Miller-Dieker syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Miller-Dieker syndrome is a disease characterised by a developmental defect of the brain, caused by incomplete neuronal migration.

Historical Perspective

It is named for JQ Miller^[1] and H. Dieker.^[2]

Pathophysiology

The brain is smooth (also known as lissencephaly), has an absence of sulci and gyri, has a cerebral cortex 4 layers thick instead of 6 and shows microcephaly. There are multiple abnormalities of the brain, heart, kidney and gastrointestinal tract.

Originally thought to be an autosomal recessive disorder, it is now known to be an autosomal dominant disorder, and a haploinsufficiency of one or more genes on chromosome 17p.

The disease arises from the deletion of part of 17p (which includes both the LIS1 and 14-3-3 epsilon gene), leading to partial monosomy. There may be unbalanced translocations (ie 17q:17p or 12q:17p), or the presence of a ring chromosome 17.

Natural History, COmplications, Prognosis=

There is delayed growth and delayed mental development. Death tends to occur in infancy and childhood.

Diagnosis

The disease may be diagnosed by cytogenetic techniques, testing for a microdeletion at LIS1.^[3]

References

↑ Miller JQ (1963). “Lissencephaly in 2 siblings”. Neurology. 13: 841–50. PMID 14066999.
↑ Dieker, H.; Edwards, R. H.; ZuRhein, G. et al. The lissencephaly syndrome.In: Bergsma, D. : The Clinical Delineation of Birth Defects: Malformation Syndromes. New York: National Foundation-March of Dimes (pub.) II 1969. Pp. 53-64.
↑ Izumi K, Kuratsuji G, Ikeda K, Takahashi T, Kosaki K (2007). “Partial deletion of LIS1: a pitfall in molecular diagnosis of Miller-Dieker syndrome”. Pediatr. Neurol. 36 (4): 258–60. doi:10.1016/j.pediatrneurol.2006.11.015. PMID 17437911.

Overview