Multi-locus imprinting disturbance (MLID): interim joint statement for clinical and molecular diagnosis.

Background: Imprinting disorders are rare diseases resulting from altered expression of imprinted genes, which exhibit parent-of-origin-specific expression patterns regulated through differential DNA methylation. A subgroup of patients with imprinting disorders have DNA methylation changes at multiple imprinted loci, a condition referred to as multi-locus imprinting disturbance (MLID). MLID is recognised in most but not all imprinting disorders and is also found in individuals with atypical clinical features; the presence of MLID often alters the management or prognosis of the affected person.

Perinatal features of children with Silver-Russell syndrome due to 11p15 loss of methylation.

Background: A diagnosis of Silver-Russell syndrome (SRS), a rare imprinting disorder responsible for foetal growth restriction, is considered for patients presenting at least four criteria of the Netchine-Harbison clinical scoring system (NH-CSS). Certain items of the NH-CSS are not assessable until the age of 2 years. The objective was to determine perinatal characteristics of children with SRS to allow an early diagnosis.

Imprinting disorders.

Imprinting disorders (ImpDis) are congenital conditions that are characterized by disturbances of genomic imprinting. The most common individual ImpDis are Prader-Willi syndrome, Angelman syndrome and Beckwith-Wiedemann syndrome. Individual ImpDis have similar clinical features, such as growth disturbances and developmental delay, but the disorders are heterogeneous and the key clinical manifestations are often non-specific, rendering diagnosis difficult.

: Development, Genetic and Epigenetic Abnormalities.

In the 30 years since the first report of parental imprinting in insulin-like growth factor 2 () knockout mouse models, we have learnt much about the structure of this protein, its role and regulation. Indeed, many animal and human studies involving innovative techniques have shed light on the complex regulation of expression. The physiological roles of IGF-II have also been documented, revealing pleiotropic tissue-specific and developmental-stage-dependent action.

Height and body mass index in molecularly confirmed Silver-Russell syndrome and the long-term effects of growth hormone treatment.

Objective: Silver-Russell syndrome (SRS) causes short stature. Growth hormone (GH) treatment aims to increase adult height. However, data are limited on the long-term outcomes of GH in patients with molecularly confirmed SRS.

Screening of patients born small for gestational age with the Silver-Russell syndrome phenotype for DLK1 variants.

Silver-Russell syndrome (SRS) is a rare imprinting disorder associated with prenatal and postnatal growth retardation. Loss of methylation (LOM) on chromosome 11p15 is observed in 40 to 60% of patients and maternal uniparental disomy (mUPD) for chromosome 7 (upd(7)mat) in ~5 to 10%. Patients with LOM or mUPD 14q32 can present clinically as SRS.

Demographic Characteristics, Risk Factors, and Presenting Features of Children with Symptomatic Nutritional Rickets: A French Series.

Aim: To describe the demographic characteristics, risk factors, and presenting features of children with symptomatic nutritional rickets in France.

Methods: This is a retrospective study of 38 children diagnosed with nutritional rickets from 1998 to 2019.

Results: We observed a higher frequency of rickets in males (74 vs.

Sleep disordered breathing in Silver-Russell syndrome patients: a new outcome.

Objective: Imprinting disorders (ID), such as Prader-Willi syndrome (PWS), are associated with sleep-disordered breathing (SDB). No data are available for Silver-Russell syndrome (SRS), another ID that shares clinical features with PWS, although many patients describe excessive daytime sleepiness, disturbed sleep, and snoring. The aim of this study was to characterize sleep in children with SRS and to evaluate the impact of recombinant growth hormone (rGH) therapy.

Increasing knowledge in defects: lessons from 35 new patients.

Background: The type 1 insulin-like growth factor receptor (IGF1R) is a keystone of fetal growth regulation by mediating the effects of IGF-I and IGF-II. Recently, a cohort of patients carrying an defect was described, from which a clinical score was established for diagnosis. We assessed this score in a large cohort of patients with identified defects, as no external validation was available.

Roles of Type 1 Insulin-Like Growth Factor (IGF) Receptor and IGF-II in Growth Regulation: Evidence From a Patient Carrying Both an 11p Paternal Duplication and 15q Deletion.

We report an original association of complex genetic defects in a patient carrying both an 11p paternal duplication, resulting in the double expression of , as reported in Beckwith-Wiedemann syndrome, and a 15q terminal deletion, including the (), resulting in haploinsufficiency for this gene. The patient was born with measurements appropriate for her gestational age but experienced growth retardation in early childhood, allowing a better comprehension of the IGF system in the pathophysiology of growth. It is possible that IGF-II plays a key role in fetal growth, independently of IGF1R signaling, and that its role is less important in post-natal growth, leaving IGF-I and growth hormone as the main actors.

