Infantile-Onset LMNA-Related Congenital Muscular Dystrophy Presenting as Torticollis: A Case Report

Article information

J Electrodiagn Neuromuscul Dis. 2023;25(1):34-37

Publication date (electronic) : 2023 April 24

doi : https://doi.org/10.18214/jend.2022.00178

Ji Ae Kim, Dong Hyun Ye, Hee Tae Shin, Seung Hak Lee, Eun Jae Ko

Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Corresponding author: Eun Jae Ko Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Tel: +82-2-3010-3912 Fax: +82-2-3010-6964 E-mail: ejko.amc@gmail.com

Received 2022 August 29; Revised 2022 November 24; Accepted 2022 November 25.

Abstract

Introduction

Congenital muscular dystrophies are genetic myopathies with hypotonia, muscle weakness, and delayed development from infancy [1]. Lamins are intermediate filament proteins, which are essential for nuclear structure. Laminopathies caused by lamin A (LMNA) mutations can be grouped into diseases affecting the striated muscle, peripheral nerve, and adipose tissue. In particular, laminopathies involving striated muscle can cause various types of muscular dystrophy, such as Emery-Dreifuss muscular dystrophy (EDMD), congenital muscular dystrophy, and limb girdle muscular dystrophy type 1B [2].

Congenital muscular dystrophy with LMNA mutations associated with congenital onset has been found to be more severe than EDMD with school-age onset [3]. In this case report, we present the clinical and electromyographic features of a patient with congenital muscular dystrophy who initially presented with torticollis.

Case Report

A 7-month-old infant was referred to the pediatric rehabilitation department outpatient clinic with a chief complaint of torticollis. She was the first child of consanguineous parents and was born at term with a birth weight of 3,410 g by cesarean section after an uncomplicated pregnancy. There were no perinatal problems, and at the time of birth, the infant’s sucking and crying were strong. No family history of neuromuscular disease was reported.

A physical examination at 7 months of age showed head tilt to the right side when the infant sat with assistance. There was no palpable neck mass, the range of head tilting was 45° on both sides, and the range of head rotation was 90° on both sides. The head righting reaction was unobtainable on both sides due to weakness of the neck muscles. Unilateral occipital flattening was observed on the right side. The deep tendon reflexes were hypoactive in both the upper and lower extremities. The Babinski sign was equivocal, and there was no ankle clonus. When performing the traction reaction test, head lagging was observed, and during the Landau reaction, the head raised to the trunk level. She could turn over from the supine to prone position, but she could not sit alone and raise her head in the prone position.

Since the patient was hypotonic and presented with gross motor delays, she was admitted to the Department of Pediatric Rehabilitation Medicine for further evaluation. Neck sonography revealed asymmetric thinning of the right sternocleidomastoid muscle without definite evidence of fibromatosis colli (Fig. 1). The serum creatine kinase (CK) level was 2,131 U/L, and brain magnetic resonance imaging revealed enlarged subarachnoid fluid spaces in the supratentorial brain with enlarged subarachnoid fluid in the frontotemporal region and prominent retrocerebellar cerebrospinal fluid. Echocardiography was normal.

Fig. 1.

Ultrasonography findings of the sternocleidomastoid muscle (SCM). (A) The left SCM thickness was measured as 0.37 cm. (B) The right SCM thickness was measured as 0.19 cm. There was asymmetric thinning of the right SCM without any fibromatosis colli.

A nerve conduction study and electromyography (EMG) were conducted for the hypotonia workup. In the nerve conduction study, left median motor, left sensory, left tibial motor, and sural sensory conduction did not reveal any abnormalities (Table 1). The EMG showed fibrillation potentials in the right gastrocnemius (medial head) and vastus medialis muscles. No abnormal spontaneous activity was observed in the right tibialis anterior muscle (Table 2). It was difficult to accurately evaluate the morphology of the motor unit action potential due to poor cooperation, but there did not seem to be any definite abnormalities, including long or short duration or large or small amplitudes. The clinical findings and electrodiagnostic tests suggested the possibility of hereditary myopathy or a motor neuron disorder. Because the serum CK level was high, muscular dystrophy was more strongly suspected than motor neuron disease or congenital myopathy in this patient.

