biochimica clinica

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Biochimica Clinica 2012; 36(3) 187-192

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Nuovi approcci diagnostici al ritardo mentale

AUTORI

Elisa Danese1, Emanuela Meneghelli1, Fiorenza Aprili1, Martina Montagnana1, Orsetta Zuffardi2, Leonardo Zoccante3, Bernardo Dalla Bernardina3, Gian Cesare Guidi1
1Dipartimento di Scienze della Vita e della Riproduzione, Sezione di Biochimica Clinica, Verona
2Dipartimento di Patologia Umana ed Ereditaria, Fondazione IRCCS Mondino, Pavia
3Dipartimento di Scienze della Vita e della Riproduzione, Sezione di Neuropsichiatria Infantile, Verona

ABSTRACT

New diagnostic approaches to mental retardation

Genomic imbalances are considered the most frequent causes of mental retardation (MR). Although widespread screening with novel molecular karyotyping methods, such as multiplex ligation-dependent probe amplification (MLPA) and array-based comparative genomic hybridization (Array-CGH) might be desirable, effective clinical preselection is essential because of the technical complexities and cost of testing. This study focuses on a retrospective analysis of clinical features in patients with MR of unknown etiology,thereby assessing the sensitivity of a six item checklist in identifying rearranged subjects. The diagnostic powers of single techniques were also evaluated. We studied 164 subjects with MR who had completed the follow diagnostic process: karyotype and eventually fluorescence in situ hybridization (FISH) in case of suspected microdeletion syndrome, specific analysis in case of suspected X-linked or monogenic disease, MLPA for subtelomeric rearrangements in patients negative to previous tests, Array-CGH in patients negative to MLPA. A six items checklist based on relevant clinical signs was retrospectively applied. 5 patients were carrier of chromosomal abnormalities (3 detected by karyotype and 2 by FISH), 3 were affected by X-fragile syndrome, 6 had mutations, and 33 were carriers of genomic imbalances (9 detected by MLPA and 24 by Array-CGH), while 117 resulted negative to any tests. In patients with genomic imbalances and in subjects without rearrangements the median score of the checklist was 6 (range 3-9) and 4 (range 0-8), respectively (P <0,0001). The ROC analysis for the diagnostic accuracy of our checklist showed an area under the curve of 0.74 (95% confidence interval: 0.65-0.83). Using a cut-off for the score of U3, 24% of patients could have been excluded without missing any genomic imbalances. This study supports the evidence that the application of a clinical checklist may improve the rate of pathological findings in patients with MR.

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