Overgrowth syndromes - clinical and molecular aspects and tumour risk.

Overgrowth syndromes are a heterogeneous group of rare disorders characterized by generalized or segmental excessive growth commonly associated with additional features, such as visceromegaly, macrocephaly and a large range of various symptoms. These syndromes are caused by either genetic or epigenetic anomalies affecting factors involved in cell proliferation and/or the regulation of epigenetic markers. Some of these conditions are associated with neurological anomalies, such as cognitive impairment or autism.

Transcriptional profiling at the domain explains clinical overlap between imprinting disorders.

Imprinting disorders (IDs) often affect growth in humans, leading to diseases with overlapping features, regardless of the genomic region affected. IDs related to hypomethylation of the human 14q32.2 region and its domain are associated with Temple syndrome (TS14).

Diagnosis and management of postnatal fetal growth restriction.

Fetal growth restriction (FGR) can result from multiple causes, such as genetic, epigenetic, environment, hormonal regulation, or vascular troubles and their potential interaction. The physiopathology of FGR is not yet fully elucidated, but the insulin-like growth factor system is known to play a central role. Specific clinical features can lead to the identification of genetic syndromes in some patients.

Chromosome 14q32.2 Imprinted Region Disruption as an Alternative Molecular Diagnosis of Silver-Russell Syndrome.

Context: Silver-Russell syndrome (SRS) (mainly secondary to 11p15 molecular disruption) and Temple syndrome (TS) (secondary to 14q32.2 molecular disruption) are imprinting disorders with phenotypic (prenatal and postnatal growth retardation, early feeding difficulties) and molecular overlap.

Objective: To describe the clinical overlap between SRS and TS and extensively study the molecular aspects of TS.

Chromosomal rearrangements in the 11p15 imprinted region: 17 new 11p15.5 duplications with associated phenotypes and putative functional consequences.

Background: The 11p15 region contains two clusters of imprinted genes. Opposite genetic and epigenetic anomalies of this region result in two distinct growth disturbance syndromes: Beckwith-Wiedemann (BWS) and Silver-Russell syndromes (SRS). Cytogenetic rearrangements within this region represent less than 3% of SRS and BWS cases.

Imprinted disorders and growth.

Fetal growth is a complex process. Its restriction is associated with morbidity and long-term metabolic consequences. Imprinted genes have a critical role in mammalian fetal growth.

Diagnosis and management of Silver-Russell syndrome: first international consensus statement.

This Consensus Statement summarizes recommendations for clinical diagnosis, investigation and management of patients with Silver-Russell syndrome (SRS), an imprinting disorder that causes prenatal and postnatal growth retardation. Considerable overlap exists between the care of individuals born small for gestational age and those with SRS. However, many specific management issues exist and evidence from controlled trials remains limited.

New clinical and molecular insights into Silver-Russell syndrome.

Purpose Of Review: The purpose of review is to summarize new outcomes for the clinical characterization, molecular strategies, and therapeutic management of Silver-Russell syndrome (SRS).

Recent Findings: Various teams have described the clinical characteristics of SRS patients by genotype. A clinical score for the definition of SRS and for orienting molecular investigations has emerged.

Models for predicting the adult height and age at first menstruation of girls with idiopathic central precocious puberty.

Background: It is difficult to determine whether to treat a given girl who has idiopathic central precocious puberty (CPP) with gonadotropin-releasing hormone analog (GnRHa) in terms of adult height (AH). The objective was to provide an easy tool for predicting AH and age at first menstruation at initial evaluation to help guide the decision regarding whether to treat.

Methods: Data analysis using multiple linear regression models was performed in 134 girls with CPP.

Premature pubarche before one year of age: distinguishing between mini-puberty variants and precocious puberty.

Background: The aim of this study was to facilitate the distinction between the benign "mini-puberty of early infancy" and precocious puberty (PP).

Material And Methods: We compared 59 patients (21 boys and 38 girls) seen for pubic hair development before one year of age diagnosed as mini-puberty to 13 patients (2 boys) in whom pubertal development before one year revealed a PP.

Results: The boys with mini-puberty presented with pubic hair development and prepubertal testicular volume, with low plasma testosterone concentrations.

Presentation of 493 consecutive girls with idiopathic central precocious puberty: a single-center study.

Background: Despite the number of reported data concerning idiopathic central precocious puberty (CPP) in girls, major questions remain including its diagnosis, factors, and indications of gonadotropin releasing hormone (GnRH) analog treatment.

Methods: A retrospective, single-center study was carried out on 493 girls with CPP.

Results: Eleven girls (2.