[Clinical signs of Marfan syndrome in children under 10 years of age]. / Signes cliniques évocateurs d'un syndrome de Marfan chez l'enfant de moins de 10ans.

Diagnosing Marfan syndrome in young children is difficult because of the great variability of expression of the disease and because the phenotype evolves over the life course. The goal of this retrospective study was to describe the first clinical symptoms in children under 10 years of age with Marfan syndrome and to evaluate the pertinence of the new 2010 Ghent criteria in comparison with the 1996 criteria. Seventeen patients under 10 by the time of the first medical examination were included. All children had an FBN1 gene mutation that was secondarily demonstrated. Clinical data including ophthalmological, cardiac, and orthopaedic examinations obtained during the first medical examination were analyzed. The most frequent abnormalities encountered were high arched palate (82%), arachnodactyly (71%), and flatfoot (59%). Aortic aneurysm (47%) and ectopic lens (35%) were also seen at the time of diagnosis. According to the 2010 Ghent criteria, the diagnosis of Marfan syndrome could be obtained in 71% of patients after identification of the mutation of the FBN1 gene, whereas only 59% of patients were diagnosed using the older criteria. All organs can be affected during childhood. An early diagnosis is essential in order to set up specific management.

Arachnodactyly--a key to diagnosing heritable disorders of connective tissue.

Arachnodactyly literally means spidery fingers, and describes the long, slender fingers typical of patients with Marfan syndrome (MFS). Many clinicians regard arachnodactyly as pathognomonic of MFS; however, this view is misleading as arachnodactyly is a key element of the marfanoid habitus, which is present in several heritable disorders of connective tissue (HDCTs). Other features of the marfanoid habitus include long hands and feet, increased skin stretch, joint hypermobility and characteristic changes in the physiology of the pectum. Here, we focus on the differential diagnosis of diseases with features of the marfanoid habitus. Ectopia lentis (lens dislocation) and aortic root dilation or dissection are cardinal features of MFS. Distinguishing MFS from other HCDTs has important implications for treatment, as cardiovascular and ocular complications commonly seen in patients with MFS are not seen in all HDCTs. Joint hypermobility syndrome and Ehlers-Danlos syndrome are also HDCTs, neither of which is associated with ectopia lentis or aortic changes. Some of the rarer forms of Ehlers-Danlos syndrome are associated with severe vascular, dental and skin pathologies. This Review serves as a guide for correctly diagnosing members of the HDCT family.

Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa.

Mutations involving elastic tissue proteins result in a broad spectrum of phenotypes affecting skin, skeleton, ocular and vascular structures, including tortuous blood vessels and cutis laxa. Here we report on a female newborn with apparently long fingers, aortic aneurysm, tortuous pulmonary arteries and mild generalized lax skin. She died at 27 days of age due to severe respiratory distress and inoperable systemic vascular abnormalities. Skin biopsy showed marked paucity and fragmentation of elastic fibers and autopsy revealed occlusion of the pulmonary artery. DNA analysis identified compound heterozygous mutations ((c.835C > T (p.R279C)/c.1070_1073dupCCGC) in fibulin-4, a recently recognized elastic fiber associated protein. Analyses of dermal fibroblasts from the patient indicated that fibulin-4 mRNAs with the 4-bp duplication transcribed from one allele are probably subject to nonsense-mediated decay, whereas synthesis and secretion of the missense R279C fibulin-4 protein from the other allele is severely impaired. Immunostaining demonstrated a total absence of fibulin-4 fibers in the extracellular matrix deposited by the patient's fibroblasts. Our studies provide evidence that deficiency in fibulin-4 leads to a perinatal lethal condition associated with elastic tissue abnormalities.