Williams Syndrome. Development of a New Scoring System for Clinical Diagnosis

Abstract

OBJECTIVE:To develop a scoring system based on clinical findings to assist pediatricians in the diagnosis of William syndrome and to delineate when the fluorescent in-situ hybridization test to detect the microdeletion at 7q11.23 may be needed. METHODS:The fluorescent in-situ hybridization test was performed on 20 patients presenting William syndrome suggestive clinical features. Eleven studies were selected from the literature in which there were 2 groups: patients with positive or negative fluorescent in-situ hybridization tests. Forty-two clinical characteristics were compared to those reported in the literature to determine which ones were associated with the affected patients (ie, bearing deletions) using meta-analysis. The 2-tailed Fisher exact test were used so that the frequency of findings observed in fluorescent in-situ hybridization positive and fluorescent in-situ hybridization negative patients could be compared in the present study together with the patients from the literature. We developed a scoring system based on clinical findings and their significant associations with patients with positive fluorescent in-situ hybridization tests. From the mean and standard-deviation values of the data from our patients, we determined the cut-off score that that indicated the need for a fluorescent in-situ hybridization test to confirm diagnosis. RESULTS: Seventeen patients were fluorescent in-situ hybridization positive, and 3 were fluorescent in-situ hybridization negative. The more discriminative findings among fluorescent in-situ hybridization positive patients were the following: typical facies, low birth weight, feeding difficulties, constipation, supravalvar aortic stenosis, mental retardation, and friendly personality. The distribution of the points among the 20 patients ranged from 19 to 28 points with a mean value of 23.3 out of a possible total of 31 points. The cut-off score that indicated the need for a fluorescent in-situ hybridization test was 20. CONCLUSIONS: Our scoring system enables physicians to differentiate between those individuals who can be reliably diagnosed as having Williams syndrome solely from the clinical findings and those who need to undergo fluorescent in-situ hybridization testing for a correct diagnosis.

The common inversion of the Williams–Beuren syndrome region at 7q11.23 does not cause clinical symptoms

“…These findings underscore the importance of experienced clinical and psychological assessments in cases where a specific diagnosis is suspected, but the presentation is atypical. Obviously this is not always possible, but the development of syndrome-specific matrices for facial features [Hammond et al, 2005], growth parameters [Martin et al, 2007] cognitive or behavioral profiles [Mervis and Klein-Tasman, 2000] or for overall clinical presentation [Sugayama et al, 2007] should help with accurate diagnosis.…”

Short Communication Assessment of clinical scoring systems for the diagnosis of Williams-Beuren syndrome

“…Thus, the clinical diagnostic scoring systems proposed by Lowery et al (1995), AAP (2001), and Sugayama et al (2007) were used in 250 patients with WBS: 149 Brazilian patients [140 FISH (+) and 9 FISH (-)], and 101 patients from Argentina [88 FISH (+) and 13 FISH (-)]. Lowery et al (1995) reviewed the clinical findings for 110 patients with WBS confirmed by FISH, and developed a scoring system that classified WBS patients according to 6 different phenotypes.…”

“…The scoring system of Sugayama et al (2007) is based on a meta-analysis including 577 patients and 42 clinical signs. The cut-off score indicating the need for the FISH test is 20.…”

“…The American Academy of Pediatrics (AAP, 2001) recommends the use of a system that is based on the patient's score and indicates whether FISH should be performed. Sugayama et al (2007) developed a system in which a total score lower than "standard" points out the need for FISH testing to establish the diagnosis. Within this context, the scoring systems proposed by Lowery et al (1995), AAP (2001), and Sugayama et al (2007) were used in a group of patients from Brazil and Argentina with clinically suspected WBS, who had not undergone any kind of score-based evaluation or laboratory molecular testing.…”

“…Sugayama et al (2007) developed a system in which a total score lower than "standard" points out the need for FISH testing to establish the diagnosis. Within this context, the scoring systems proposed by Lowery et al (1995), AAP (2001), and Sugayama et al (2007) were used in a group of patients from Brazil and Argentina with clinically suspected WBS, who had not undergone any kind of score-based evaluation or laboratory molecular testing. The diagnostic accuracy of the clinical features of the scoring systems was compared with that of the gold standard, FISH test.…”