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Neuropediatrics 2019; 50(06): 404-405
DOI: 10.1055/s-0039-1688953
Videos and Images in Neuropediatrics
Georg Thieme Verlag KG Stuttgart · New York

VLDLR-associated Pontocerebellar Hypoplasia with Nonprogressive Congenital Ataxia and a Diagnostic Neuroimaging Pattern

Mareike Wilker
1   Department of Pediatric Neurology, Children's Hospital Auf der Bult, Hannover, Germany
,
Hans-Jürgen Christen
1   Department of Pediatric Neurology, Children's Hospital Auf der Bult, Hannover, Germany
,
Sandra Schuster
2   Center for Social Pediatrics and Child Health, Children’s Hospital Auf der Bult, Hannover, Germany
,
Angela Abicht
3   Center of Medical Genetics, Munich, Germany
,
Eugen Boltshauser
4   Department of Pediatric Neurology, University Children's Hospital, Zürich, Switzerland
› Author Affiliations
Further Information

Publication History

12 February 2019

17 March 2019

Publication Date:
01 July 2019 (online)

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Mutations of the very low density lipoprotein receptor (VLDLR) cause severe cerebellar hypoplasia, pontine hypoplasia, and pachygyria (OMIM #224050).[1] Clinically, it leads to nonprogressive congenital ataxia, cognitive impairment, and markedly delayed or absent ambulation. Additional features include pes planus, hyperreflexia, seizures, and short stature.[2] [3] This disorder is inherited in an autosomal recessive fashion.

A 2-year-old boy, second child of consanguineous Iraqi parents, was presented with truncal ataxia and hypotonia; he was unable to stand unaided. He had cognitive and speech delay (spoke only single words) and congenital esotropia ([Video 1]). Formal developmental testing was not performed; the estimated developmental age was less than 18 months. Overall he made developmental progress. Cranial magnetic resonance imaging (MRI; [Fig. 1A–D]) showed pontine hypoplasia, severe cerebellar hypoplasia, lack of vermis foliation, and frontotemporal pachygyria, a constellation unique to VLDLR-associated disorder. Multigene panel analysis confirmed a homozygous c1553T > C variant of VLDLR. This specific variant is not described in literature before. Nevertheless, in view of the overall context a pathogenic effect is most likely.

Video 1

3 years old patient crawling, getting up to stand by holding on examination table and grabbing a doll. Movement pattern shows truncal ataxia and global hypotonia. Patient has a congenital esotropia.


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Fig. 1 (A) Sagittal T1 magnetic resonance image (MRI) of the patient at the age of 2 years 7 months revealing reduced pontine dimension (prominence and cranio-caudal length) and marked hypoplasia of the vermis without foliation. (B) Sagittal T1 MRI of a 3-year-old neurologically normal child for comparison: normal proportion of pontine prominence and normal size of vermis with foliation is evident. (C) Coronal T2 MRI showing marked hypoplasia of cerebellar vermis and hemispheres. (D) Axial T2 MRI demonstrating lack of gyration of both temporal lobes.

This observation underlines the importance of clinical examination, MRI pattern recognition, and targeted genetic analysis to confirm a rare form of congenital ataxia.

 

  • References

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