Cardiac care of children with dystrophinopathy and females carrying DMD-gene variations

Bourke, John; Turner, Cathy; Bradlow, William; Chikermane, Ashish; Coats, Caroline; Fenton, Matthew J.; Ilina, Maria; Johnson, Alexandra; Kapetanakis, Stam; Kuhwald, Lisa; Morley-Davies, Adrian; Quinlivan, Ros; Savvatis, Konstantinos; Schiava, Marianela; Yousef, Zaheer; Guglieri, Michela

doi:10.1136/openhrt-2022-001977

Cited by 11 publications

(7 citation statements)

References 73 publications

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“…Three of the genes ( ABCB11 , COL4A3 , and COL4A4 ) have been reported in association with both autosomal recessive and autosomal dominant inheritance (Table 2). 14–60…”

Section: Resultsmentioning

confidence: 99%

“…Pregnancy manifestations reported in the literature for carriers of these genes include cholestasis of pregnancy ( ABCB11 ); gestational hypertensive disorders ( COL4A3 , COL4A4 , COL4A5 , and GLA ); maternal cardiomyopathy ( DMD ); acute fatty liver of pregnancy or hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome ( CPT1A , and HADHA ); maternal virilization ( CYP19A1 ), hyperammonemic crisis ( OTC ); and maternal hemorrhage ( F9 and F11 ) (Tables 1 and 2). 14–60 Tables 1 and 2 summarize the genes, their potential manifestations in pregnancy, and published guidance for follow-up testing or management in pregnancy that could be considered. The reported incidence of pregnancy complications in carriers ranged from 10% to 62% depending on the gene involved, but information was limited for most of the conditions.…”

Section: Resultsmentioning

confidence: 99%

“…The reported incidence of pregnancy complications in carriers ranged from 10% to 62% depending on the gene involved, but information was limited for most of the conditions. 14–60 Recommendations for management of carriers were identified for 11 of the 12 genes (Tables 1 and 2).…”

Section: Resultsmentioning

confidence: 99%

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Reproductive Carrier Screening Results With Maternal Health Implications During Pregnancy

Souter

Prigmore

Becraft

et al. 2023

Obstetrics &Amp; Gynecology

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OBJECTIVE: To identify conditions on a reproductive carrier screening panel with the potential for carrier manifestations during pregnancy and review the implications for obstetric care. METHODS: This was a retrospective cross-sectional study of consecutive samples from female patients aged 18–55 years submitted to a commercial laboratory for a 274-gene carrier screening panel (January 2020 to September 2022). A literature review was performed to identify genes on the panel with potential for pregnancy complications in carriers. Carrier expression and published recommendations for clinical management were reviewed. RESULTS: We identified 12 genes with potential for carrier manifestations during pregnancy based on reports in the literature: nine with manifestations irrespective of the fetal genetic status (ABCB11, COL4A3, COL4A4, COL4A5, DMD, F9, F11, GLA, and OTC) and three (CPT1A, CYP19A1, and HADHA) with manifestations only if the fetus is affected by the condition. Manifestations included cardiomyopathy, hemorrhage, gestational hypertensive disorders, cholestasis of pregnancy, acute fatty liver, hyperammonemic crisis, and maternal virilization. Published recommendations for carrier management were identified for 11 of the 12 genes. Of 91,637 tests performed during the study period, a pathogenic or likely pathogenic variant was identified in 2,139 (2.3%), giving a carrier frequency for any of the 12 genes of 1 in 43 (95% CI 1/41–45) 1,826 (2.0%) of the study population were identified as carriers for one of the nine genes with the potential for carrier manifestations irrespective of an affected or unaffected fetus. CONCLUSION: Approximately 1 in 40 female patients were identified as carriers for a condition with potential for maternal manifestations in pregnancy, including some serious or even life-threatening complications. Obstetric care professionals should be aware of the possibility of pregnancy complications among carriers and the available recommendations for management. FUNDING SOURCE: This study was funded by Natera, Inc.

