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КАРДІОЛОГИ, СІМЕЙНІ ЛІКАРІ, РЕВМАТОЛОГИ, НЕВРОЛОГИ, ЕНДОКРИНОЛОГИ

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ОНКОЛОГИ, (ОНКО-ГЕМАТОЛОГИ, ХІМІОТЕРАПЕВТИ, МАМОЛОГИ, ОНКО-ХІРУРГИ)

ЕНДОКРИНОЛОГИ, СІМЕЙНІ ЛІКАРІ, ПЕДІАТРИ, КАРДІОЛОГИ ТА ІНШІ СПЕЦІАЛІСТИ

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АНЕСТЕЗІОЛОГИ, ХІРУРГИ

"Emergency medicine" №2(97), 2019

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X-linked myotubular myopathy and dilated cardiomyopathy as the cause of respiratory failure in a ventilated child in the ICU (case report)

Authors: V.V. Orel(1), I.V. Kyselova(1), T.L. Winder(2)
(1) — Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine
(2) — INVITAE Laboratory, San Francisco, CA, USA

Categories: Medicine of emergency

Sections: Medical forums

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Background. Centronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle disorders [1]. Myotubular myopathy, an X-linked form of CNM is characterized by neonatal hypotonia and inability to maintain unassisted respiration. The MTM1 gene, responsible for this disease, encodes myotubularin — a lipidic phosphatase involved in vesicle trafficking regulation and maturation [2]. Case report and discussion. We report a 7-month old male infant who has required mechanical ventilation since birth due to suspected neuromyopathy. Congenital adrenal hyperplasia, Pompe disease (type II glycogenosis), Prader — Willi syndrome, and SMA were excluded. Further genetic testing revealed a hemizygous variant (c. 64–2A > G) in MTM1. This variant is predicted to abolish the intron 2 splice donor site of MTM1 and has been reported in a male infant with severe X-linked myotubular myopathy [3]. Our patient’s mother and maternal grandmother were found to be heterozygous carriers of the c. 64–2A > G variant. Two variants of uncertain significance were detected in this patient’s MYH7 gene. MYH7 encodes the cardiac-specific beta heavy chain myosin protein and is a cause of autosomal dominant dilated cardiomyopathy and distal myopathy. One variant (p.Leu881Met) was inherited from the father and the other (p.Arg1749Gly) was inherited from the mother. The paternally inheri-ted variant is found in a region of the MYH7 protein where a significant number of previously reported MYH7 missense mutations are found [4]. Both MYH7 variants are absent from the ExAC public database. Thus, the genetic testing allowed us to diagnose the combined genetic pathology: myotubular myopathy and possibly dilated cardiomyopathy. This pathology causes the respiratory failure and the need of permanent respiratory support in a patient. Conclusions. The case report demonstrates importance of: 1) genetic screening in a population, especially in genetics-compromised parents, for family planning and timely detection of hereditary diseases during pregnancy; 2) early genetic testing to confirm the diagnosis of a sick child; 3) development of palliative and hospice medicine with the possibility of providing ventilation support at home by parents (guardians).


Bibliography

1. Fattori F, Maggi L, Bruno C, Cassandrini D, Codemo V, Catteruccia M, et al. Centronuclear myopathies: genotype-phenotype correlation and frequency of defined genetic forms in an Ita-lian cohort. J Neurol. 2015 Jul;262(7):1728-40.
2. Oliveira J, Oliveira ME, Kress W, Taipa R, Pires MM, Hilbert P, et al. Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database. Eur J Hum Genet. 2013 May;21(5):540-9.
3. Herman GE, Kopacz K, Zhao W, Mills PL, Metzenberg A, Das S. Characterization of mutations in fifty North American patients with X-linked myotubular myopathy. Hum Mutat. 2002 Feb;19(2):114-21.
4. Jordan DM, Kiezun A, Baxter SM, Agarwala V, Gre-en RC, Murray MF, et al. Development and validation of a computational method for assessment of missense variants in hypertrophic cardiomyopathy. Am J Hum Genet. 2011 Feb 11;88(2):183-92.

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