show a significant difference concerning prevalence and age of manifestation (Table 1).

Prevalence and age of manifestation of dilatation of sinus of valsalvae (SV) or pulmonary artery (PA), mitral valve prolapse (MVP) or regurgation (MVR), tricuspida valve prolapse (TVP), p>0.05

	Frameshift or Nonsense mutation		Splicing mutation		Missense mutation
	Prevalence	Age	Prevalence	Age	Prevalence	Age
SV	83.3%	9.4 ± 1.6 y	81.8%	9.1 ± 2.1 y	62.5%	7.7 ± 1.0 y
PA	33.3%	12.5 ± 2.4 y	18.2%	11.3 ± 4.3 y	50.0%	8.4 ± 1.2 y
MVP	41.7%	11.3 ± 1.2 y	45.5%	6.5 ± 2.4 y	65.6%	7.9 ± 1.2 y
MVR	75.0%	10.6 ± 1.5 y	45.5%	8.9 ± 2.7 y	59.4%	8.6 ± 1.1 y
TVP	75.0%	8.9 ± 1.9 y	36.4%	8.8 ± 3.7 y	71.9%	8.5 ± 1.1 y

Conclusions: Specific type of mutation in FBN1 gene does not correlate with prevalence and age of manifestation of cardiac pathologies in MFS in childhood. Due to age dependent manifestation of symptoms in MFS this could potentially change in older patients. We conclude that in childhood there is no need to differentiate patients with different types of mutation concerning prognosis, follow-up and therapy.