Fig. 1

Suggested multi-locus testing algorithm for imprinting disorders. ¹The decision on first-line test depends on the clinical phenotype of the patient, consensus guidelines and national regulations. For some disorders and phenotypes, single-locus testing might be preferred; for some clinical indications (e.g. relatively non-specific growth restriction, hypotonia or developmental problems or features characteristic of more than one imprinting disorder) multi-locus testing may be preferred. Reproductive and family history may also be considered. ²MLID testing should be considered in case of clinical features reminiscent for SRS, BWS, TNDM and PHP. ³Differential diagnosis or alternative testing may include NGS-based genomic medicine, microarray, testing of alternative tissues or additional epigenetic analysis, depending on the clinical features of the patient. ⁴Depending on the disorder, national regulations and clinical consensus guidelines, positive reports may also include recommendations for further action such as additional analyses to identify the underlying molecular cause (e.g. discrimination between UPD and ID, exclusion of a Robertsonian translocation in case of a UPD for PWS, AS, TS14, KOS14) to estimate the recurrence risk, clinical management and counselling. ⁵Second-line testing may include NGS-based genomic analysis, detection of cis acting SNV or CNV, detection of trans acting variants, or other analyses pursuant to relevant consensus guidelines or the molecular change detected