Details

Autor(en) / Beteiligte

• Bayat, Allan
• Lindau, Tobias
• Aledo‐Serrano, Angel
• Gil‐Nagel, Antonio
• Barić, Ivo
• Bartoniček, Dorotea
• Mateševac, Josipa
• Ramadža, Danijela Petković
• Žigman, Tamara
• Pušeljić, Silvija
• Dorner, Sanja
• Bupp, Caleb
• Devries, Seth
• Møller, Rikke Steensbjerre

Titel

GPI‐anchoring disorders and the heart: Is cardiomyopathy an overlooked feature?

Ist Teil von

• Clinical genetics, 2023-11, Vol.104 (5), p.598-603

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2023

Quelle

Wiley Online Library

Beschreibungen/Notizen

• Glycosylphosphatidylinositol anchoring disorders (GPI‐ADs) are a subgroup of congenital disorders of glycosylation. GPI biosynthesis requires proteins encoded by over 30 genes of which 24 genes are linked to neurodevelopmental disorders. Patients, especially those with PIGA‐encephalopathy, have a high risk of premature mortality which sometimes is attributed to cardiomyopathy. We aimed to explore the occurrence of cardiomyopathy among patients with GPI‐ADs and to raise awareness about this potentially lethal feature. Unpublished patients with genetically proven GPI‐ADs and cardiomyopathy were identified through an international collaboration and recruited through the respective clinicians. We also reviewed the literature for published patients with cardiomyopathy and GPI‐AD and contacted the corresponding authors for additional information. We identified four novel and unrelated patients with GPI‐AD and cardiomyopathy. Cardiomyopathy was diagnosed before adulthood and was the cause of early demise in two patients. Only one patients underwent cardiac workup after being diagnosed with a GPI‐AD. All were diagnosed with PIGA‐encephalopathy and three had a disease‐causing variant at the same residue. The literature reports five additional children with GPI‐AD related cardiomyopathy, three of which died before adulthood. We have shown that patients with GPI‐ADs are at risk of developing cardiomyopathy and that regular cardiac workup with echocardiography is necessary. Glycosylphosphatidylinositol anchoring disorders (GPI‐ADs) are complex neurodevelopmental syndromes with a high risk of premature mortality. We have shown that patients with GPI‐ADs are at risk of developing childhood‐onset cardiomyopathy; an overlooked and potentially fatal feature. We recommend regular cardiac workup with echocardiography once a genetic diagnosis of GPI‐AD is established.