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

Abstract

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.

Pancreas agenesis and fetal growth: a semiquantitative analysis

“…Thus, growth restriction found in neonates with PA is most likely attributable to the absence of insulin. In infants with Donohue syndrome, a rare genetic disorder characterized by absence of insulin receptors, fetuses are also undergrown ( 48 ). The essential role of the pancreas for fetal growth is also shown by experimental pancreatectomy in sheep ( 49 ).…”

Hypertrophic Cardiomyopathy in Infants from the Perspective of Cardiomyocyte Maturation

“… 71) Hyperinsulinism resulting from an absence of insulin receptor, acting through the IGF-1 receptor, causes HCM along with intrauterine growth restriction in Donahue syndrome. 72) Increased IGF-1 levels at the time of delivery are correlated with neonatal septal HCM in infants of mothers with diabetes. 73) 74) Reduced glucose uptake in the postnatal heart indicates that facilitated maturation of cardiomyocytes and high levels of glucose may inhibit maturation of cardiomyocytes at genetic, structural, metabolic, electrophysiological, and biomechanical levels by promoting excessive nucleotide biosynthesis through pentose phosphate phosphorylation.…”

Insulin Resistance: The Increased Risk of Cancers

“…Severe fasting hypoglycemia is the characteristic feature of the syndrome. Leprechaunism is also characterized by postprandial hyperglycemia, severe intrauterine growth restriction, postnatal growth failure, hypotonia, facial dysmorphism, and development delay [71][72][73].…”