BACKGROUND: Deletions in the 17p13.3 region are associated with abnormal 
neuronal migration. Point mutations or deletion copy number variants of the 
PAFAH1B1 gene in this genomic region cause lissencephaly, whereas extended 
deletions involving both PAFAH1B1 and YWHAE result in Miller-Dieker syndrome 
characterised by facial dysmorphisms and a more severe grade of lissencephaly. 
The phenotypic consequences of YWHAE deletion without deletion of PAFAH1B1 have 
not been studied systematically.
METHODS: We performed a detailed clinical and molecular characterization of five 
patients with deletions involving YWHAE but not PAFAH1B1, two with deletion 
including PAFAH1B1 but not YWHAE, and one with deletion of YWHAE and mosaic for 
deletion of PAFAH1B1.
RESULTS: Three deletions were terminal whereas five were interstitial. Patients 
with deletions including YWHAE but not PAFAH1B1 presented with significant 
growth restriction, cognitive impairment, shared craniofacial features, and 
variable structural abnormalities of the brain. Growth restriction was not 
observed in one patient with deletion of YWHAE and TUSC5, implying that other 
genes in the region may have a role in regulation of growth with CRK being the 
most likely candidate. Using array based comparative genomic hybridisation and 
long range polymerase chain reaction, we have delineated the breakpoints of 
these nonrecurrent deletions and show that the interstitial genomic 
rearrangements are likely generated by diverse mechanisms, including the 
recently described Fork Stalling and Template Switching (FoSTeS)/Microhomology 
Mediated Break Induced Replication (MMBIR).
CONCLUSIONS: Microdeletions of chromosome 17p13.3 involving YWHAE present with 
growth restriction, craniofacial dysmorphisms, structural abnormalities of brain 
and cognitive impairment. The interstitial deletions are mediated by diverse 
molecular mechanisms.