ESPE Abstracts (2023) 97 P1-331

1Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Hôpital Universitaire des Enfants Reine Fabiola (HUDERF), Paediatric Endocrinology Unit, Bruxelles, Belgium. 2Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Bruxelles, Belgium. 3Sorbonne Université, INSERM, UMR_S938 Centre de Recherche Saint Antoine, APHP, Hôpital Armand Trousseau, Explorations Fonctionnelles Endocriniennes, Paris, France

Hypomethylation of the ICR1 in 11p15 is the epigenetic alteration causing Silver Russel Syndrome (SRS) in over 50% of the patients. It is reported that 7-38% of SRS patients have multi-locus imprinting disturbance (MLID). MLID has been suggested to result from maternal mutations affecting the acquisition or maintenance of imprints. We report on a patient with MLID who presented with features of SRS and Temple syndrome in addition to severe 46 XY hypovirilisation, pseudohypoparathyroidism, hypertension, in a consanguineous family.

Clinical features
Full SRS features (Netchine criteria 5/6) BW 1450 (-4.8 SD), BL 37 cm (-6,3SD), BHC 34 cm (+0,05 SD)
Ambiguous genitalia (46 XY hypovirilization without mullerian remnant)
Temple Syndrome features: obesity, precocious puberty, intellectual deficit
Type 1B pseudohypoparathyroidism
Hypertension, Hypokalemia

Genetic analysis showed massive multilocus hypomethylation including loss of methylation of the telomeric region 11p15 (ICR1) confirming the diagnosis of Silver- Russel syndrome. Loss of methylation of the centromeric region 11p15.5 (ICR2) and other 12 regions were also found.

Discussion: We report on a patient with clinical features of SRS, Temple syndrome, PHP1B and 46 XY hypovirilization in the context of a massive multilocus hypomethylation. There are currently 10 reported imprinting disorders in humans. Hypospadias and/or cryptorchidism have occasionally been described in SRS patients. The reported patient has a mixed picture of gonadal dysgenesis (low AMH) and partial androgen insensitivity (high Testosterone, absent mullerian remnants). Modifications in the methylation pattern contribute to random transcriptional modifications that may give rise to either testicular dysgenesis or partial androgen insensitivity (androgen insensitivity has been associated to aberrant methylation of the Androgen Receptor promoter). Another possible explanation would be a distinct autosomal recessive condition causing to 46XY VSD in the context of consanguinity. This observation leads us to hypothesize that imprinting may influence the genital phenotype by modifying tissue-specific gene transcription.

Volume 97

61st Annual ESPE (ESPE 2023)

The Hague, Netherlands
21 Sep 2023 - 23 Sep 2023

European Society for Paediatric Endocrinology 

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