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BMC Pediatrics
Published in: BMC Pediatrics 1/2023

Open Access 01-12-2023 | Epilepsy | Case report

Periventricular nodular heterotopias is associated with mutation at the FLNA locus-a case history and a literature review

Authors: Lin Yang, GuangSheng Wu, HuiMei Yin, MengLan Pan, YaFei Zhu

Published in: BMC Pediatrics | Issue 1/2023

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Abstract

Background

Periventricular nodular heterotopia (PNH), associated with FLNA mutations, is a rare clinical condition potentially associated with multiple systemic conditions, including cardiac, pulmonary, skeletal, and cutaneous diseases. However, due to a paucity of information in the literature, accurate prognostic advice cannot be provided to patients with the disease.

Case presentation

We report a 2-year-old female whose PNH was associated with a nonsense mutation in the q28 region of the X chromosome, in exon 31 of FLNA (c.5159dupA). The patient is currently seizure-free and has no congenital heart disease, lung disease or skeletal or joint issues, and her development is normal.

Conclusions

FLNA-associated PNH is a genetically-heterogeneous disease, and the FLNA mutation, c.5159dupA (p.Tyr1720*) is a newly identified pathogenic variant. FLNA characterization will help the clinical diagnosis and treatment of PNH and provide individualized genetic counseling for patients.
Literature
1.
Vriend I, Oegema R. Genetic causes underlying grey matter heterotopia. Eur J Paediatr Neurol. 2021;35:82–92.CrossRefPubMed
2.
Hiromoto Y, Azuma Y, Suzuki Y, et al. Hemizygous FLNA variant in West syndrome without periventricular nodular heterotopia. Hum Genome Var. 2020;7(1):43.CrossRefPubMedPubMedCentral
3.
Jenkins ZA, Macharg A, Chang CY, et al. Differential regulation of two FLNA transcripts explains some of the phenotypic heterogeneity in the loss-of-function filaminopathies. Hum Mutat. 2018;39(1):103–13.CrossRefPubMed
4.
Wade EM, Halliday BJ, Jenkins ZA, O’Neill AC, Robertson SP. The X-linked filaminopathies: synergistic insights from clinical and molecular analysis. Hum Mutat. 2020;41(5):865–83.CrossRefPubMed
5.
Broix L, Jagline H, Ivanova E, et al. Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia. Nat Genet. 2016;48(11):1349–58.CrossRefPubMedPubMedCentral
6.
Liu W, An D, Niu R, Gong Q, Zhou D. Integrity of the corpus callosum in patients with periventricular nodular heterotopia related epilepsy by FLNA mutation. Neuroimage Clin. 2018;17:109–14.CrossRefPubMed
7.
Parrini E, Ramazzotti A, Dobyns WB, et al. Periventricular heterotopia: phenotypic heterogeneity and correlation with Filamin A mutations. Brain. 2006;129(Pt 7):1892–906.CrossRefPubMed
8.
Meliota G, Vairo U, Ficarella R, Milella L, Faienza MF, D’Amato G. Cardiovascular, brain, and lung involvement in a newborn with a novel FLNA mutation: a case report and literature review. Adv Neonatal Care. 2022;22(2):125–31.
9.
Fergelot P, Coupry I, Rooryck C, et al. Atypical male and female presentations of FLNA-related periventricular nodular heterotopia. Eur J Med Genet. 2012;55(5):313–8.CrossRefPubMed
10.
Parrini E, Mei D, Pisanti MA, et al. Familial periventricular nodular heterotopia, epilepsy and Melnick-Needles Syndrome caused by a single FLNA mutation with combined gain-of-function and loss-of-function effects. J Med Genet. 2015;52(6):405–12.CrossRefPubMed
11.
Zenker M, Rauch A, Winterpacht A, et al. A dual phenotype of periventricular nodular heterotopia and frontometaphyseal dysplasia in one patient caused by a single FLNA mutation leading to two functionally different aberrant transcripts. Am J Hum Genet. 2004;74(4):731–7.CrossRefPubMedPubMedCentral
12.
Tsuneda SS, Torres FR, Montenegro MA, Guerreiro MM, Cendes F, Lopes-Cendes I. A new missense mutation found in the FLNA gene in a family with bilateral periventricular nodular heterotopia (BPNH) alters the splicing process. J Mol Neurosci. 2008;35(2):195–200.CrossRefPubMed
13.
van Kogelenberg M, Clark AR, Jenkins Z, et al. Diverse phenotypic consequences of mutations affecting the C-terminus of FLNA. J Mol Med (Berl). 2015;93(7):773–82.CrossRefPubMed
14.
Hehr U, Hehr A, Uyanik G, Phelan E, Winkler J, Reardon W. A filamin A splice mutation resulting in a syndrome of facial dysmorphism, periventricular nodular heterotopia, and severe constipation reminiscent of cerebro-fronto-facial syndrome. J Med Genet. 2006;43(6):541–4.CrossRefPubMed
