Genetische Faktoren bei spezifischer Sprachentwicklungsstörung

Zusammenfassung

Als spezifische Sprachentwicklungsstörung (SSES, Synonym: Umschriebene Sprachentwicklungsstörung, USES) bezeichnet man eine primäre, isolierte Entwicklungsstörung der Sprache ohne offensichtlich erkennbaren Grund, d. h. ohne dominierende Hörstörungen, globale Entwicklungsstörungen oder andere komorbide Krankheiten. In Familienaggregations- und Zwillingsstudien konnte eine hohe Erblichkeit dieser Beeinträchtigung nachgewiesen werden. Die meisten Stammbaumanalysen zeigen kein „mendelndes” Vererbungsmuster und passen nicht zu einem einzelnen Gendefekt. Über die letzten Jahre haben sich die Hinweise einer multifaktoriellen Ätiologie der SSES verdichtet, bei der der Phänotyp wie bei vielen komplexen Merkmalen von mehreren Genen beeinflusst wird, die untereinander und mit der Umwelt interagieren. In molekulargenetischen Studien konnten bisher 4 Genorte für die SSES eingegrenzt werden (SLI1–SLI4). Als erstes Gen mit Bezug zur SSES wurde CNTNAP2 auf Chromosom 7 identifiziert, das bei der neuronalen Entwicklung des menschlichen Gehirns eine Rolle spielt. Polymorphismen in diesem Gen zeigten eine Assoziation mit Einschränkungen beim „Wiederholen von Nichtwörtern” als Ausdruck des phonologischen Kurzzeitgedächtnisses. In dem vorliegenden Schwerpunktartikel werden verschiedene Studientypen zur SSES systematisch dargestellt und genetische Erkenntnisse, die eine multifaktorielle Ätiologie belegen, erläutert.

Abstract

The term “specific language impairment” (SLI) is used for a primary, specific developmental disorder of language without any obvious reason, e. g., hearing disorders or other developmental delay. Family aggregation and twin studies have demonstrated that SLI is a highly heritable disorder. Most pedigrees do not show Mendelian inheritance and are not consistent with a single gene defect. Over the past years, evidence had been gathered that the etiology of SLI is multifactorial and that the phenotype is influenced by numerous of genes which interact both with one another and with the environment, as it is the case with many other complex traits. Up to today, linkage analyses of SLI have identified 4 gene regions (SLI1–SLI4). CNTNAP2 on chromosome 7 which plays a role in the neuronal development of the human cortex was identified as the first gene with an association to SLI. Polymorphisms of this gene showed significant associations with poor non-word repetition as a marker of phonological short-term memory. In the present review, we describe different types of methods and study designs to provide evidence for the genetic influence of specific language impairment. Several reasons are discussed to show that SLI is not a distinct disorder, but rather the extreme end of a normal distribution of language ability, likely to be influenced by multiple genetic and environmental influences of small effect.

Schlüsselwörter

Gene - genetische Faktoren - spezifische Sprachentwicklungsstörung (SSES) - Ätiologie

Key words

genes - genetic factors - specific language impairment (SLI) - etiology

Literatur

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