Clinical score of 62 Italian patients with Cornelia de Lange syndrome and correlations with the presence and type of NIPBL mutation

• Published in: Clinical genetics Vol. 72; no. 2; pp. 98 - 108
• Main Authors: Selicorni, A, Russo, S, Gervasini, C, Castronovo, P, Milani, D, Cavalleri, F, Bentivegna, A, Masciadri, M, Domi, A, Divizia, MT, Sforzini, C, Tarantino, E, Memo, L, Scarano, G, Larizza, L
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2007; Blackwell
• Subjects: Adolescent; Adult; Biological and medical sciences; Child; Child, Preschool; clinical score; Cohort Studies; Cornelia de Lange syndrome; De Lange Syndrome - diagnosis; De Lange Syndrome - genetics; De Lange Syndrome - pathology; DNA Mutational Analysis; Female; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetics of eukaryotes. Biological and molecular evolution; genotype; Humans; Infant; Italy; Male; Malformations of the nervous system; Medical genetics; Medical sciences; Middle Aged; Molecular and cellular biology; Mutation; Neurology; NIPBL mutation; phenotype correlation; Prevalence; Proteins - genetics; Italy; Human; Cornelia de Lange syndrome; Nervous system diseases; Correlation; De Lange syndrome; Italian; Typing; genotype-phenotype correlation; Genotype; Patient; Cerebral disorder; clinical score; Phenotype; NIPBL mutation; Malformation; Central nervous system disease; Genetics; Mutation
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2007.00832.x

Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder characterized by facial dysmorphisms, upper limb abnormalities, growth and cognitive retardation. About half of all patients with CdLS carry mutations in the NIPBL gene. The first Italian CdLS cohort involving 62 patients (including 4 related members) was screened for NIPBL mutations after a clinical evaluation using a quantitative score that integrates auxological, malformation and neurodevelopmental parameters. The patients were classified as having an overall ‘severe’, ‘moderate’ or ‘mild’ phenotype. NIPBL screening showed 26 mutations so classified: truncating (13), splice‐site (8), missense (3), in‐frame deletion (1) and regulatory (1). The truncating mutations were most frequently found in the patients with a high clinical score, whereas most of the splice‐site and all missense mutations clustered in the low‐medium score groups. The NIPBL‐negative group included patients covering the entire clinical spectrum. The prevalence of a severe phenotype in the mutated group and a mild phenotype in the non‐mutated group was statistically significant. In terms of the isolated clinical signs, the statistically significant differences between the mutation‐positive and mutation‐negative individuals were pre‐ and post‐natal growth deficits, limb reduction, and delayed speech development. The proposed score seems to be a valuable means of prioritizing the patients with CdLS to undergo an NIPBL mutation test.