15.
Oegema R, Hulst JM, Theuns-Valks SD, et al. Novel no-stop FLNA mutation causes multi-organ involvement in males. Am J Med Genet A. 2013;161A(9):2376–84.CrossRefPubMed
16.
17.
Kasper BS, Kurzbuch K, Chang BS, et al. Paternal inheritance of classic X-linked bilateral periventricular nodular heterotopia. Am J Med Genet A. 2013;161A(6):1323–8.CrossRefPubMed
18.
Moro F, Carrozzo R, Veggiotti P, et al. Familial periventricular heterotopia: missense and distal truncating mutations of the FLN1 gene. Neurology. 2002;58(6):916–21.CrossRefPubMed
19.
de Wit MC, Tiddens HA, de Coo IF, Mancini GM. Lung disease in FLNA mutation: confirmatory report. Eur J Med Genet. 2011;54(3):299–300.CrossRefPubMed
20.
Lord A, Shapiro AJ, Saint-Martin C, Claveau M, Melançon S, Wintermark P. Filamin A mutation may be associated with diffuse lung disease mimicking bronchopulmonary dysplasia in premature newborns. Respir Care. 2014;59(11):e171-7.CrossRefPubMed
21.
Hommel AL, Jewett T, Mortenson M, Caress JB. Juvenile muscular atrophy of the distal upper extremities associated with x-linked periventricular heterotopia with features of Ehlers-Danlos syndrome. Muscle Nerve. 2016;54(4):794–7.CrossRefPubMed
22.
Reinstein E, Chang BS, Robertson SP, Rimoin DL, Katzir T. Filamin A mutation associated with normal reading skills and dyslexia in a family with periventricular heterotopia. Am J Med Genet A. 2012;158A(8):1897–901.CrossRefPubMed
23.
Sheen VL, Jansen A, Chen MH, et al. Filamin A mutations cause periventricular heterotopia with Ehlers-Danlos syndrome. Neurology. 2005;64(2):254–62.CrossRefPubMed
24.
Guerrini R, Mei D, Sisodiya S, et al. Germline and mosaic mutations of FLN1 in men with periventricular heterotopia. Neurology. 2004;63(1):51–6.CrossRefPubMed
25.
Parrini E, Mei D, Wright M, Dorn T, Guerrini R. Mosaic mutations of the FLN1 gene cause a mild phenotype in patients with periventricular heterotopia. Neurogenetics. 2004;5(3):191–6.CrossRefPubMed
26.
de Wit MC, de Coo IF, Lequin MH, Halley DJ, Roos-Hesselink JW, Mancini GM. Combined cardiological and neurological abnormalities due to filamin A gene mutation. Clin Res Cardiol. 2011;100(1):45–50.CrossRefPubMed
27.
Guglielmi V, Floris R, D’Adamo M, Garaci F, Novelli G, Sbraccia P. Massive obesity and hyperphagia in posterior bilateral periventricular heterotopias: case report. BMC Med Genet. 2016;17:18.CrossRefPubMedPubMedCentral
28.
Kinane TB, Lin AE, Lahoud-Rahme M, Westra SJ, Mark EJ. Case 4-2017. A 2-Month-Old girl with growth retardation and respiratory failure. N Engl J Med. 2017;376(6):562–74.CrossRefPubMed
29.
Mercer CL, Andreoletti G, Carroll A, Salmon AP, Temple IK, Ennis S. Familial Ebstein Anomaly: whole exome sequencing identifies novel phenotype Associated with FLNA. Circ Cardiovasc Genet. 2017;10(6):e001683.CrossRefPubMed
30.
Riccio MP, D’Andrea G, Sarnataro E, Marino M, Bravaccio C, Albert U. Bipolar disorder with Melnick-Needles syndrome and periventricular nodular heterotopia: two case reports and a review of the literature. J Med Case Rep. 2021;15(1):495.CrossRefPubMedPubMedCentral
31.
El Chehadeh S, Faivre L, Mosca-Boidron AL, et al. Large national series of patients with Xq28 duplication involving MECP2: delineation of brain MRI abnormalities in 30 affected patients. Am J Med Genet A. 2016;170A(1):116–29.CrossRefPubMed
32.
33.
Arya R, Spaeth C, Zhang W. Epilepsy phenotypes associated with MAP1B-related brain malformations. Epileptic Disord. 2021;23(2):392–6.CrossRefPubMed
34.
Fallil Z, Pardoe H, Bachman R, et al. Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy. Epilepsy Behav. 2015;51:321–7.CrossRefPubMedPubMedCentral
35.
Moutton S, Fergelot P, Naudion S, et al. Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum. J Hum Genet. 2016;61(8):693–9.CrossRefPubMed
36.
Dissanayake R, Senanayake MP, Fernando J, Robertson SP, Dissanayake V, Sirisena ND. Frontometaphyseal dysplasia 1 in a patient from Sri Lanka. Am J Med Genet A. 2021;185(4):1317–20.CrossRefPubMed
Metadata
Title
Periventricular nodular heterotopias is associated with mutation at the FLNA locus-a case history and a literature review
Authors
Lin Yang
GuangSheng Wu
HuiMei Yin
MengLan Pan
YaFei Zhu
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2023
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-023-04161-4

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