Dataset Information

Isolated vocal cord paralysis in two siblings with compound heterozygous variants in MUSK: Expanding the phenotypic spectrum.

ABSTRACT: The congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by perturbations in signal transduction at the neuromuscular junction. Defects in muscle, skeletal, receptor tyrosine kinase (MuSK) cause two distinct phenotypes: fetal akinesia with multiple congenital anomalies (Fetal akinesia deformation sequence [MIM:208150]) and early onset congenital myasthenia (myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency [MIM:616325]). Myasthenia due to MuSK deficiency has variable clinical features, ranging from a milder presentation of isolated late-onset proximal muscle weakness; to a severe presentation of prenatal-onset diffuse weakness, ophthalmoplegia, respiratory failure, and vocal cord paralysis (VCP). Here, we propose to expand the phenotypic spectrum for MuSK deficiency to include isolated VCP with the absence of other classical myasthenic symptoms. We evaluated two brothers who presented in the neonatal period with respiratory failure secondary to isolated VCP. Research-based exome sequencing revealed biallelic likely pathogenic variants in MUSK (MIM:601296). Both children had normal gross motor and fine motor development. One brother had speech delay, likely due to a combination of tracheostomy status and ankyloglossia. This case report suggests that CMS should be on the differential diagnosis for familial recurrence of VCP.

SUBMITTER: Murali C

PROVIDER: S-EPMC6924566 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Isolated vocal cord paralysis in two siblings with compound heterozygous variants in MUSK: Expanding the phenotypic spectrum.

Murali Chaya C Li Dong D Grand Katheryn K Hakonarson Hakon H Bhoj Elizabeth E

American journal of medical genetics. Part A 20190204 4

The congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by perturbations in signal transduction at the neuromuscular junction. Defects in muscle, skeletal, receptor tyrosine kinase (MuSK) cause two distinct phenotypes: fetal akinesia with multiple congenital anomalies (Fetal akinesia deformation sequence [MIM:208150]) and early onset congenital myasthenia (myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency [MIM:616325]). Myasthen ...[more]

PMID: 30719842

Similar Datasets

Project description:ImportanceUnilateral vocal fold paralysis (UVFP) is a common and life-changing complication of cancer, trauma, and an estimated 500 000 head, neck, and chest surgeries performed annually in the US, among other causes (eg, idiopathic). Consequent disabilities are profound and often permanent and can include severe voice, swallowing, and breathing dysfunction and concomitant anxiety, isolation, and fear. Physiological measures often correlate poorly with patient-reported disability. The measure described herein was designed to be a comprehensive, psychometrically sound UVFP-specific patient-reported outcome measure (PROM) for use in clinical trials or at point of care.ObjectiveTo evaluate the reliability and validity of the CoPE (vocal Cord Paralysis Experience) PROM in a nationally representative sample for both clinical and research use.Design, setting, and participantsThis survey validation study was performed at 34 tertiary care centers across the US and included English-speaking adults with unilateral vocal fold immobility confirmed via laryngoscopy.Main outcomes and measuresReliability (internal consistency, alternate form, and test-retest) and validity (convergent and known-group).ResultsIn total, 613 patients (mean [SD] age, 58 [15.3] years; 394 [64.5%] women) were recruited, and 555 (92.3%) completed surveys for all time points. Internal consistency was high in the overall 22-item PROM and psychosocial, swallow, and voice subscales (Cronbach α > 0.91). Intraclass correlations for individuals between the baseline and 2-week administrations were moderate for the overall score and subscales (intraclass correlations range, 0.66-0.80). There were significant differences between the online and 2-week paper administrations for the overall score and voice and psychosocial subscales (overall scale mean: 54.4 [95% CI, 49.7-59.1] vs 48.9 [95% CI, 43.7-54.0] at 2 weeks). The confirmatory model was found to be suitably fitted based on average r2 values 0.5 or greater for subscale and overall scores. Correlations between subscales and existing PROMs (Voice-Related Quality of Life, Eating Assessment Tool, and Communication Participation Item Bank) were all greater than 0.69, and mean PROM subscale scores were significantly different across known quartiles of existing PROMs.Conclusions and relevanceThe findings of this survey validation study suggest that the CoPE PROM could serve as a psychometrically sound, comprehensive measure of UVFP-attributed disability suitable for use in clinical and research settings to assess within-person changes. The results will inform a user manual to facilitate use in clinical trials comparing the effectiveness and durability of treatments including behavioral (speech therapy), temporary (eg, injection augmentation), and permanent surgical treatments for UVFP.

Dataset Information

Isolated vocal cord paralysis in two siblings with compound heterozygous variants in MUSK: Expanding the phenotypic spectrum.

Publications

Isolated vocal cord paralysis in two siblings with compound heterozygous variants in MUSK: Expanding the phenotypic spectrum.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets