Abstract
The Miller-Dieker syndrome (MDS) is a severe neurological disorder characterized by lissencephaly, facial dysmorphies, global developmental delay and severe seizures. A deletion at 17p13.3, including the lissencephaly gene (LIS1), is usually present as part of a contiguous gene syndrome. Around 20% of case LSI1 gene is resulting from inherited balanced translocation. We present the case of a family with cryptic t(12;17) translocation identified by FISH in two generations. The proband had clinical features of MDS. The parents reported a paternal aunt deceased as a young infant due to “uncontrolled seizures and severe developmental delay. The GTG analysis of proband suggested deletion at 17p13.3 that was confirmed by FISH. The parental investigation by FISH revealed a paternal translocation involving regions 12qter and 17p13.3. This familial chromosomal rearrangement associated to MDS has modified the genetic counseling of the couple. From a very low risk of recurrence on the cases associated to a <i>de novo</i> del17p13.3, to a much higher risk, since it was associated to a familial translocation. This risk of recurrence, considering meiotic segregation of balanced translocation involving the 17p13.3 region is relatively high (12%) which alone would justify prenatal diagnosis. Classical and molecular cytogenetic investigations in the fetal sample were normal reassuring the couple as to a normal baby with neither 17p13.3 deletion nor carrier of the paternal translocation. This rare case identified by FISH demonstrate the need of providing molecular cytogenetic analysis for other family members; since, criptical balanced rearrangements may segregate undetected. This case evidences the importance of molecular study of parents of children with microdeletions, which could considerably improve the certainties regarding genetic counseling.
Highlights
Miller-Dieker syndrome (MDS), or chromosome 17p13.3 deletion syndrome is characterized by classic lissencephaly, microcephaly, wrinkled skin over the glabella and frontal suture, prominent occiput, narrow forehead, downward slanting palpebral fissures, small nose and chin, growth retardation, and mental deficiency with severe seizures and EEG abnormalities
The major facial anomalies typical of MDS are presumed to result from deletion of additional genes 200–300 kb telomeric to this locus [2, 3], 51 Elenice Ferreira Bastos et al.: Inherited Cryptic Translocation t(12;17)(q24.3;p13.3) Causing Recurrence of Miller-Dieker Syndrome characterizing an example of contiguous gene syndrome
(LIS) is characterized by a smooth or nearly smooth brain surface and a shortage of gyrus and sulcal development, encompassing a spectrum of malformations of the brain surface ranging from complete agyria to subcortical band heterotopia (SBH) [1]
Summary
Miller-Dieker syndrome (MDS), or chromosome 17p13.3 deletion syndrome is characterized by classic lissencephaly, microcephaly, wrinkled skin over the glabella and frontal suture, prominent occiput, narrow forehead, downward slanting palpebral fissures, small nose and chin, growth retardation, and mental deficiency with severe seizures and EEG abnormalities. The major facial anomalies typical of MDS are presumed to result from deletion of additional genes 200–300 kb telomeric to this locus [2, 3], 51 Elenice Ferreira Bastos et al.: Inherited Cryptic Translocation t(12;17)(q24.3;p13.3) Causing Recurrence of Miller-Dieker Syndrome characterizing an example of contiguous gene syndrome. About 90% of MDS cases have a visible chromosomal deletion at 17p13.3. These deletions are submicroscopic only detect by in situ hibridization [4]
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