A review of structural brain abnormalities in Pallister-Killian syndrome

作者：Poulton Cathryn; Baynam Gareth; Yates Clarissa; Alinejad-Rokny Hamid; Williams Simon; Wright Helen; Woodward Karen J.; Sivamoorthy Soruba; Peverall Joanne; Shipman Peter; Ravine David; Beilby John; Heng Julian Ik-Tsen^*

来源：Molecular Genetics & Genomic Medicine, 2018, 6(1): 92-98.

DOI：10.1002/mgg3.351

• corpus callosum
• Pallister-Killian syndrome
• polymicrogyria
• structural brain disorder

Background
Pallister-Killian syndrome (PKS) is a rare multisystem developmental syndrome usually caused by mosaic tetrasomy of chromosome 12p that is known to be associated with neurological defects.
Methods
We describe two patients with PKS, one of whom has bilateral perisylvian polymicrogyria (PMG), the other with macrocephaly, enlarged lateral ventricles and hypogenesis of the corpus callosum. We have also summarized the current literature describing brain abnormalities in PKS.
Results
We reviewed available cases with intracranial scans (n=93) and found a strong association between PKS and structural brain abnormalities (77.41%; 72/93). Notably, ventricular abnormalities (45.83%; 33/72), abnormalities of the corpus callosum (25.00%; 18/72) and cerebral atrophy (29.17%; 21/72) were the most frequently reported, while macrocephaly (12.5%; 9/72) and PMG (4.17%; 3/72) were less frequent. To further understand how 12p genes might be relevant to brain development, we identified 63 genes which are enriched in the nervous system. These genes display distinct temporal as well as region-specific expression in the brain, suggesting specific roles in neurodevelopment and disease. Finally, we utilized these data to define minimal critical regions on 12p and their constituent genes associated with atrophy, abnormalities of the corpus callosum, and macrocephaly in PKS.
Conclusion
Our study reinforces the association between brain abnormalities and PKS, and documents a diverse neurogenetic basis for structural brain abnormalities and impaired function in children diagnosed with this rare disorder.

• 出版日期2018-1