Table 1.

Nerve Conduction Study Findings

Table 2.

Electromyography Study Findings

Based on the above results, we proceeded with genetic testing to confirm the diagnosis. The genetic tests of the SMN1 gene (for spinal muscular atrophy) and DMD gene (for progressive muscular dystrophy) were negative. However, next-generation sequencing for the muscular dystrophy panel with the Illumina MiSeq system (Illumina Inc., San Diego, CA, USA) targeting 30 genes showed a c.745C>T (p.Arg249Trp) mutation in the LMNA gene, which was classified as a pathogenic variant. Genetic testing of the patient’s mother was performed, and a very low concentration of mosaicism of the c.745C>T (p.Arg249Trp) (p.R249W) mutation of the LMNA gene was found. p.R249W is a mutation reported in patients with congenital muscular dystrophy.

At 8 months of age, intermittent aspiration signs were observed, and the patient was hospitalized for pneumonia, at which point she started nasogastric tube feeding. At 23 months of age, she was assessed with the Bayley Scales of Infant Development-II. While the mental developmental index was 100 (within normal limits), the motor index was < 50 (i.e., more than 3 standard deviations below the mean). She was not able to sit independently or stand with hand support, but was able to flip, crawl, and maintain a sitting position with support. Until 31 months of age, the patient did not need respiratory support requiring a tracheostomy or ventilator.

Written informed consent by the patients was waived due to a retrospective nature of our study.

Discussion

The case described herein is a very rare early form of laminopathy presenting as severe congenital muscular dystrophy; this diagnosis was inferred on the basis of electrodiagnostic and laboratory findings and then confirmed with genetic testing. The LMNA gene codes for lamin A, which constitutes the nucleus, and a heterozygous de novo mutation causes severe early-onset congenital muscular dystrophies. A previous report found that all children with LMNA-related congenital muscular dystrophy showed rapid weakness in cervical and axial muscle strength that rarely progressed afterward [4].

A recent study showed that about 67% of LMNA-related congenital muscular dystrophy patients acquired independent ambulation by the age of 1.2 years; however, 85% of them eventually lost the ability. In contrast, the patient in this case report did not acquire the ability to ambulate until 23 months of age. According to previous reports, the c.745C>T (p.Arg249Trp) mutation is most common (20%), and it is known to be associated with a more severe prognosis [5,6].

Congenital muscular dystrophy is known to present normal electrophysiological findings in motor and sensory nerve conduction studies. In addition, needle electromyographic studies usually show absent or sparse positive sharp waves and fibrillation. Furthermore, polyphasic motor unit action potentials with decreased duration and amplitude appear [7]. In this case, the patient was too young to adequately evaluate the characteristics of motor unit action potentials; however, rare abnormal spontaneous activity was detected. These results suggested congenital myopathy, and congenital muscular dystrophy was suspected due to the high CK level.

Previous reports suggest that LMNA-related congenital muscular dystrophy presents with early-onset, life-threatening respiratory insufficiency [4,8]. Ben Yaou et al. [5] reported that non-ambulating patients showed a disease course with more severe progression of respiratory complications early in infancy.

LMNA-related congenital muscular dystrophy is a completely different disease entity from EDMD, where the LMNA gene mutation was first identified [9]. EDMD presents as child-onset slowly progressive muscle wasting with preceding contracture [10].

It may be easy to suspect neuromuscular disease in patients with a severe progressing course of LMNA-related congenital muscular dystrophy. However, the differential diagnosis is difficult in patients in early infancy before disease progression. In particular, when the chief complaint is torticollis, as it was in this case, clinicians may not consider congenital muscular dystrophy in the differential diagnosis .

There are few reports presenting nerve conduction and EMG studies of LMNA-related congenital muscular dystrophy; therefore, this case makes a meaningful contribution to the literature. In addition, this case shows that patients with early-onset congenital muscular dystrophy could present with clinical torticollis due to axial muscle weakness. It is important for clinicians to examine infants with torticollis thoroughly, since it may be the first sign of neuromuscular diseases.

Article information Continued