Left ventricular noncompaction in Duchenne muscular dystrophy

Statile, Christopher; Taylor, Michael D.; Mazur, Wojciech; Cripe, Linda H.; King, Eileen; Pratt, Jesse; Benson, D. Woodrow; Hor, Kan N.

doi:10.1186/1532-429x-15-67

Cited by 37 publications

(26 citation statements)

References 31 publications

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“…We also recognize that the LVNC phenotype may be secondary to causes other than genetic triggers, for example unfavorable LV remodeling. 7,45 With this in mind, we recognize that our study does not have longitudinal data and that we cannot document presence or absence of LV trabeculations early in life in our cohort. Although numerous potentially contributory mutations were identified using strict criteria (population conservation, evolutionary conservation and known deleteriousness of the variant, gene function), these variants may still not be disease causing.…”

Section: Discussionmentioning

confidence: 95%

Novel Genetic Triggers and Genotype–Phenotype Correlations in Patients With Left Ventricular Noncompaction

Miszalski−Jamka¹,

Jefferies

Mazur³

et al. 2017

Circ Cardiovasc Genet

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Background Left ventricular non-compaction (LVNC) is a genetically and phenotypically heterogeneous disease and, although increasingly recognized in clinical practice, there is a lack of widely accepted diagnostic criteria. We sought to identify novel genetic causes of LVNC and describe genotype-phenotype correlations. Methods and Results 190 patients from 174 families with left ventricular hypertrabeculation (LVHT) or LVNC were referred for cardiac magnetic resonance and whole exome sequencing. 425 control individuals were included to identify variants of interest (VOIs). We found an excess of 138 VOIs in 102 (59%) unrelated patients in 54 previously identified LVNC or other known cardiomyopathy genes. VOIs were found in 68 of 90 probands with LVNC and 34 of 84 probands with LVHT (76% and 40%, respectively; p<0.001). We identified 0, 1, and ≥2 VOIs in 72, 74, and 28 probands, respectively. We found increasing number of VOIs in a patient strongly correlated with several markers of disease severity, including ratio of non-compacted to compacted myocardium (p<0.001) and left ventricular ejection fraction (p=0.01). The presence of sarcomeric gene mutations was associated with increased occurrence of late gadolinium enhancement (p=0.004). Conclusions LVHT and LVNC likely represent a continuum of genotypic disease with differences in severity and variable phenotype explained, in part, by the number of VOIs and whether mutations are present in sarcomeric or non-sarcomeric genes. Presence of VOIs is common in patients with LVHT. Our findings expand the current clinical and genetic diagnostic approaches for patients with LVHT and LVNC.

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Section: Discussionmentioning

confidence: 95%

Novel Genetic Triggers and Genotype–Phenotype Correlations in Patients With Left Ventricular Noncompaction

Miszalski−Jamka¹,

Jefferies

Mazur³

et al. 2017

Circ Cardiovasc Genet

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100

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“…Finally, diagnosing the underlying condition enables more accurate genetic counseling for the family. Table 2 Syndromes and copy number variants (CNV) associated with LVNC Syndromes associated with aneuploidies Turner syndrome [1,43] Trisomy 21 [27] Trisomy 18 [5] Trisomy 13 [25] Syndromes associated with copy number variations Velocardiofacial syndrome [21,29] 1p36 deletion syndrome [4] Syndromes associated with neuromuscular diseases Duchenne muscular dystrophy; Becker muscular dystrophy [17,38] Limb girdle muscular dystrophy [20] Multiminicore disease [37] Other syndromes Sotos syndrome [24] Marfan syndrome [18] Noonan syndrome [2] LEOPARD syndrome [19] Cornelia De Lange syndrome [9] Roifman syndrome [22] Hypomelanosis of Ito [8] Nail patella syndrome [12] Other CNV 8p23.1 deletion [6] Trisomic for the 4q31 ? qter region and monosomic for the 1q43 ?…”

Section: Discussionmentioning

confidence: 99%

Left Ventricular Non-compaction: Is It Genetic?

et al. 2015

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Left ventricular non-compaction (LVNC) is reported to affect 0.14 % of the pediatric population. The etiology is heterogeneous and includes a wide number of genetic causes. As an illustration, we report two patients with LVNC who were diagnosed with a genetic syndrome. We then review the literature and suggest a diagnostic algorithm to evaluate individuals with LVNC. Case 1 is a 15-month-old girl who presented with hypotonia, global developmental delay, congenital heart defect (including LVNC) and facial dysmorphism. Case 2 is a 7-month-old girl with hypotonia, seizures, laryngomalacia and LVNC. We performed chromosomal microarray for both our patients and detected chromosome 1p36 microdeletion. We reviewed the literature for other genetic causes of LVNC and formulated a diagnostic algorithm, which includes assessment for syndromic disorders, inborn error of metabolism, copy number variants and non-syndromic monogenic disorder associated with LVNC. LVNC is a relatively newly recognized entity, with heterogeneity in underlying etiology. For a systematic approach of evaluating the underlying cause to improve clinical care of these patients, a diagnostic algorithm for genetic evaluation of patients with LVNC is proposed.

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“…Various specific NMDs such as Becker muscular dystrophy, Barth syndrome, mitochondriopathy, dystrobrevinopathy, myotonic dystrophy type 1 and type 2, zaspopathy, laminopathy, myoadenylatedeaminase deficiency, Duchenne muscular dystrophy, Charcot-Marie-Tooth disease 1A, inclusion-body myopathy, and oculopharyngodistal myopathy have been described in association with LVHT [11,[18][19][20]. It is unknown if this association is coincidental or causal.…”

Section: Discussionmentioning

confidence: 99%