ESPE Abstracts

Background: The association between nutrition and growth is common knowledge but the mechanism is still unelucidated. Several reported cases in the literature describe growth without GH, that in most cases were associated with obesity, suggesting, that the adipocytes might have a role in regulating linear growth.Objective and hypotheses: The aim of the study was to search for a skeletal growth factor that is secreted by adipocytes....

Introduction: Mutations in the GH1 promoter are a rare cause of isolated GH deficiency (IGHD). In order to find the molecular cause of short stature due to IGHD, three siblings (2 M) born to consanguineous parents without mutations in the GHRHR and GH1 coding regions were screened for mutations in the GH1 promoter and locus control region. All patients harbored two variants (c.−123T>C and −161C>T) in homozygous state in the GH1 promoter, not found in 100 co...

Background: Multiple organ dysfunction occurs in mitochondrial diseases (MDs). MDs are sometimes difficult to diagnose, because patients have solitary and/or combination of various symptoms including short stature, diabetes, myopathy, and seizure. Since plasma levels of lactate and pyruvate are not always the perfect biomarker for MDs, there are many pseudo-mitochondrial patients who are suspect for MDs. Diagnosis for MDs often requires muscle biopsy, gene analysis, and measur...

Background: Heterozygous mutations in the IGF1 receptor (IGF1R) are often associated with congenital IGF1 resistance, causing variable degrees of intrauterine growth retardation (IUGR) and postnatal short stature. To date, only one homozygous IGF1R mutation has been reported, in a child presenting with severe growth failure, mild intellectual impairment, microcephaly, dysmorphic features, and cardiac malformations.Objective: We now repo...

Background: IGF1R gene mutations have been associated with varying degrees of intrauterine and postnatal growth retardation, and microcephaly. We have previously reported three novel variants in the IGF1R gene: de novo p.Arg1256Ser, de novo p.Asn359Tyr and p.Tyr865Cys (ENDO 2013, OR20-2).Aim: To characterize the functional effects of the novel IGF1R gene allelic variants.Methods: In ...

Background: GH insensitivity is caused by disturbances of GH receptor function or inability to transduce the hormone signal. Affected children are severely growth retarded and may also present immune complications when the transducer STAT5B is defective. Only autosomal-recessive STAT5B mutations have been described to date.Clinical case: Two male 14.5 year monozygotic twins presented with heights of 131.5 cm (−5.3 SDS). Bone age of the ind...

Background: Primary IGF1 deficiency (PIGFD) is a rare disease defined by low IGF1 levels, GH sufficiency and absence of secondary causes of growth failure. Whereas some members of the GH–IGF axis have been shown to be implicated in the severe syndromic forms of PIGFD due to GH insensitivity, genetic causes of less severely affected patients are mostly unknown.Objective and hypotheses: The aim of the present study was to systematically investigate fr...

Background: Cardiofaciocutaneous syndrome (CFCS) is a rare autosomal dominant (AD) condition characterized by cardiac abnormalities, a distinctive craniofacial appearance and short stature. Endocrine manifestations include GH deficiency and precocious puberty. CFCS is part of the RASopathy group including Noonan, LEOPARD, and Costello syndromes. The four associated genes are BRAF (~75%), MAP2K1 and MAP2K2 (~25%), and KRAS (<2%). Most individuals represent new sporadic muta...

Background: Prenatal growth restraint associates with increased oxidative stress – as judged by mitochondrial dysfunction – in pregnancies complicated by preeclampsia or diabetes, but it is uncertain whether this is also the case in uncomplicated pregnancies.Objective and hypotheses: To assess the link between fetal growth restraint and placental mitochondrial dysfunction, as reflected by changes in mitochondrial DNA content and superoxide dism...

Background: Small for gestational age (SGA), defined as ≤−2.0 SDS birth length or weight, is a condition seen in up to 3% of all newborn. Most SGA children catch up height in postnatal life. In a significant number (~10%), however, height remains below the third centile. Recombinant GH therapy is indicated when growth failure continues to 4 years of age. The pathophysiological basis of SGA is complex: monogenic disorders and/or fetal programming by environmental fa...

Background: SHOX and enhancer regions on PAR1 disorders have variable phenotypic consequences such as idiopathic short stature (ISS) and Leri-Weill Dyschondrosteosis (LWD).Objective and hypotheses: The aim of this observational multicentric study was to describe phenotypes and genotypes of a large population with mutation on SHOX and adjacent regions and to identify a possible phenotype–genotype correlation.M...

Background: Growth is a multifactorial process involving genetic, nutritional and other environmental determinants. Because of a major proportion of ultimate stature is dependent upon an intact GH and IGF1 axis, much attention has been devoted to abnormalities related to these growth factors and their signalling pathways.Objective and hypotheses: At the tissue level, the action of GH result from the interaction of GH with a specific cell surface GH recep...

Background: The short stature homeobox-containing (SHOX) gene, located in the telomeric pseudoautosomal region 1 (PAR1) on the short arm of both sex chromosomes, is important for linear growth.Objective and hypotheses: The aim of our study was to evaluate the presence of SHOX gene deletions/point mutations in children with short stature in order to understand the role of SHOX gene in idiopathic short stature (ISS) and estimate its frequency.<p class=...