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The Marfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue. Variable and pleiotropic clinical features are observed in the skeletal, ocular, and cardiovascular systems. The most severe end of the phenotypic spectrum of this disorder comprises a group of patients usually diagnosed at birth, who have a life expectancy of little more than a year. To distinguish this group of patients from those with classical MFS, we refer to them as neonatal Marfan syndrome (nMFS). These infants usually die of congestive heart failure rather than aortic aneurysmal disease, the most frequent cause of morbidity and mortality in classical MFS. Defects in fibrillin, an elastin-associated microfibrillar glycoprotein, are now known to cause both the classical and neonatal forms of MFS. Here we report the recurrent mis-splicing of fibrillin (FBN1) exon 32, a precursor EGF-like calcium binding domain, in two unrelated infants with nMFS. The mis-splicing, in one patient, was due to an A-->T transversion at the -2 position of the consensus acceptor splice site; while that in the second patient was caused by a G-->A transition at the +1 position of the donor splice site. Characterization of FBN1 mutations in individuals at the most severe end of the Marfan syndrome spectrum should provide greater understanding of the multiple domains and regions of fibrillin.

A 4-year-old girl with the Marshall-Smith syndrome (MSS) is described. A muscle biopsy was performed because of hypotonia and muscular weakness. Selective hypoplasia of type IIa and IIb fibers was found. Additional not previously reported findings in this girl were a partial growth hormone deficiency, a partial villous atrophy of the small bowel and a pronounced dicarboxylic aciduria. The significance of these findings in MSS is not clear and the results of similar investigations in other MSS patients have to be awaited.

Fibromuscular dysplasia of the arteries (FMD) is a segmental angiopathy which may produce obstruction of the carotid, cerebral, renal, mesenteric, coronary or iliac arteries. Except for lesions related to arterial hypertension, retinal manifestations have not yet been reported. This paper describes the case of a 10-year-old boy with progressive deafness, a history of an unexplained stroke and progressive occlusions of the retinal arterioles in the fundus periphery. This resulted in retinal neovascularization and recurrent retinal and vitreous hemorrhages. Despite repeated photo- and cryocoagulation the eyes progressed to a tractional retinal detachment which was successfully treated by vitrectomy and scleral buckling. The diagnosis of FMD was made on the basis of a histopathological examination of a temporal artery biopsy. The child also presented an asymptomatic but severe aneurysmal dilatation of the aorta and CT scan and MRI showed dilated cerebral arteries. The father of our patient had died at the age of 27 years either from myocardial infarction or rupture of a dissecting aortic aneurysm. He was highly myopic and had lost one eye from retinal detachment. The younger brother of our patient also presents aneurysmal dilatation of the aorta and tortuous cerebral vessels. Ocular examination is still normal. The findings in this family are compatible with an autosomal dominant inheritance with variable expression.