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Abstract: Congenital Cataracts with Facial Dysmorphisms and Neuropathy (CCFDN) is a complex autosomal recessive disorder characterized by bilateral congenital cataracts, developmental delay, peripheral; hypo-demyelinating neuropathy, mild facial dysmorphisms, and other rare signs. Cerebral and spinal cord atrophy is the main neuroimaging finding but other less common abnormalities have been previously described. We describe progressive focal lesions of supratentorial white matter in a 10-year-old boy affected by CCFDN. Other etiologies have been excluded and these lesions can be considered a new finding of the disease. We discuss a possible demyelinating mechanism affecting both peripheral and central myelin. [Copyright &y& Elsevier]

FHL1 is a member of the four-and-a half-LIM (FHL) domain protein family and it is highly expressed in adult human skeletal muscle. It is believed to participate in sarcomere assembly, muscle growth and differentiation, and in the biomechanical stress responses. Mutations in FHL1 gene have been associated with different myopathies, including reducing body myopathy, scapuloperoneal (SP) myopathy, X-linked myopathy with postural muscle atrophy, rigid spine syndrome (RSS), and Emery-Dreifuss muscular dystrophy. In 2008, we identified a missense mutation in the second LIM domain of FHL1 (c.365 G>C, p.W122S) in a family with SP myopathy. We have generated a knock-in mouse model harboring the c.365 G>C Fhl1 mutation and have investigated the effects of this mutation at pre-symptomatic, phenotypic-onset, and late-stage of the disease, in hemizygous males and heterozygous females mice. Survival was comparable in mutant and wild-type animals. Adult hemizygous males mice showed a slowly progressive phenotype similar to human patients with relatively late-onset muscle weakness. In particular, we observed reduced forelimb strength and exercise capacity. Western blot analysis showed absence of FHL1 protein in muscle of hemizygous males at advanced stages. This animal model may help to elucidate the role of FHL1 in skeletal muscle and the pathomechanism of FHL1 mutations in X-linked dominant scapuloperoneal myopathy. [Copyright &y& Elsevier]