Microphthalmia with linear skin defects (MLS) syndrome: clinical, cytogenetic, and molecular characterization

The microphthalmia with linear skin defects (MLS) syndrome (MIM 309801) is a severe developmental disorder observed in XX individuals with distal Xp segmental monosomy. The phenotype of this syndrome overlaps with that of both Aicardi (MIM 304050) and Goltz (MIM 305600) syndromes, two X-linked dominant, male-lethal disorders. Here we report the clinical, cytogenetic, and molecular characterization of 3 patients with this syndrome. Two of these patients are females with a terminal Xpter-p22.2 deletion. One of these 2 patients had an aborted fetus with anencephaly and the same chromosome abnormality. The third patient is an XX male with Xp/Yp exchange spanning the SRY gene which results in distal Xp monosomy. The extensive clinical variability observed in these patients and the results of the molecular analysis suggest that X-inactivation plays an important role in determining the phenotype of the MLS syndrome. We propose that the MLS, Aicardi, and Goltz syndromes are due to the involvement of the same gene(s), and that different patterns of X-inactivation are responsible for the phenotypic differences observed in these 3 disorders. However, we cannot rule out that each component of the MLS phenotype is caused by deletion of a different gene (a contiguous gene syndrome).