IllnessWilliams-Beuren syndrome, differential diagnosis

AFTER EXCLUSION of the 7q11.23 deletion

NGS +

[Sanger]

Williams-Beuren syndrome (WBS) is a developmental disorder characterized by mild to moderate mental retardation/learning problems, unique personality traits, distinctive facial features and cardiovascular problems. Patients typically have difficulty with visuospatial tasks but have good spoken language, music and learning through repetition. Affected individuals are outgoing, have engaging personalities, and show great interest in others. Attention deficit disorder, anxiety, and phobias are common. Young children have pronounced facial features with a broad forehead, partially swollen eye areas, flat bridge of the nose, full cheeks, small chin, and dental problems. Older children and adults typically have a longer face with a wide mouth and full lips. Stenosis of the supravalvular aorta and narrowing of the pulmonary and coronary arteries are common. Hypertension, hardened blood vessels, and increased risk of anesthesia have been reported. Additional symptoms include joint problems, loose skin and hypercalcemia in infancy, developmental delays, problems with coordination and short stature. Medical problems involving vision or hearing, hyperacusis are frequently associated. Problems with the digestive tract are also possible. Obesity or diabetes can develop in adulthood. WBS is caused by de novo 1.5- to 1.8-Mb 7q11.23 deletions which include mostly >24 genes. Rarely, people with WBS inherit the deletion from an affected parent as an autosomal dominant trait. The ELN, GTF2I, GTF2IRD1 and LIMK1 genes are typically deleted. Presence or absence of the NCF1 gene impacts of developing hypertension. Postnatally the molecular (cyto-)genetic diagnostic yield approaches 100%, especially in typical cases.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1249/

• Nomencl.: Williams s. due to recurrent 7q11.23 contiguous gene deletion of the WBS critical region
• Alias: Beuren syndrome
• Alias: Elfin facies syndrome
• Alias: Elfin facies with hypercalcemia
• Alias: Hypercalcemia-supravalvar aortic stenosis
• Alias: Microdeletion 7q11.23, monosomy 7q11.23
• Alias: WBS, Williams-Beuren syndrome
• Alias: Williams syndrome
• Allelic: Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic (KRAS, NRAS)
• Cardiofaciocutaneous syndrome (BRAF)
• Cardiofaciocutaneous syndrome 2 (KRAS)
• Cardiofaciocutaneous syndrome 3 (MAP2K1)
• Cutis laxa, AD (ELN)
• Kabuki syndrome 1 (KMT2D)
• Kabuki syndrome 2 (KDM6A)
• LEOPARD syndrome 1 (PTPN11)
• LEOPARD syndrome 2 (RAF1)
• LEOPARD syndrome 3 (BRAF)
• Noonan syndrome 1 (PTPN11)
• Noonan syndrome 3 (KRAS)
• Noonan syndrome 4 (SOS1)
• Noonan syndrome 5 (RAF1)
• Noonan syndrome 6 (NRAS)
• Noonan syndrome 7 (BRAF)
• Noonan syndrome 8 (RIT1)
• Smith-Magenis syndrome (RAI1)
• Supravalvar aortic stenosis (ELN)