Hypertrophic cardiomyopathy in Donohue syndrome

Termote, J.; Breur, Johannes M.P.J.; Vroede, Monique A. M. J. de

doi:10.1017/s1047951115002437

Cited by 10 publications

(9 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ASD has been reported in extreme insulin resistance (Rabson‐Medenthal phenotype) . Two cases of obstructive hypertrophic cardiomyopathy have been recently reported in patients with Donohue syndrome . A literature survey has revealed that hypertrophic cardiomyopathy was present in 30% of patients with the syndrome and can be fatal …”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal dysmotility and pancreatic insufficiency in 2 siblings with Donohue syndrome

et al. 2016

View full text Add to dashboard Cite

Donohue syndrome is a rare congenital syndrome of insulin-resistance and abnormal glucose homeostasis, caused by mutations in the insulin receptor (INSR) gene. It is characterized by specific phenotypic and clinical features and the diagnosis is based on clinical, biochemical and genetic criteria. We report 2 siblings with Donohue syndrome (cases 1, 2) with multiple clinical and biochemical characteristics. Both patients shared the same mutation and presented with intra-uterine growth restriction, failure to thrive, fasting hyperinsulinaemic hypoglycaemia and episodic post-prandial hyperglycaemia. Less common clinical features were also present, such as atrial septal defect and biventricular hypertrophy, clotting disorders, abnormal liver function tests and nephrocalcinosis. Interestingly, 2 previously unrecognized manifestations of the syndrome were also identified: severe gastrointestinal dysmotility (case 1) and exocrine pancreatic insufficiency (case 2). The co-existence of all the above clinical features makes these cases extremely rare. Gastrointestinal dysmotility should always be considered as a potentially fatal feature in patients with the syndrome, due to the complexity of the possible co-morbidities. In addition, our clinical experience for the first time suggests that pancreatic exocrine insufficiency may offer a possible explanation for the growth retardation observed in some patients with this syndrome. Our finding that replacement treatment with pancreatic enzymes improved weight gain (case 2) implies that all patients with Donohue syndrome should be investigated for exocrine pancreatic insufficiency.

show abstract

Section: Discussionmentioning

confidence: 99%

Gastrointestinal dysmotility and pancreatic insufficiency in 2 siblings with Donohue syndrome

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In parallel, the IGF-I receptor compensates at least partially for the defective IR function [Lamothe et al, 1998;McDonald et al, 2007]; the hyperinsulinism resulting from the absence of IR, acting through the IGF-I receptor, can therefore cause pseudoacromegalic growth in soft tissues, particularly in the heart and result in HCM [Ren et al, 1999;Deosch and Muslin, 2008]. The latter is present in 30% of DS infants and leads to death in 85% of these patients [Termote et al, 2016;Ben Harouch et al, 2019]; prenatal diagnosis is therefore essential to allow early neonatal management. Another characteristic of DS seen in prenatal ultrasound is virilization in girls because pseudoacromegalic growth affects in particular sex hormone-dependent tissues (insulin increases the effects of gonadotropins synergistically) and hyperinsulinism also promotes hyperandrogenism [Nestler, 1997;Semple et al, 2011].…”

Section: Discussionmentioning

confidence: 99%

Intrauterine Growth Restriction and Hypertrophic Cardiomyopathy as Prenatal Ultrasound Findings in a Case of Leprechaunism

et al. 2020

View full text Add to dashboard Cite

Donohue syndrome (leprechaunism; OMIM *246200) is a rare and often lethal autosomal recessive disease caused by mutations in the <i>INSR</i> gene. We report the case of a 29-year-old pregnant woman, primigravida, who was referred at 33 weeks of gestation for severe intrauterine growth restriction (IUGR). Ultrasound examination found severe IUGR associated with an obstructive hypertrophic cardiomyopathy (HCM), confirmed postnatally. The newborn’s blood glucose level fluctuated from fasting hypoglycemia to postprandial hyperglycemia. The infant was found to be homozygous for a novel missense pathogenic variant, c.632C>T (p.T211l), in exon 2 of the <i>INSR</i> gene, predicted to result in an abnormal insulin receptor. To our knowledge, this is the first report of leprechaunism being revealed by IUGR and HCM during the prenatal period. Clinicians should keep in mind that the association of these prenatal signs could indicate leprechaunism and specific early neonatal management could be proposed, in particular with recombinant human insulin-like growth factor-I.

