![]() ![]() She was diagnosed with suspected MFS at birth caused by the presence of finger and toe arachnodactyly, elbow and knee flexion contractures, a characteristic ‘senile’ facial appearance, and loose skin, so was referred to the pediatrician. Her father was 32 years old and her mother 26 years old. ![]() Here, we present a novel missense mutation associated with nMFS, which leads to a cysteine substitution in the calcium-binding epidermal growth factor-like (cbEGF) 12 domain of FBN1.Īn 8-month-old Han Chinese girl, the only child of her parents, was born full-term weighing 2.60 kg by vaginal delivery. In the UMD-FBN1 mutations database ( ), a total of 1,318 different FBN1 mutations for MFS have been included to date, of which only 59 (4.8 %) including 37 missense mutations (2.8 %) are associated with nMFS. NMFS has been correlated with a limited number of mutations in the neonatal region of the fibrillin-1 gene ( FBN1) (OMIM 134797). Valvular insufficiencies and diaphragmatic hernias have been associated with shorter survival in patients diagnosed before the age of 1 year. The prognosis of nMFS is very poor, with a mean survival age of only 16.3 months. MFS patients present with clinical variability, in which the rare neonatal Marfan syndrome (nMFS) has the most severe presentation in early childhood. Marfan syndrome (MFS) (OMIM 154700) is an autosomal dominant disorder of fibrous connective tissue involving the ocular, skeletal, and cardiovascular systems. An analysis of nMFS-associated mutations from the UMD-FBN1 database indicates that those de novo mutations altering disulfide bonds or Ca 2+ binding sites of the cbEGF domains encoded by exons 25–33, and a lack of phenotypic heterogeneity may be associated with an increased risk for nMFS. This variant was absent in 208 ethnically matched controls, providing further evidence that it may be causative of nMFS. The mutation leads to the substitution of a highly conserved FBN1 cysteine residue (p.Cys1111Arg), which is likely to severely perturb the FBN1 structure because of an alteration of the disulfide bond pattern in the calcium-binding epidermal growth factor-like (cbEGF) 12 domain. Genetic analysis revealed that she was heterozygous for a de novo FBN1 missense mutation (c.3331 T > C). An 8-month-old Han Chinese girl presented with the classic nMFS phenotype, including prominent manifestations of bone overgrowth, aortic root dilatation, and multiple cardiac valve dysfunctions. ![]()
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