American Journal of Medical Genetics 118A:372–376 (2003) Clinical Report Portal Hypertension in Williams Syndrome: Report of Two Patients Miguel Del Campo Casanelles, 1 * Juan Jose ´ Gil-Ferna ´ ndez, 2 Luis F. Magano Casero, 1 Manuel Garcı ´a Bengoechea, 3 Rosario Serrano, 4 Jose ´ Marı ´a Ferna ´ ndez Ran ˜ ada, 2 and Luis Alberto Pe ´ rez Jurado 1 1 Genetics Unit, Department of Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain 2 Department of Hematology, Clı´nica Ruber, Madrid, Spain 3 Division of Gastroenterology, Hospital Ara ´ nzazu, Donostia, Spain 4 Department of Pathology, Clı´nica Ruber, Madrid, Spain Williams or Williams-Beuren syndrome (WBS) is a developmental disorder with multisystemic manifestations characterized by distinctive facial features, mental disabi- lity with unique cognitive and personality profiles, vascular stenoses, growth retarda- tion, and occasional infantile hypercalce- mia, caused by haploinsufficiency for genes deleted in chromosome band 7q11.23. How- ever, with the exception of arterial stenoses caused by haploinsufficiency for the elastin gene (ELN), no specific implication of any other gene in the phenotype has been estab- lished. We present two patients with portal hypertension leading to splenomegaly and pancytopenia carrying the common 1.5 Mb WBS deletion. We propose this is an addi- tional severe vascular complication of ELN deficiency and discuss the specific charac- teristics of the portal venous tract that could explain the impact of ELN deficiency in that venous territory. This complication is poten- tially lethal and should thus be considered in any patient with WBS and splenomegaly. ß 2003 Wiley-Liss, Inc. KEY WORDS: Williams syndrome; portal hypertension; splenomegaly; pancytopenia; elastin INTRODUCTION Williams or Williams-Beuren syndrome (WBS) is a developmental disorder with multisystemic mani- festations characterized by distinctive facial features, mental disability with unique cognitive and personality profiles, vascular stenoses, growth retardation, and oc- casional infantile hypercalcemia, caused by haploinsuf- ficiency for genes deleted in chromosome band 7q11.23. The great majority of patients show very similar (1.5 Mb) heterozygous deletions that arise as a consequence of unequal crossing-over between highly homologous regional segmental duplications, and in- clude at least 25 identified genes [Peoples et al., 2000; DeSilva et al., 2002; Merla et al., 2002]. While haplo- insufficiency for the elastin gene (ELN) is known to be the cause of the vascular stenoses, the other features of WBS have not been clearly attributed to specific genes. Cardiovascular manifestations are detected in about 75% of confirmed patients during their lifetime [Pe ´rez Jurado, 2001]. Supravalvular aortic stenosis (SVAS) is most common, peripheral pulmonic stenosis being next in frequency. However, involvement of other muscular arteries may occur, and vascular narrowing may be progressive. We report two patients with WBS who developed massive splenomegaly and severe pancytopenia secon- dary to portal hypertension. We propose that portal hypertension may be an unusual complication in WBS related to the generalized dysplasia of the vascular wall caused by elastin haploinsufficiency. CLINICAL REPORTS Patient 1 This 28-year-old male was the first of two children. Family history was unremarkable. Pregnancy and delivery at 42 weeks were uneventful. Following detec- tion of a heart murmur, an echocardiogram and cardiac catheterization showed mild SVAS and pulmonic *Correspondence to: Dr. Miguel Del Campo Casanelles, M.D., Ph.D., Genetics Unit, Department of Experimental Sciences, Universitat Pompeu Fabra, Dr. Aiguader 80, 08003 Barcelona, Spain. E-mail: miguel.delcampo@cexs.upf.es Received 10 July 2002; Accepted 30 September 2002 DOI 10.1002/ajmg.a.10205 ß 2003 Wiley-Liss, Inc.