Radiographic Evaluation of Children with Growth Disorders

Kant, Sarina G.; Grote, F K; Ru, Minke H. de; Oostdijk, Wilma; Zonderland, Harmine M.; Breuning, Martijn H.; Wit, Jan M.

doi:10.1159/000108399

Cited by 18 publications

(10 citation statements)

References 55 publications

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“…The length of upper and lower arms and legs, and hands and feet, should be at least visually assessed, and possibly measured and compared with normative charts (a relatively short upper arm and leg is called rhizomelia, in contrast to mesomelia if forearm and lower leg are relatively short). A series of skeletal radiographs usually gives important clues for the diagnosis (15,102,103,104). Most forms of skeletal dysplasia show shortlimb dwarfism, in contrast to type I and II collagenopathies which are characterized by short-trunk dwarfism (14).…”

Section: Genetic Defects Affecting Paracrine Factors In the Gpmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

Wit

Oostdijk

Losekoot

et al. 2016

European Journal of Endocrinology

154

132

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The fast technological development, particularly single nucleotide polymorphism array, array-comparative genomic hybridization, and whole exome sequencing, has led to the discovery of many novel genetic causes of growth failure. In this review we discuss a selection of these, according to a diagnostic classification centred on the epiphyseal growth plate. We successively discuss disorders in hormone signalling, paracrine factors, matrix molecules, intracellular pathways, and fundamental cellular processes, followed by chromosomal aberrations including copy number variants (CNVs) and imprinting disorders associated with short stature. Many novel causes of GH deficiency (GHD) as part of combined pituitary hormone deficiency have been uncovered. The most frequent genetic causes of isolated GHD are GH1 and GHRHR defects, but several novel causes have recently been found, such as GHSR, RNPC3, and IFT172 mutations. Besides well-defined causes of GH insensitivity (GHR, STAT5B, IGFALS, IGF1 defects), disorders of NFkB signalling, STAT3 and IGF2 have recently been discovered. Heterozygous IGF1R defects are a relatively frequent cause of prenatal and postnatal growth retardation. TRHA mutations cause a syndromic form of short stature with elevated T 3 /T 4 ratio. Disorders of signalling of various paracrine factors (FGFs, BMPs, WNTs, PTHrP/IHH, and CNP/NPR2) or genetic defects affecting cartilage extracellular matrix usually cause disproportionate short stature. Heterozygous NPR2 or SHOX defects may be found in w3% of short children, and also rasopathies (e.g., Noonan syndrome) can be found in children without clear syndromic appearance. Numerous other syndromes associated with short stature are caused by genetic defects in fundamental cellular processes, chromosomal abnormalities, CNVs, and imprinting disorders.

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Section: Genetic Defects Affecting Paracrine Factors In the Gpmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

Wit

Oostdijk

Losekoot

et al. 2016

European Journal of Endocrinology

154

132

View full text Add to dashboard Cite

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“…Various guidelines for radiographic analysis of disproportionate short stature are available. They had recently been summarized by Kant et al [33] and based upon this review a recommendation for radiographic analysis was made (table 4). Results of this radiographic analysis can guide targeted molecular DNA analysis and can contribute to an efficient approach to diagnosing growth disorders.…”

Section: Diagnostic Proceduresmentioning

confidence: 99%

“…If such a syndrome is suspected, the pediatrician, in collaboration with the clinical geneticist, may consider targeted DNA analysis. For a systematic diagnostic approach we refer to a review by Kant et al [33], in which an overview of the different genetic causes of short stature is given, and a flow chart for molecular analyses is proposed. For a recent review on the diagnostic procedures to detect genetic disorders in the growth hormone-insulin-like growth factor I axis we refer to the paper by Walenkamp and Wit [35].…”

Section: Diagnostic Proceduresmentioning

confidence: 99%

Diagnostic Approach in Children with Short Stature

et al. 2009

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For early detection of pathological causes of growth failure proper referral criteria are needed, as well as a thorough clinical, radiological and laboratory assessment. In this minireview we first discuss the two consensus-based and one evidence-based guidelines for referral that have been published. The evidence-based guidelines result in a sensitivity of approximately 80% at a false-positive rate of 2%. Then, relevant clues from the medical history and physical examination are reviewed, and specific investigations based on clinical suspicion listed. In the absence of abnormal clinical findings, an X-ray of the hand/wrist and a laboratory screen are usually performed. Scientific evidence for the various components of laboratory screening is scarce, but accumulated experience and theoretical considerations have led to a list of investigations that may be considered until more evidence is available.

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“…In approximately 80% of children who are referred to a pediatric clinic because of short stature, no definite cause can be established, even after a thorough diagnostic workup including extensive biochemical screening and radiologic investigations [1,2,3,4]. Such children are usually classified as idiopathic short stature (ISS) [1].…”

Section: Introductionmentioning

confidence: 99%

Genetic Analysis of Short Children with Apparent Growth Hormone Insensitivity

Wit

Duyvenvoorde²,

Scheltinga³

et al. 2012

Horm Res Paediatr

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Background/Aims: In short children, a low IGF-I and normal GH secretion may be associated with various monogenic causes, but their prevalence is unknown. We aimed at testing GH1, GHR, STAT5B, IGF1, and IGFALS in children with GH insensitivity. Subjects and Methods: Patients were divided into three groups: group 1 (height SDS <–2.5, IGF-I <–2 SDS, n = 9), group 2 (height SDS –2.5 to –1.9, IGF-I <–2 SDS, n = 6) and group 3 (height SDS <–1.9, IGF-I –2 to 0 SDS, n = 21). An IGF-I generation test was performed in 11 patients. Genomic DNA was used for direct sequencing, multiplex ligation-dependent probe amplification and whole-genome SNP array analysis. Results: Three patients in group 1 had two novel heterozygous STAT5B mutations, in two combined with novel IGFALS variants. In groups 2 and 3 the association between genetic variants and short stature was uncertain. The IGF-I generation test was not predictive for the growth response to GH treatment. Conclusion: In severely short children with IGF-I deficiency, genetic assessment is advised. Heterozygous STAT5B mutations, with or without heterozygous IGFALS defects, may be associated with GH insensitivity. In children with less severe short stature or IGF-I deficiency, functional variants are rare.

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Radiographic Evaluation of Children with Growth Disorders

Cited by 18 publications

References 55 publications

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

Diagnostic Approach in Children with Short Stature

Genetic Analysis of Short Children with Apparent Growth Hormone Insensitivity

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