Challenges in clinical diagnosis of williams-beuren syndrome in sub-saharan africans: case reports from cameroon

Abstract

Williams-Beuren syndrome (WBS) is a rare neurodevelopmental condition caused by a recurrent chromosomal microdeletion involving about 28 contiguous genes at 7q11.23. Most patients display a specific congenital heart defect, characteristic facial features, a particular behavior, and intellectual disability. Cases from sub-Saharan Africa have been seldom reported. The present study describes 3 Cameroonian patients affected by WBS, aged 19 months, 13 and 14 years, in whom the diagnosis was confirmed by fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH). The first patient presented with a congenital heart defect, the second and third with learning difficulties as well as developmental and behavioral issues. In the latter 2 cases, the facial phenotypes were similar to those of the unaffected population with the same ethnic background. However, the cardiovascular anomalies and friendly behavioral attitudes led to suspicion of WBS. FISH revealed the deletion of the WBS critical region in the first patient, and array-CGH detected a heterozygous ∼1.4-Mb deletion in the 7q11.23 region in the second and third patient. This preliminary report suggests that for sub-Saharan Africans clinical suspicion of WBS could be mostly based on behavioral phenotype and structural heart defects, and less on the classical facial dysmorphic signs.

Keywords: Cameroon; Clinical diagnosis; Sub-Saharan Africans; Williams-Beuren syndrome.

Fig. 1

Facial features of the 3 patients. a Front view of patient 1 at 19 months of age showing anteverted nares, long philtrum, bulbous nasal tip, and mild lower-lip fullness. b Front view of patient 2 at 13 years of age. Note broad forehead, flat nasal bridge, supraorbital fullness, bulbous nasal tip, downturned mouth, and full lips. c Front view of patient 3 at 14 years of age. Note supraorbital fullness, flat nasal bridge, bulbous nasal tip, wide mouth, and mild lower-lip fullness.

Fig. 2

Molecular cytogenetic results. a FISH result for patient 1. Metaphase FISH analysis with probes WBSCR9, LIMK1, CYLN2 labeled in red (Texas Red Spectrum). The arrows indicate both chromosomes 7, one showing no signal, confirming the WBS deletion in patient 1. b Array-CGH result in patients 2 and 3. Note a deletion of 1.4 Mb encompassing the region 7q11.23. Breakpoints were located between positions 72,726,578 and 74,139,331 bp (hg19) for both patient 2 and patient 3.