del(17)(p13.3)

Epidemiology and Etiology:

· LIS1 deletion:

· All so far have been de novo

· Isolated lissencephaly sequence (ILS)

· Deletion of adjacent locus or loci in addition to LIS1:

· Miller-Dieker syndrome (MDS)

· Some have been due to a parental rearrangement

· Inversion

· Translocation

· Not necessarily recognizable on karyotype

· Should be very carefully assessed

Common sites:

·

Gross features:

· LIS1 deletion:

· Lissencephaly (“smooth brain”) / agyria / pachygyria (absence / thickness of gyri)

· Radiology can distinguish 17p lissencephaly from X-linked syndrome

· Miller-Dieker:

· More severe brain malformation

· Significant facial dysmorphism

· Other congenital anomalies occasionally:

· Renal

· Gastrointestinal

· cardiac

Histologic features:

·

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

· LIS1 deletion:

· Brain morphogenesis gene

· Results in severe neuronal migration defect

· Deletion may be intragenic or remove the entire gene

· Deletion including LIS1 and adjacent 400 kb “critical region” telomeric to LIS1:

· Miller-Dieker syndrome (MDS)

· Telomeric border of deletion is more distal than in ILS

· eight genes (PRP8, RILP, SREC, PITPNa, SKIP, MYO1C, CRK, and 14-3-3) within this “critical region”

Other features:

· LIS1 deletion:

· Very low recurrence risk (all have been de novo)

References:

· Gardner RJM, Sutherland GR. Chromosome Abnormalities and Genetic Counseling. 2nd ed. Oxford University Press, USA; 1996.

· Am. J. Hum. Genet. 72:918–930, 2003