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
-
1
Neumann K, Keilmann A, Rosenfeld J. et al .
Sprachentwicklungsstörungen bei Kindern. Leitlinien der Deutschen Gesellschaft für Phoniatrie und Pädaudiologie.
Kindheit und Entwicklung.
2009;
18
(4)
222-231
-
2
Bishop DVM.
What causes specific language impairment in children?.
Current Directions in Psychological Science.
2006;
15
(5)
217-221
-
3
Stark R, Tallal P.
Selection of children with specific language deficits.
Journal of Speech and Hearing Disorders.
1981;
46
114-122
-
4 Grimm H. Störungen der Sprachentwicklung Göttingen: Hogrefe; 2002
-
5 Siegmüller J, Bartels H. Sprache – Sprechen – Stimme – Schlucken München: Elsevier; 2006
-
6 Schöler H, Fromm W, Kany W. Spezifische Sprachentwicklungsstörung und Sprachenlernen Heidelberg: Edition Schindele im Universitätsverlag C. Winter; 1998
-
7
Tomblin JB, Records NL, Buckwalter P. et al .
Prevalence of specific language impairment in kindergarten children.
Journal of Speech, Language, and Hearing Research.
1997;
40
1245-1260
-
8 Leonard LB. Children with specific language impairment Cambridge, MA: MIT Press; 2000
-
9
Conti-Ramsden G, Durkin K, Simkin Z. et al .
Specific language impairment and school outcomes. I: identifying and explaining variability at the end of compulsory education.
International Journal of Language and Communication Disorders.
2009;
44
(1)
15-35
-
10
Seemann MC.
Die Bedeutung der Zwillingspathologie für die Erforschung von Sprachleiden.
Sprach-Stimmheilkunde.
1937;
1
88
-
11 Bishop DVM. Specific language impairment, dyslexia, and autism: using genetics to unravel their relationship.. Hove: Psychology Press; 2008: 67-78
-
12
Stromswold K.
Genetics of spoken language disorders.
Human Biology.
1998;
70
293-320
-
13
Lewis BA, Thompson LA.
A study of developmental speech and language disorders in twins.
Journal of Speech and Hearing Research.
1992;
35
1086-1094
-
14
Bishop DVM, North T, Donlan C.
Genetic basis of specific language impairment: evidence from a twin study.
Developmental Medicine and Child Neurology.
1995;
37
56-71
-
15
Tomblin JB, Buckwalter PR.
Heritability of poor language achievement among twins.
Journal of Speech, Language and Hearing Research.
1998;
41
188-199
-
16
Stromswold K.
The genetics of speech and language impairments.
The New England Journal of Medicine.
2008;
359
(22)
2381-2383
-
17
Baddeley A, Gathercole S, Papagno C.
The phonological loop as a language learning device.
Psychological Review.
1998;
105
158-173
-
18
Bishop DVM, North T, Donlan C.
Nonwort repetition as a behavioural marker for inherited language impairment: Evidence from a twin study.
Journal of Child Psychology and Psychiatry.
1996;
37
56-71
-
19 Tallal P. Experimental studies of language learning impairments: From research to remediation.. Hove: Psychology Press; 2000: 131-155
-
20
Bishop DVM, Adams CV, Norbury CF.
Distinct influences on grammar and phonological short-term memory deficits: Evidence from 6-year-old twins.
Genes, Brain and Behavior.
2006;
5
158-169
-
21
Felsenfeld S, Plomin R.
Epidemiological and offspring analyses of developmental speech disorders using data from the Colorado Adoption Project.
Journal of Speech, Language and Hearing Research.
1997;
40
778-791
-
22
Lai CSL, Fisher SE, Hurst JA. et al .
A forkhead gene is mutated in a severe speech and language disorder.
Nature.
2001;
413
519-523
-
23
Newbury DF, Bonora E, Lam JA. et al .
FOXP2 is not a major susceptibility gene for autism or specific language impairment.
American Journal of Human Genetic.
2002;
70
60-71
-
24
Arnold GE.
The genetic background of developmental language disorder.
Folia Phoniatrica.
1961;
13
246-254
-
25 Newbury DF, Monaco AP. The application of molecular genetics to the study of developmental language disorder.. Hove: Psychology Press; 2008: 79-91
-
26
SLI Consortium (SLIC)
.
A genomwide scan identifies two novel loci involved in specific language impairment.
American Journal of Human Genetic.
2002;
70
384-389
-
27
Falcaro M, Pickles A, Newbury DF. et al .
Genetic and phenotypic effects of phonological short-term memory and grammatical morphology in specific language impairment.
Genes, Brain and Behavior.
2008;
7
1717-1720
-
28
SLI Consortium
.
Highly significant linkage to SLI1 locus in an expanded sample of individuals affected by Specific Language Impairment (SLI).
American Journal of Human Genetic.
2004;
94
1225-1238
-
29
Bartlett CW, Flax JF, Logue MW. et al .
A major susceptibility locus for specific language impairment is located on chromosome 13q21.
American Journal of Human Genetic.
2002;
71
45-55
-
30
Bishop DVM.
Genes, cognition and communication. Insights from neurodevelopmental disorders.
Annals of the New York Academy of Sciences.
2009;
1156
1-18
-
31
Vernes SC, Newbury DF, Abrahams BS. et al .
A functional genetic link between distinct developmental language disorders.
The New England Journal of Medicine.
2008;
359
2337-2345
-
32
Newbury DF, Fischer SE, Monaco AP.
Recent Advances in the genetics of language impairment.
Genome Medicine.
2010;
2
(1)
6
-
33
Zweier C, de Jong EK, Zweier M. et al .
CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila.
American Journal of Human Genetic.
2009;
85
(5)
655-666
-
34
Plomin R, Haworth CM, Davis OS.
Common disorders are quantitative traits.
Nature Reviews Genetics.
2009;
10
(12)
872-878
-
35
Plomin R, Kovas Y.
Generalist genes and learning disabilities.
Psychological Bulletin.
2005;
131
(4)
-
36
Barry JG, Yasin I, Bishop DV.
Heritable risk factors associated with language impairments.
Genes, Brain, and Behavior.
2007;
6
66-76
-
37
Clark A, O’Hare A, Watson J. et al .
Severe receptive language disorder in childhood – familial aspects and long-term outcomes: results from a Scottish study.
Archives of Disease in Childhood.
2007;
92
614-619
Korrespondenzadresse
Dr. med. J. Rosenfeld
Klinik für Audiologie und
Phoniatrie
Charité– Universitätsmedizin
Berlin
Augustenburger Platz 1
13353 Berlin
eMail: jochen.rosenfeld@charite.de
