X-Linked Myotubular Myopathy and Chylothorax

ARTICLE IN PRESS

Neuromuscular Disorders xxx (2007) xxx–xxx www.elsevier.com/locate/nmd Case report X-linked myotubular myopathy and chylothorax

Koenraad Smets *

Department of Neonatology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium

Received 10 August 2007; received in revised form 4 October 2007; accepted 24 October 2007

Abstract

X-linked myotubular myopathy usually presents at birth with hypotonia and respiratory distress. Phenotypic presentation, however, can be extreme variable. We report on a newborn baby, who presented with the severe form of the disease. In the second week of life, he developed a clinically relevant chylothorax, needing drainage and treatment with octreotide acetate. Pleural eﬀusions are frequently described in patients with congenital myotonic dystrophy. To our knowledge, the association of chylothorax and X-linked myotubular myopathy has not been described to date. As chylothorax could not be attributed to any evident condition in this child, perhaps it may be added to the clinical spectrum of X-linked myotubular myopathy. Ó 2007 Elsevier B.V. All rights reserved.

Keywords: X-linked myotubular myopathy; Chylothorax

1. Introduction drainage (Fig. 1). Laboratory examination was compatible with chylothorax (5230 white blood cells/ll, 98% lympho- Congenital myopathies often present with hypotonia cytes; chylomicrons were present; triglycerides 746 mg/dl). and respiratory distress from birth, although their expres- There were no central venous catheters in place who could sion may be delayed. In most cases muscle biopsy is war- have caused thrombosis, impairing lymphatic flow, neither ranted for definitive diagnosis. In some instances could any other risk factor for chylothorax be identified. associated systemic features point at the final diagnosis. Because interruption of enteral feeding failed to control In congenital myotonic dystrophy, e.g., the mother will the chylothorax with daily losses approximating 400 ml, show mild facial weakness and clinical myotonia. Like- treatment with octreotide acetate, a long-acting synthetic wise, hydrops and/or pleural effusions in a newborn with analog of somatostatin, was instituted [1]. Chylothorax severe hypotonia is suggestive of congenital myotonic gradually resolved and enteral feeding with medium-chain dystrophy. triglyceride enriched formula was introduced without prob- lems. Muscle biopsy disclosed typical features of X-linked myotubular myopathy (Fig. 2). The MTM1 gene was 2. Case report sequenced and revealed a C.1261-10 A>G mutation, confirming the diagnosis [2]. The baby died at home with A male newborn baby of two non-consanguineous palliative care at the age of 4 months. Autopsy was not Turkish parents presented from birth with generalized performed. hypotonia and respiratory distress, requiring artificial ven- tilation. On day 11, 5 days after introduction of gavage feeding, he developed bilateral pleural effusions, requiring 3. Discussion

* Tel.: +32 9 2403535; fax: +32 9 2406105. To our knowledge, this is the ﬁrst report on a E-mail address: [email protected] neonate with X-linked myotubular myopathy who

Please cite this article in press as: Smets K, X-linked myotubular myopathy and chylothorax, Neuromuscul Disord (2007), doi:10.1016/j.nmd.2007.10.004 ARTICLE IN PRESS

2 K. Smets / Neuromuscular Disorders xxx (2007) xxx–xxx

developed a clinically relevant chylothorax. When not a postoperative complication, chylothorax probably results from a malformation of the thoracic duct, although in many cases no apparent abnormality can be found. Searching the literature for association between chylothorax and congenital myopathies, we found a case report that was very similar to ours. Chylothorax was described in a boy of healthy Turkish parents, who presented with lack of spontaneous movements at birth and who died at the age of 9 weeks [3]. Muscle biopsy con- firmed congenital actin myopathy together with nemaline bodies and intranuclear rods. In that baby a mutation of the ACTA1 gene in exon 4 was found. For the rest pleural effusions with or without hydrops are frequently described in cases of congenital myotonic dystrophy Fig. 1. Chest X-ray showing bilateral pleural effusions (arrows). [4,5]. However, expansion of CTG repeats was excluded in our patient. An X-linked recessive transmission of chylothorax has been suggested [6]. As no other evident condition linked to chylothorax could be found, perhaps chylothorax may be classified under one of the systemic features of X-linked myotubular myopathy, as it is the case for pleural effusions and congenital myotonic dystrophy.

Acknowledgement

The author thanks Em. Prof. dr. Jean-Jacques Martin, Institute Born-Bunge, University of Antwerp, Wilrijk, Bel- gium, for processing and evaluation of the muscle biopsy.

References

[1] Stajich GV, Ashworth L. Octreotide. Neonatal Netw 2006;25: 365–9. [2] de Gouyon BM, Zhao W, Laporte J, Mandel J-L, Metzenberg A, Herman GE. Characterization of mutations in the myotubularin gene in twenty six patients with X-linked myotubular myopathy. Hum Mol Genet 1997;6:1499–504. [3] Schro¨der JM, Durling H, Laing N. Actin myopathy with nemaline bodies, intranuclear rods, and a heterozygous mutation in ACTA1 (Asp154Asn). Acta Neuropathol 2004;108:250–6. [4] Curry CJ, Chopra D, Finer NN. Hydrops and pleural effusions in congenital myotonic dystrophy. J Pediatr 1988;113:555–7. [5] Stratton RF, Patterson RM. DNA confirmation of congenital myotonic dystrophy in non-immune hydrops fetalis. Prenat Diagn Fig. 2. (a) Muscle biopsy, transverse section. On this hematoxylin–eosin 1993;13:1027–30. stained preparation, all the small muscle fibres contain a central nucleus [6] Reece EA, Lockwood CJ, Rizzo N, Pilu G, Bovicelli L, Hobbins corresponding to the description of a myotube. (b) NADH-TR staining. JC. Intrinsic intrathoracic malformations of the fetus: sonograph- The NADH-TR activity is mainly centrally located in the muscle fibres. ic detection and clinical presentation. Obstet Gynecol There is a faint radial distribution to be seen in the lighter outer rim. 1987;70:627–32.

Please cite this article in press as: Smets K, X-linked myotubular myopathy and chylothorax, Neuromuscul Disord (2007), doi:10.1016/j.nmd.2007.10.004