Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 29 S16.2

ICEECE2012 Symposia Understanding growth (3 abstracts)

Genes and the investigation of idiopathic short stature (ISS): are we ready for prime time?

J. Wit


Leiden University Medical Center, Leiden, The Netherlands.


Strictly speaking, the diagnosis of idiopathic short stature (ISS) can only be made after exclusion of all known causes of growth failure, but for pragmatic and financial reasons there are limits to the investigations that can be carried out. Clinical algorithms can assist decisions on genetic testing. Testing for SHOX is indicated if there are signs of Leri-Weill syndrome, including Madelung deformity, short forearm and lower legs. Short upper arms and legs should lead to testing for FGFR3 (hypochondroplasia). In both disorders sitting height/height ratio is high, and arm span/height ratio low. If serum IGF-I is <−2 SDS while the GH peak in a provocation tests is normal or high, the differential diagnosis includes 3 conditions with normal GH sensitivity (bioinactive GH; neurosecretory dysfunction; GHSR defect) and 4 conditions with low GH sensitivity (GHR, STAT5b, IGFALS and IGF1 defects). The likelihood of such defects can be assessed by measuring GHBP, IGFBP-3, prolactin, and ALS, and performing an IGF-I generation test. While all cases with homozygous IGF1 mutations are born small for gestational age (SGA) and microcephalic, heterozygous carriers can present as ISS, particularly in short families. Children with heterozygous IGF1R defects, usually characterized by a serum IGF-I>0 SDS, SGA and low head circumference, but in some cases birth weight and length are >−2 SDS (thus ‘ISS’). In cases with dysmorphic features, consulting a clinical geneticist is indicated. If a known genetic disorder is suspected, the candidate gene approach may lead to the diagnosis. If not, particularly if there are additional clinical features, a whole genome SNP analysis can be performed to detect copy number variants or uniparental disomy. With nextgen whole exome sequencing novel gene defects can be discovered, particularly if more than one family member is affected, or when various patients with a similar clinical syndrome are studied.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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