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“…Three of the genes ( ABCB11 , COL4A3 , and COL4A4 ) have been reported in association with both autosomal recessive and autosomal dominant inheritance (Table 2). 14–60…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Reproductive Carrier Screening Results With Maternal Health Implications During Pregnancy

Souter

Prigmore

Becraft

et al. 2023

Obstetrics &Amp; Gynecology

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“…Cough augmentation devices are recommended for PCF <270 L/min, affecting over 70% of our cohort since age 16 [21]. Individuals with DMD should receive annual cardiac follow‐up starting at age 10 [35]. Cardiomyopathy with reduced LVEF (<50%) was identified in 40.3% by the age of 16 years.…”

Section: Discussionmentioning

confidence: 99%

Functional abilities, respiratory and cardiac function in a large cohort of adults with Duchenne muscular dystrophy treated with glucocorticoids

Schiava,

Lofra,

Bourke

et al. 2024

Euro J of Neurology

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Background and purposeThe transition to adult services, and subsequent glucocorticoid management, is critical in adults with Duchenne muscular dystrophy. This study aims (1) to describe treatment, functional abilities, respiratory and cardiac status during transition to adulthood and adult stages; and (2) to explore the association between glucocorticoid treatment after loss of ambulation (LOA) and late‐stage clinical outcomes.MethodsThis was a retrospective single‐centre study on individuals with Duchenne muscular dystrophy (≥16 years old) between 1986 and 2022. Logistic regression, Cox proportional hazards models and survival analyses were conducted utilizing data from clinical records.ResultsIn all, 112 individuals were included. Mean age was 23.4 ± 5.2 years and mean follow‐up was 18.5 ± 5.5 years. At last assessment, 47.2% were on glucocorticoids; the mean dose of prednisone was 0.38 ± 0.13 mg/kg/day and of deflazacort 0.43 ± 0.16 mg/kg/day. At age 16 years, motor function limitations included using a manual wheelchair (89.7%), standing (87.9%), transferring from a wheelchair (86.2%) and turning in bed (53.4%); 77.5% had a peak cough flow <270 L/min, 53.3% a forced vital capacity percentage of predicted <50% and 40.3% a left ventricular ejection fraction <50%. Glucocorticoids after LOA reduced the risk and delayed the time to difficulties balancing in the wheelchair, loss of hand to mouth function, forced vital capacity percentage of predicted <30% and forced vital capacity <1 L and were associated with lower frequency of left ventricular ejection fraction <50%, without differences between prednisone and deflazacort. Glucocorticoid dose did not differ by functional, respiratory or cardiac status.ConclusionGlucocorticoids after LOA preserve late‐stage functional abilities, respiratory and cardiac function. It is suggested using functional abilities, respiratory and cardiac status at transition stages for adult services planning.

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“…Up to 20% of them have mild-to-moderate muscle weakness, CK levels are elevated in about 50–60% of the cases, and dilated cardiomyopathy may also be present in about 8% [ 10 ]. Even in the absence of skeletal muscle symptoms, females with DMD gene variations are estimated to have a lifetime risk of developing cardiomyopathy of up to 17% [ 11 ]. Further symptoms that can present include clumsiness in childhood, myalgia/cramps, unexplained abdominal or chest pain, pseudohypertrophy of the calf muscle, and severe gait problems [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

An Ultra-Rare Manifestation of an X-Linked Recessive Disorder: Duchenne Muscular Dystrophy in a Female Patient

Szücs

Pinti

Haltrich

et al. 2022

IJMS

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Duchenne muscular dystrophy (DMD) is the most common inherited muscle dystrophy. Patients are characterized by muscle weakness, gross motor delay, and elevated serum creatinine kinase (CK) levels. The disease is caused by mutations in the DMD gene located on the X chromosome. Due to the X-linked recessive inheritance pattern, DMD most commonly affects males, who are generally diagnosed between the age of 3–5 years. Here we present an ultra-rare manifestation of DMD in a female patient. Cytogenetic examination showed that she has a t(X;10)(p21.1;p12.1) translocation, which turned out to affect the DMD gene with one of the breakpoints located in exon 54 (detected by genome sequencing). The X-inactivation test revealed skewed X-inactivation (ratio 99:1). Muscle histology and dystrophin immunohistochemistry showed severe dystrophic changes and highly reduced dystrophin expression, respectively. These results, in accordance with the clinical picture and a highly elevated serum CK, led to the diagnosis of DMD. In conclusion, although in very rare cases, DMD can manifest in female patients as well. In this case, a balanced X-autosome reciprocal translocation disrupts the DMD gene and skewed X-inactivation leads to the manifestation of the DMD phenotype.

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Cardiac care of children with dystrophinopathy and females carrying DMD-gene variations

Cited by 11 publications

References 73 publications

Reproductive Carrier Screening Results With Maternal Health Implications During Pregnancy

Reproductive Carrier Screening Results With Maternal Health Implications During Pregnancy

Functional abilities, respiratory and cardiac function in a large cohort of adults with Duchenne muscular dystrophy treated with glucocorticoids

An Ultra-Rare Manifestation of an X-Linked Recessive Disorder: Duchenne Muscular Dystrophy in a Female Patient

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