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Neuropediatrics 2021; 52(03): 227
DOI: 10.1055/s-0040-1722690
Videos and Images in Neuropediatrics

Lissencephaly with Brainstem Hypoplasia and Dysplasia: Think MACF1

Bigna K. Bölsterli 
1   Department of Pediatric Neurology, University Children's Hospital Zurich, Zurich, Switzerland
,
Katharina Steindl
2   Institute of Medical Genetics, University of Zurich, Schlieren-Zurich, Switzerland
,
Raimund Kottke 
3   Department of Diagnostic Imaging, University Children's Hospital Zurich, Zurich, Switzerland
,
Robert Steinfeld 
1   Department of Pediatric Neurology, University Children's Hospital Zurich, Zurich, Switzerland
,
Eugen Boltshauser 
1   Department of Pediatric Neurology, University Children's Hospital Zurich, Zurich, Switzerland
› Author Affiliations Funding None.
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In 2018, Dobyns et al reported de novo MACF1 variants in eight children with a complex brain malformation[1]: diffuse pachygyria with more severe posterior involvement; flat ventral brainstem with - incosistently - a tiny bump on the ventral surface; pontine clefts, and wiede and flat medulla with visible pyramids on the ventral surface. This pattern appeared likely pathognomonic. Clinical features were severe developmental delay, spasticity, and seizures within the first year.

We found this imaging pattern ([Fig. 1]) while reviewing unsolved brainstem malformations in an infant presenting in 2006 with infantile spams and microcephaly. On follow-up, this girl had treatment-resistant epilepsy, severe cognitive impairment, no speech, pronounced spastic cerebral palsy resulting in scoliosis, hip dislocation, and multiple contractures, requiring orthopedic interventions. Swallowing was not impaired. Targeted genetic testing confirmed a pathogenic de novo MACF1 variant [c.15682G>T p.(Asp5228Tyr)]. This observation confirms the value of careful pattern recognition[2] and supports the view that this pattern is likely pathognomonic.

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Fig. 1 MRI (T2-weighted) at 4 months. (A) Sagittal MRI: brainstem hypoplasia, elongated mesencephalon, narrow pons with a tiny bump on the ventral surface (arrow), and thickened medulla. (B) Axial MRI: pachygyria with anterior <posterior gradient. (C) Axial MRI: wide and flat medulla, small pyramids at the ventral surface (arrows). (D) MRI at level of pons: ventral and dorsal clefts (arrows). MRI, magnetic resonance imaging.


Publication History

Received: 11 September 2020

Accepted: 08 October 2020

Article published online:
28 January 2021

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  • References

  • 1 Dobyns WB, Aldinger KA, Ishak GE. et al; University of Washington Center for Mendelian Genomics, Center for Mendelian Genomics at the Broad Institute of MIT and Harvard. MACF1 mutations encoding highly conserved zinc-binding residues of the gar domain cause defects in neuronal migration and axon guidance. Am J Hum Genet 2018; 103 (06) 1009-1021
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  • 2 Rüsch CT, Bölsterli BK, Kottke R, Steinfeld R, Boltshauser E. Pontocerebellar hypoplasia: a pattern recognition approach. Cerebellum 2020; 19 (04) 569-582
    CrossrefPubMedSearch in Google Scholar