Classical lissencephaly syndromes: does the face reflect the brain?

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Abstract
Both Miller-Dieker syndrome and isolated lissencephaly sequence are associated with classical lissencephaly. Both have been shown to be associated with deletions and mutations in LIS1 on 17p. Traditionally, the two disorders have been distinguished by the presence of a characteristic facial appearance in Miller-Dieker syndrome. The forehead is tall and prominent and may have vertical furrowing. There is narrowing at the temples. Eyes are widely spaced with upward slanting fissures. The nose is very short with anteverted nares. The upper lip is long, wide, and thick. The ears may have minor flattening of the helices. By contrast, these features are not seen in isolated lissencephaly sequence. We have measured five children with Miller-Dieker syndrome (MDS) and 25 children and adolescents with isolated lissencephaly sequence (ILS). Z score (standard deviation score) pattern profiles have been formulated and compared. Patients with ILS at all ages show reduced head circumference, a round head, and a wide and flat face with a broad nose and widely spaced eyes. The most unexpected finding is the similarity of pattern profiles of ILS and MDS in the age group 6 months to 4 years. Correlation coefficient is 0.812 (p<0.001). In MDS there are a few distinguishing features, including brachycephaly, a slightly wider face, and a considerably shorter nose. Given the striking similarity of these objective pattern profiles, it seems likely that the principal diagnostic discriminators are qualitative features, specifically the tall, furrowed forehead and the long, broad, thickened upper lip, which is so thick that the vermilion border of the upper lip is inverted and angled down.