Structural brain abnormalities in Pallister-Killian syndrome: a neuroimaging study of 31 children

Abstract

Background: Pallister-Killian syndrome (PKS) is a rare genetic disorder caused by mosaic tetrasomy of 12p with wide neurological involvement. Intellectual disability, developmental delay, behavioral problems, epilepsy, sleep disturbances, and brain malformations have been described in most individuals, with a broad phenotypic spectrum. This observational study, conducted through brain MRI scan analysis on a cohort of patients with genetically confirmed PKS, aims to systematically investigate the neuroradiological features of this syndrome and identify the possible existence of a typical pattern. Moreover, a literature review differentiating the different types of neuroimaging data was conducted for comparison with our population.

Results: Thirty-one individuals were enrolled (17 females/14 males; age range 0.1-17.5 years old at first MRI). An experienced pediatric neuroradiologist reviewed brain MRIs, blindly to clinical data. Brain abnormalities were observed in all but one individual (compared to the 34% frequency found in the literature review). Corpus callosum abnormalities were found in 20/30 (67%) patients: 6 had callosal hypoplasia; 8 had global hypoplasia with hypoplastic splenium; 4 had only hypoplastic splenium; and 2 had a thin corpus callosum. Cerebral hypoplasia/atrophy was found in 23/31 (74%) and ventriculomegaly in 20/31 (65%). Other frequent features were the enlargement of the cisterna magna in 15/30 (50%) and polymicrogyria in 14/29 (48%). Conversely, the frequency of the latter was found to be 4% from the literature review. Notably, in our population, polymicrogyria was in the perisylvian area in all 14 cases, and it was bilateral in 10/14.

Conclusions: Brain abnormalities are very common in PKS and occur much more frequently than previously reported. Bilateral perisylvian polymicrogyria was a main aspect of our population. Our findings provide an additional tool for early diagnosis.Further studies to investigate the possible correlations with both genotype and phenotype may help to define the etiopathogenesis of the neurologic phenotype of this syndrome.

Fig. 1

Brain Trophism and Ventricular System. A, Regular volume of the ventricular system with a slight widening of the peri-cerebral subarachnoid spaces (Case 18, 2 years old); B, mild enlargement of the lateral ventricles and of the peri-cerebral subarachnoid spaces (Case 22, 4 years old); C, more prominent ventriculomegaly and dilatation of the peri-cerebral subarachnoid spaces (Case 11, 1 year old); D, communicating hydrocephalus, with signs of hyperdynamic flow (flow-related artifact on coronal FLAIR on the right) (Case 31, 17 years old)

Fig. 2

Corpus Callosum Morphology.A, Thinning and bowing due to communicating hydrocephalus (Case 9). B, hypoplasia of the corpus callosum, more evident at the splenium (Case 16); C, hypoplasia of the splenium with regular biometry of the other component of the corpus callosum (Case 29); D, global and harmonic hypoplasia of the corpus callosum (Case 31)

Fig. 3

Corpus Callosum Biometry. The figure shows the distribution of biometric data in the analyzed population with respect to age reference percentiles. LCC: length of corpus callosum (curvilinear distance between the rostrum and the splenium at the mid-thickness of the corpus callosum); APD: anteroposterior diameter (distance between the anterior aspect of the genu and the posterior aspect of the splenium)

Fig. 4

Perisylvian Polymicrogyria. A, Bilateral perisylvian polymicrogyria (Case 6); B, bilateral perisylvian polymicrogyria (Case 2); C, right perisylvian polymicrogyria (Case 7); D, left perisylvian polymicrogyria (yellow arrow) and right ischemic clastic perisylvian lesion (white arrow) (Case 26); E, left perisylvian polymicrogyria (yellow arrow) and monomorphic gyri related to dysgiric cortex in the left parietal-temporal-occipital lobe (Case 28); F, bilateral perisylvian polymicrogyria (Case 22); G, bilateral perisylvian polymicrogyria (Case 16); H, bilateral polymicrogyria (Case 24), more evident on the left side; I, bilateral polymicrogyria (Case 19); L, bilateral polymicrogyria (Case 31); M, left perisylvian polymicrogyria (yellow arrow) (Case 5); N, right perisylvian polymicrogyria (yellow arrow) (Case 3); O, right perisylvian polymicrogyria (yellow arrow) and left ischemic clastic perisylvian lesion (white arrow) (Case 17)

Fig. 5

Literature Review Flowchart. PKS: Pallister Killian syndrome; SBAs: structural brain abnormalities; MRI: magnetic resonance imaging; CT: computer tomography; US: ultrasound