Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jul 13;6(4):e482.
doi: 10.1212/NXG.0000000000000482. eCollection 2020 Aug.

Hydrocephalus and diffuse choroid plexus hyperplasia in primary ciliary dyskinesia-related MCIDAS mutation

Evie Alexandra Robson  1 , Luke Dixon  1 , Liam Causon  1 , William Dawes  1 , Massimo Benenati  1 , Mahmoud Fassad  1 , Robert Anthony Hirst  1 , Priti Kenia  1 , Eduardo Fernandez Moya  1 , Mitali Patel  1 , Daniel Peckham  1 , Andrew Rutman  1 , Hannah M Mitchison  1 , Kshitij Mankad  1 , Christopher O'Callaghan  1
Affiliations

Hydrocephalus and diffuse choroid plexus hyperplasia in primary ciliary dyskinesia-related MCIDAS mutation

Evie Alexandra Robson et al. Neurol Genet. .

Abstract

Objective: To report a neuroradiologic phenotype associated with reduced generation of multiple motile cilia (RGMC) and mutations in the multicilin gene. We hypothesize that the observed phenotype may reflect the emerging role that ependymal cilia play in regulating CSF production.

Method: Clinical and radiologic records were retrospectively reviewed for 7 consecutive patients diagnosed by the Leicester UK national primary ciliary dyskinesia (PCD) diagnostic laboratory.

Results: On MRI scanning, all patients demonstrated hydrocephalus, choroid plexus hyperplasia (CPH), and arachnoid cysts. No patient had any sign of neurologic deficit. All patients had significant lung disease.

Conclusions: We conclude that there is a high incidence of hydrocephalus, arachnoid cysts, and CPH in MCIDAS-associated RGMC. In all cases, the observed hydrocephalus seems arrested in childhood without progression or adverse neurologic sequelae. Our new observation of CPH, which is associated with CSF overproduction, is the first macroscopic evidence that ependymal cilia may be involved in the regulation of CSF production and flow. We suggest that brain imaging should be performed in all cases of RGMC and that a diagnosis of PCD or RGMC be strongly considered in patients with unexplained hydrocephalus and a lifelong "wet"-sounding cough.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Selection of images from the full study cohort
Images A, C, and E correspond with patient D; D and F, with patient G; and B, with patient F. Note (A) [axial FLAIR] and (B) [axial T1-WI] on different patients showing choroid plexus hyperplasia (arrows). High-resolution sagittal T2-WI (D, E) confirming CSF flow through the aqueduct of Sylvius (arrowheads) and large retro cerebellar arachnoid cyst in both cases (stars). Further arachnoid cysts were noted in other locations as shown in C (axial T2-WI) and F (axial FLAIR) within the anterior and middle cranial fossae respectively (stars).
Figure 2
Figure 2. Familial segregation of MCIDAS mutations detected in reduced generation of multiple motile cilia families
Mutations were identified by next-generation gene panel sequencing of family members. The sequences of a carrier parent (top) and affected child (bottom) are shown for pedigree of C, D, E, F and G with the mutation highlighted in the box. Sequences for A and B were reported previously.,
See this image and copyright information in PMC

References

    1. Chilvers MA, O'Callaghan C. Analysis of ciliary beat pattern and beat frequency using digital high speed imaging: comparison with the photomultiplier and photodiode methods . Thorax 2000;55:314–317. - PMC - PubMed
    1. Ibanez-Tallon I, Pagenstecher A, Fliegauf M, et al. . Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation . Hum Mol Genet 2004;13:2133–2141. - PubMed
    1. Vieira JP, Lopes P, Silva R, Primary ciliary dyskinesia and hydrocephalus with aqueductal stenosis . J Child Neurol 2012;27:938–941. - PubMed
    1. Boon M, Wallmeier J, Ma L, et al. . MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia . Nat Commun 2014;5:4418. - PubMed
    1. Wallmeier J, Al-Mutairi DA, Chen CT, et al. . Mutations in CCNO result in congenital mucociliary clearance disorder with reduced generation of multiple motile cilia . Nat Genet 2014;46:646–651. - PubMed