Endokrine Ursachen eines intrauterinen Kleinwuchses

Zusammenfassung

Endokrine Ursachen eines intrauterinen Klein-wuchses galten bislang als sehr seltene monogene Krankheiten, klinisch von geringer Relevanz. Hierbei wurden bislang genetische Defekte des IGF-1-Gens und des IGF-1-Rezeptor (IGF1R)-Gens identifiziert. Während IGF-1-Genmutationen durch eine deutliche intrauterine und postnatale Wachstumsretardie-rung in Kombination mit einer psychomotorischen Retardierung und einer Innenohrschwerhörigkeit charakterisiert sind und homozygot vererbt werden, ist bei Patienten mit einer IGF1R-Mutation bis auf wenige Ausnahmen der Phänotyp auf eine Haploinsuffizienz für den Rezeptor zurückzuführen. Die steigende Anzahl nachgewiesener Mutationen in diesem Rezeptor verdeutlicht die Variabilität in der Ausprägung dieses Phänotyps und lässt vermuten, dass bei ca. 15 % aller Patienten mit einem intrauterinen Kleinwuchs, die IGFI-Serumspiegel im oberen Normbereich aufweisen, eine IGF1R-Mutation als Ursache der Wachstumsstörung nachweisbar ist. Eine differenzierte Untersuchung und langfristige klinische Verlaufsbeobachtung sind erforderlich, um die medizinische Versorgung dieser Patienten in Zukunft zu optimieren.

Summary

So far endocrine disorders as the origin of intrauterine growth retardation were considered to be very rare monogenetic disorders of limited clinical relevance. Genetic defects have been recognized within the IGF-1 and IGF-1 receptor (IGF1R) genes. Whereas IGF-1 gene mutations result in significant intrauterine and postnatal growth retardation in combination with psychomotor retardation and sensoneural deafness and are inherited homozygously, the phenotype of the patients with IGF1R mutations is the result of haploin-sufficiency for the receptor. The increasing number of documented mutations within this receptor shows the variability of the pheno-type and indicates that app. 15 % of all patients with intrauterine growth retardation and an IGF-I serum level in the upper normal range or above have an IGF1R mutation. At present a meticulous biochemical workup of each case and a long-term clinical follow up of all these patients seems necessary in order to optimize the medical care for these patients in future.

Schlüsselwörter

SGA - intrauterine Wachstumsverzögerung - IGF-I - IGF-1-Rezeptor

Keywords

SGA - intrauterine growth retardation - IGF-I - IGF-1 receptor

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