Imprinting disorders

Imprinting disorders are a group of rare congenital conditions caused by disruptions in genomic imprinting, a process by which certain genes are expressed in a parent-of-origin-specific manner. Normally, for imprinted genes, only one copy (either the maternal or paternal allele) is active. When this tightly regulated epigenetic mechanism is disturbed — through deletions, uniparental disomy, mutations in imprinting control centers, or epimutations — the resulting imbalance in gene expression leads to disease. Imprinting disorders as a group (Orphanet code 641343) encompass several well-characterized conditions including Beckwith-Wiedemann syndrome, Silver-Russell syndrome, Prader-Willi syndrome, Angelman syndrome, Temple syndrome, Kagami-Ogata syndrome, pseudohypoparathyroidism, and transient neonatal diabetes mellitus, among others. These disorders affect multiple body systems depending on the specific genomic region involved. Common clinical features across the group include abnormalities of growth (either overgrowth or growth restriction), neurodevelopmental impairment, intellectual disability, metabolic disturbances, and endocrine dysfunction. Some imprinting disorders are associated with increased tumor risk (e.g., Wilms tumor in Beckwith-Wiedemann syndrome), while others primarily affect neurological function (e.g., severe intellectual disability and seizures in Angelman syndrome) or metabolic regulation (e.g., hyperphagia and obesity in Prader-Willi syndrome). Many present at birth or in early infancy with features such as abnormal birth weight, feeding difficulties, hypotonia, or neonatal diabetes. There is no curative treatment for imprinting disorders as a group. Management is largely supportive and symptom-specific, including growth hormone therapy for growth-restricted conditions like Silver-Russell syndrome, multidisciplinary management of obesity and behavioral issues in Prader-Willi syndrome, anti-seizure medications in Angelman syndrome, and tumor surveillance in Beckwith-Wiedemann syndrome. Early diagnosis through molecular genetic and epigenetic testing is important for appropriate management, genetic counseling, and recurrence risk assessment. Research into targeted epigenetic therapies is ongoing but remains largely experimental.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Imprinting disorders