A case of FLNA gene mutation with respiratory insufficiency and periventricular heterotopia

Hwanhee Park; Min-Seung Park; Chang-Seok Ki; Joongbum Cho; Jeehun Lee; Jihyun Kim; Kangmo Ahn

doi:10.4168/aard.2019.7.3.158

Journal List > Allergy Asthma Respir Dis > v.7(3) > 1130420

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Park, Park, Ki, Cho, Lee, Kim, and Ahn: A case of FLNA gene mutation with respiratory insufficiency and periventricular heterotopia

Case Report

Allergy Asthma Respir Dis 2019;7(3):158-164.

Published online: 12 July 2019

DOI: https://doi.org/10.4168/aard.2019.7.3.158

A case of FLNA gene mutation with respiratory insufficiency and periventricular heterotopia

Hwanhee Park¹, Min-Seung Park², Chang-Seok Ki², Joongbum Cho¹, Jeehun Lee¹, Jihyun Kim^1,³, Kangmo Ahn^1,³

^¹Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul Korea

^²Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul Korea

^³Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul Korea

Correspondence to: Kangmo Ahn https://orcid.org/0000-0001-7751-9829 Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea Tel: +82-2-3410-3539, Fax: +82-2-3410-0805, E-mail: kmaped@skku.edu

Received 18 April 2018 Revised 24 July 2018 Accepted 24 July 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Filamin A is an actinbinding protein and, in humans, is encoded by FLNA gene in the long arm of X chromosome. Filamin A plays a role in the formation of cytoskeleton by crosslinking actin filaments in cytoplasm. FLNA mutations affect cytoskeletal regulatory processes and cellular migrating abnormalities that result in periventricular heterotopia. A 5-month-old girl was hospitalized because of breathing difficulty and was diagnosed as having periventricular heterotopia with laryngomalacia, cricopharyngeal incoor-dination, pulmonary hypertension, and chronic lung disease. A genetic test was performed to find the cause of periventricular heterotopia, and FLNA gene mutation (c.5998+1G>A) was confirmed for the first time in Korea. After discharge, she developed respiratory failure due to a viral infection at 8 months of her age. In spite of management with mechanical ventilation, she died of pneumothorax and pulmonary hemorrhage. Herein, we report a case of FLNA gene mutation who presented with periventricular nodular heterotopia with respiratory insufficiency.

Keywords: Filamin A, Respiratory insufficiency, Periventricular heterotopia, Korea

References

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Fig. 1.

Chest X-ray of the patient. Anteroposterior view shows atelectasis of both upper lung fields.

Fig. 2.

Chest computed tomography (CT) of the patient. Axial view of upper (A), middle (B), lower (C) zones, and coronal view (D) show hyperinflation in both upper lobes and right middle lobe. Multifocal subsegmental atelectasis is also present in both lower lobes. Narrowing of the both bronchi (arrow heads) suggests bronchomalacia.

Fig. 3.

Brain magnetic resonance image scan of the patient. T1 (A) and T2 (B) axial planes show bilateral periventricular nodular heterotopia.

Fig. 4.

Electropherogram of FLNA gene sequences of the patient and her parents. The patient and her mother are found to have heterozygous mutation of FLNA gene (c.5998+1G>A).

Table 1.

A summary of previous FLNA gene mutation cases

Study	No. of case	Mutation	Sex	Age at presentation	Neurological manifestation	Brain image	Pulmonary manifestation	Chest image (CXR, CT)	Other clinical manifestation	Outcomes
Singh et al.⁶	4	Frameshift (3 patients) Missense (1 patient)	Female (4 patients)	7 Weeks– 4 months	Not stated	Not stated	Progressive respiratory failure	Hyperinflation, emphysema	PDA, ligamentous laxity, strabismus	One patient died of viral pneumonia 8 weeks after 2nd lung transplantation. The remaining patients are thriving and doing well at ages 8 years, 1.7 years, and 5 months after lung transplant.
Masurel-Paulet et al.⁷	1	Mosaic nonsense	Male	3 Months	DD hypotonia	PNH	Tachypnea, tracheobronchomalacia	Atelectasis	Gastrostomy, PDA, AR	Still alive at 6 years of age — requires supplementary oxygen (lobectomy at 8 months of age)
de Wit et al.⁸	1	Missense mutation	Female	3 Months	DD (motor) hypotonia	PNH	Dyspnea, bronchomalacia, respiratory infections	Emphysema	ASD, CoA, mild AR, hyperlaxity	Still alive at 3 years of age (lobectomy at 1 year of age)
Lord et al.⁹	1	Truncating	Female	24 Days	DD (motor) hypotonia	PNH	Tachypnea, tracheobronchomalacia	Hyperinflation, atelectasis, patchy ground-glass		Still alive at 22 months of age — prolonged oxygen dependence
Eltahir et al.¹⁰	1	Pathogenic variant	Female	2 Months	DD, hypotonia	None performed	Recurrent cyanotic events	Hyperinflation, atelectasis	PDA, hyperlaxity GERD	Death at 15 months of age
Shelmerdine et al.¹¹	4	Mutation seen at c.88delG	Female	3 Months	None	Not stated	Difficulty in breath	Hyperinflation, pneumothorax	PDA	Death at 9 months age (from respiratory arrest)
		Mutation seen at c.6496dupA	Female	7 Months	None	PNH	Choking, pulmonary infection	Hyperinflation, atelectasis, patchy ground-glass	PDA	Still alive at 4 years of age (Lobectomy at 1 year of age)
		Mutation seen at c.1528G>A	Female	At birth	None	Not stated	Increased work of breath, bronchomalacia	Hyperinflation, atelectasis		Still alive at 3 years of age — requires bronchodilator inhalers
		Mutation seen at c.2190_2193del TTAC	Female	3 Months	None	Not stated	Viral bronchiolitis	Hyperinflation, atelectasis	ASD, PDA	Still alive at 6 years of age — requires supplementary oxygen, bronchodilator inhalers
Bickel et al.¹²	1	Mutation seen at c.988–1 G>C	Female	Not stated	Seizure	PNH	ILD, pneumothorax, asthma	Hyperinflation, atelectasis, patchy ground-glass		Still alive at 9 years of age

CXR, chest X-ray; CT, computed tomography; DD, developmental delay; PNH, periventricular nodular heterotopia; PDA, patent ductus arteriosus; ASD, Atrial septal defect; CoA, coarctation of the aorta; AR, aortic regurgitation; GERD, gastroesophageal reflux disease; ILD, interstitial lung disease.

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