show abstract

“…Features of the disease are severe intra-uterine growth retardation, diminished fat and muscle tissue, characteristic facies, and precocious puberty [38]. Termote et al reviewed the literature of leprechaunism between 1980 and 2014 and retrieved 81 cases of leprechaunism of which 39 patients underwent cardiac examination [39]. Sixtyone percent of these patients showed signs of CH (Table 3).…”

Section: Insulin Resistance Syndromesmentioning

confidence: 99%

“…Sixtyone percent of these patients showed signs of CH (Table 3). Mortality is extremely high in patients with leprechaunism [42][43][44] and 85% of the patients with CH die from heart failure [39]. The reported pattern of hypertrophy is mainly septal causing obstruction of the aortic outflow tract.…”

Section: Insulin Resistance Syndromesmentioning

confidence: 99%

“…Insulin binding to human leprechaunism fibroblasts is impaired, but mitogenic response is noted at high supraphysiologic concentrations of insulin and this response can be blocked by an antibody to the IGF-I receptor [100]. In leprechaunism, which is the most severe form of insulin resistance characterized by very high levels of insulin (up to 6000 μU/ml), the CH is very severe and often the cause of death [39]. This is most pronounced in patients with a null mutation of the insulin receptor [101].…”

Section: Igf-1mentioning

confidence: 99%

See 1 more Smart Citation

Neonatal cardiac hypertrophy: the role of hyperinsulinism—a review of literature

et al. 2019

Self Cite

View full text Add to dashboard Cite

Hypertrophic cardiomyopathy (HCM) in neonates is a rare and heterogeneous disorder which is characterized by hypertrophy of heart with histological and functional disruption of the myocardial structure/composition. The prognosis of HCM depends on the underlying diagnosis. In this review, we emphasize the importance to consider hyperinsulinism in the differential diagnosis of HCM, as hyperinsulinism is widely associated with cardiac hypertrophy (CH) which cannot be distinguished from HCM on echocardiographic examination. We supply an overview of the incidence and treatment strategies of neonatal CH in a broad spectrum of hyperinsulinemic diseases. Reviewing the literature, we found that CH is reported in 13 to 44% of infants of diabetic mothers, in approximately 40% of infants with congenital hyperinsulinism, in 61% of infants with leprechaunism and in 48 to 61% of the patients with congenital generalized lipodystrophy. The correct diagnosis is of importance since there is a large variation in prognoses and there are various strategies to treat CH in hyperinsulinemic diseases. Conclusion: The relationship between CH and hyperinsulism has implications for clinical practice as it might help to establish the correct diagnosis in neonates with cardiac hypertrophy which has both prognostic and therapeutic consequences. In addition, CH should be recognized as a potential comorbidity which might necessitate treatment in all neonates with known hyperinsulinism. What is Known: • Hyperinsulinism is currently not acknowledged as a cause of hypertrophic cardiomyopathy (HCM) in textbooks and recent Pediatric Cardiomyopathy Registry publications. What is New: • This article presents an overview of the literature of hyperinsulinism in neonates and infants showing that hyperinsulinism is associated with cardiac hypertrophy (CH) in a broad range of hyperinsulinemic diseases. • As CH cannot be distinguished from HCM on echocardiographic examination, we emphasize the importance to consider hyperinsulinism in the differential diagnosis of HCM/CH as establishing the correct diagnosis has both prognostic and therapeutic consequences.

show abstract

Hypertrophic cardiomyopathy in Donohue syndrome

Cited by 10 publications

References 9 publications

Gastrointestinal dysmotility and pancreatic insufficiency in 2 siblings with Donohue syndrome

Gastrointestinal dysmotility and pancreatic insufficiency in 2 siblings with Donohue syndrome

Intrauterine Growth Restriction and Hypertrophic Cardiomyopathy as Prenatal Ultrasound Findings in a Case of Leprechaunism

Neonatal cardiac hypertrophy: the role of hyperinsulinism—a review of literature

Contact Info

Product

Resources

About