Miller-Dieker Syndrome, 17p13.3 Deletion, FISH
Aids in the diagnosis of 17p13.3 deletion (Miller-Dieker syndrome or type I lissencephaly), in conjunction with high-resolution chromosome studies (CMS / Chromosome Analysis, for Congenital Disorders, Blood)
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Miller-Dieker syndrome is associated with a deletion on the short arm of chromosome 17. The syndrome can be suspected in patients with microcephaly and a prominent forehead with vertical skin furrowing and bitemporal narrowing. The phenotype includes type I lissencephaly (cerebral agyria or smooth brain with a 4-layer cortex), profound electroencephalogram (EEG) abnormality, seizures, hypotonia, severe-to-profound mental retardation, and pre- and postnatal growth retardation. Facial features include ptosis (droopy eyelid), upturned nares, long philtrum (vertical groove on the midline of the upper lip) with thin upper lip, mild micrognathia (small jaw), and malformed ears. Heart and kidney defects are common. Most patients die in infancy.
High-resolution chromosome studies (CMS / Chromosome Analysis, for Congenital Disorders, Blood) are recommended for patients suspected of having Miller-Dieker syndrome to detect the deletion and to rule out other chromosome abnormalities or translocations. FISH studies are also recommended to detect cryptic translocations involving 17p13.3 that are not demonstrated by conventional chromosome studies.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Any individual with a normal signal pattern (2 signals) in each metaphase is considered negative for a deletion in the region tested by this probe.
Any patient with a FISH signal pattern indicating loss of the critical region will be reported as having a deletion of the regions tested by this probe. This is consistent with a diagnosis of 17p13.3 deletion (Miller-Dieker syndrome or type 1 lissencephaly).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Because this FISH test is not approved by the FDA, it is important to confirm Miller-Dieker syndrome or type I lissencephaly diagnoses by other established methods, such as clinical history or physical examination.
This FISH analysis identified a deletion in 4 patients with a phenotype consistent with Miller-Dieker syndrome or a cytogenetic or telomere 17p deletion. Four additional patients with chromosome anomalies involving chromosome 17, but not the 17p13.3 deletion, were further characterized using this probe set. This demonstrated this probe’s ability to define other chromosome 17 rearrangements in this region that are not consistent with 17p13.3 deletion.
No deletions of the Miller-Dieker critical region were identified in 20 patient specimens from peripheral blood, tissue, or amniotic fluid with a normal karyotype or FISH telomere analysis results.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Van Dyke DL, Wiktor A: Chapter 26: Clinical cytogenetics. In Laboratory Medicine. Second edition. Edited by K McClatchey. Baltimore, Williams and Wilkins, 2002
2. Jones K: Miller-Dieker syndrome (Lissencephaly syndrome). In Smith's Recognizable Patterns of Human Malformation. Fifth edition. Philadelphia, WB Saunders Company, 1997
3. Cardoso C, Leventer RJ, Ward HL, et al: Refinement of a 400 kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3. Am J Hum Genet 2003;72:918-930