Korean J Lab Med.  2011 Jan;31(1):49-53. 10.3343/kjlm.2011.31.1.49.

Miller-Dieker Syndrome with der(17)t(12;17)(q24.33;p13.3)pat Presenting with a Potential Risk of Mis-identification as a de novo Submicroscopic Deletion of 17p13.3

• Kim YJ
• Byun SY
• Jo SA
• Shin YB
• Cho EH
• Lee EY
• Hwang SH

• KMID: 1096661
• DOI: http://doi.org/10.3343/kjlm.2011.31.1.49

Abstract

Miller-Dieker syndrome involves a severe type of lissencephaly, which is caused by defects in the lissencephaly gene (LIS1). We report the case of a female infant with der(17)t(12;17)(q24.33;p13.3)pat caused by an unbalanced segregation of the parental balanced translocation of 17p with other chromosomes. The proband presented with facial dysmorphism, arthrogryposis, and intrauterine growth retardation. Most cases of Miller-Dieker syndrome have a de novo deletion involving 17p13.3. When Miller-Dieker syndrome is caused by an unbalanced translocation, mild-to-severe phenotypes occur according to the extension of the involved partner chromosome. However, a pure partial monosomy derived from a paternal balanced translocation is relatively rare. In this case, the submicroscopic cryptic deletion in the proband was initially elucidated by FISH, and karyotype analysis did not reveal additional chromosome abnormalities such as translocation. However, a family history of recurrent pregnancy abnormalities strongly suggested familial translocation. Sequential G-banding and FISH analysis of the father's chromosomes showed that the segment of 17p13.3-->pter was attached to the 12qter. Thus, we report a case that showed resemblance to the findings in cases of a nearly pure 17p deletion, derived from t(12;17), and delineated by whole genome array comparative genomic hybridization (CGH). If such cases are incorrectly diagnosed as Miller-Dieker syndrome caused by de novo 17p13.3 deletion, the resultant improper genetic counseling may make it difficult to exactly predict the potential risk of recurrent lissencephaly for successive pregnancies.

Keyword

Miller-Dieker syndrome; Lissencephaly; Array comparative genomic hybridization; Partial monosomy 17p

MeSH Terms

Abnormalities, Multiple/genetics
Adult
Brain/abnormalities
Chromosome Banding
Chromosome Segregation
*Chromosomes, Human, Pair 12
*Chromosomes, Human, Pair 17
Classical Lissencephalies and Subcortical Band Heterotopias/*diagnosis
Female
Gene Deletion
Humans
In Situ Hybridization, Fluorescence
Infant, Newborn
Karyotyping
Magnetic Resonance Imaging
Male
Phenotype
Risk
Translocation, Genetic

Figure

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  Fig. 1 T2-weighted brain magnetic resonance imaging showing lissencephaly with band heterotopia and agenesis of the corpus callosum.

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  Fig. 2 (A) Results of presumptive karyotype analysis of the proband [46,XX,del(17)(p13)] showing deletion of 17p.13→pter (arrow). (B) Results of presumptive karyotype analysis of the proband's father [46,XY,t(12;17)(q24.33;p13)].

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  Fig. 3 (A) Proband's metaphase FISH results. One orange and 2 green signals indicate loss of 17p13.3. (B) Sequential G-banding (left) and FISH (right) performed on her father's metaphase chromosomes. G-banded metaphase with arrows indicating chromosome 12 and 17. Note that an orange signal of 17p13.3 is observed in chromosome 12q.

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  Fig. 4 Array comparative genomic hybridization ratio profile data for chromosomes 12 and 17 of the proband. Chromosome 12 shows no duplication or deletion on the q-arm (left). Chromosome 17 shows deletion (-4.6 Mb) on the p-arm (right).

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