Investigators from Jichi and Yokohama City Universities, Japan, report a patient with the common Williams-Beuren syndrome (WBS) deletion in 7q11.23 who presented with severe cerebral and cerebellar dysplasia and progressive hypertrophic cardiomyopathy. Facial characteristics included downward slanting of the palpebral fissure, blepharophimosis, strabismus, right iris hypopigmentation, low-set ears, high-arched palate, broad nose, thick lips, wide mouth, and micrognathia. Associated abnormalities included a deep, husky voice, hearing impairment by brainstem auditory responses, hypoplastic toes with nail aplasia, and contractures of hip and knee joints. Progressive hypertrophic cardiomyopathy manifested with ventricular septal defect at birth, right ventricular hypertrophy at 1 month, and left ventricular hypertrophy and mitral valve insufficiency at age 2 months. Supravalvular aortic stenosis commonly found with WB syndrome was absent.

Brain MRI showed congenital hydrocephalus, hypoplasia of the cerebellum and brain stem, and agenesis of the corpus callosum. At 3 months of age, he developed recurrent generalized tonic convulsions daily. Laboratory findings included mild hypocalcemia, low blood sugar, and low free T4 and high TSH consistent with hypothyroidism. The patient died with heart failure at age 1 year 5 months. [1]

COMMENT. The original reports of Williams (alt. Williams-Beuren) syndrome appeared in the journal Circulation, 1961 and 1962, with emphasis on “Supravalvular aortic stenosis.” Diagnosis of Williams syndrome involves recognition of physical features and markers, followed by a confirmatory genetic test. This case report is presented as the first patient with WB syndrome to have a congenital CNS anomaly in addition to progressive hypertrophic cardiomyopathy. Neurologic symptoms previously reported include mild microcephaly, intellectual disability, and personality disorders (hyperverbal). Abnormalities in the cerebellum, right parietal cortex, and left frontal cortex are consistent with visual-spatial difficulties. Increased volume of the left auditory cortex correlates with a rhythm propensity and fondness of music. Neuropsychological, neurological, and neuroanatomical profile of Williams syndrome is compared to that of Down syndrome [2]. For a clinical guide to symptoms and diagnosis of Williams and other syndromes, see Millichap JG. Neurological Syndromes. New York: Springer; 2013. 279 p. [3]