Thyroid hemiagenesis and elevated thyrotropin levels in a child with Williams syndrome.

A girl with Williams syndrome (WS) presented with elevated thyrotropin (TSH) levels (7.0 microU/ml), normal free thyroid hormone concentrations, and absent antithyroid autoantibodies. Thyroid ultrasonography and scintigraphy showed hemiagenesis of the left lobe and no evidence of ectopic tissue. TSH response to thyrotropin-releasing hormone (TRH) injection (200 microg/mq, i.v.) was exaggerated and prolonged, suggesting subclinical hypothyroidism. The biological activity of circulating TSH was slightly below the normal range [TSH bioactivity (B) to immunoreactivity (I) ratio (TSH B/I) = 0.4, normal: 0.6-2.2]. These abnormalities are similar to those seen in patients with hypothalamic hypothyroidism. Thyroid function is not a recognized manifestation of WS and is not routinely investigated. However, abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis and thyroid dysgenesis have been found in other WS cases. Genes mapping at 7q11.23, contiguous to the chromosomal region deleted in most WS patients, may be involved in the development of the thyroid gland, contributing to the complex phenotype of WS.     

Cerebrovascular stenoses with cerebral infarction in a child with Williams syndrome

We report on a patient with Williams syndrome who suffered a cerebrovascular accident. Clinical evaluation demonstrated the presence of carotid and cerebral arterial stenoses. We believe these lesions led to acute cerebrovascular ischemia and a non-hemorrhagic cerebral infarction. It is possible the stenoses were exacerbated by a vasculitis. The stenoses were identified by both invasive and noninvasive imaging studies. These studies may have a role in the evaluation of persons with Williams syndrome. © 1994 Wiley-Liss, Inc.     

Low MSAFP levels and Williams syndrome

Williams syndrome (WS) is associated with a deletion of the elastin gene in over 90% of cases. We report maternal serum alpha feto-protein (MSAFP) levels in 5 women whose fetuses were later diagnosed as having WS. MSAFP levels ranged from 0.5–0.8 multiples of the median (MOM). Although further confirmation is necessary, it appears that MSAFP levels are lower than the median in WS. This apparent association has implications for counselling women following maternal serum screening. Am. J. Med. Genet. 72:448–450, 1997. © 1997 Wiley-Liss, Inc.     

Coeliac disease in Williams syndrome

BACKGROUND—Coeliac disease (CD) has been reported in several patients affected by chromosomal disorders, including Down syndrome (DS) and Turner syndrome (TS). CD has also been found in sporadic Williams syndrome (WS) patients. In this study, CD was evaluated in a consecutive series of patients with WS, in order to estimate if the prevalence of CD in WS patients is higher than in the general population.
METHODS AND RESULTS—A consecutive series of 63 Italian patients with WS was studied by analysing the dosage of antigliadin antibodies (AGA) IgA and antiendomisium antibodies (AEA). In patients with positive AGA and AEA, small bowel biopsy was performed. The prevalence of CD in our WS population was compared with that estimated in a published series of 17 201 Italian students. Seven WS patients were found to be positive for AGA IgA and AEA. Six of them underwent small bowel biopsy, which invariably disclosed villous atrophy consistent with CD. The prevalence of CD in the present series of WS patients was 9.5% (6/63), compared to 0.54% (1/184) in the Italian students (p<0.001).
CONCLUSION—The present results suggest that the prevalence of CD in WS is higher than in the general population and is comparable to that reported in DS and TS. AGA and AEA screening is recommended in patients with WS.


Keywords: Williams syndrome; coeliac disease     

Williams syndrome in adults

There are few published reports of adults with Williams syndrome (WS). We have evaluated ten adult WS patients. The patients in our study were very variable in clinical presentation, ranging from severely affected patients with complicated medical histories to mildly affected patients who are generally in good health. Cardiovascular anomalies and hypertension were frequent. Supravalvular aortic stenosis was seen in four patients, mitral valve prolapse in three, bicuspid aortic valve in one, valvular aortic stenosis in one, and pulmonary stenosis with right ventricular hypertrophy in one. Typical facial features included stellate irides, prominent cheeks, full lips, and micrognathia. Mental retardation was seen in all patients. Verbal skills were better developed than motor skills. All patients in our study lead active lives, and most are involved in sports. Some hold supervised jobs. Eight of our patients live with their parents and two in group homes. Independent living is restricted by their mental and adaptive limitations. © 1992 Wiley-Liss, Inc.     

Gait function in adults with Williams syndrome

Despite early neurological reports of gait abnormalities in Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, there has not yet been any systematic investigation of gait dysfunction in this disorder. The current study examined the gait characteristics in adults with WS and a neurologically normal control group as they walked at self-selected slow, preferred and fast speeds using the GAITRite walkway. The WS group showed hypokinetic gait, which manifested as reduced gait speed and stride length, but with a disproportionate increase in cadence (stepping frequency) as speed was increased. The WS group also showed increased variability of stride length and a broad based stepping pattern implicating a compensatory strategy for postural instability. Performance IQ correlated significantly with stride length in the WS group. While these results should be considered preliminary due to the small sample size, these findings have implications for our understanding of the neural basis of gait dysfunction in WS.     

Infantile spasms in two children with Williams syndrome

We describe two children with Williams syndrome and infantile spasms. The diagnosis of Williams syndrome was confirmed by documentation of a deletion of the elastin gene/Williams syndrome region at 7q11.23. The diagnosis of infantile spasms was confirmed through the presence of interictal hypsarrhythmia. This represents one of the first reports of infantile spasms in the Williams syndrome. Am. J. Med. Genet. 71:54–56, 1997. © 1997 Wiley-Liss, Inc.     

Figure copying in Williams syndrome and normal subjects

We evaluated the copying abilities of ten subjects with Williams syndrome (WS; age 6–14 years) and ten normally developing children (age 3–6 years) matched for mental age using the matrices component of the Kaufman Brief Intelligence Test (mKBIT). Each subject copied six figures, including line drawings of closed and open geometrical shapes (alone and in combination), crossed lines, and geometrical shapes made of distinct small, filled circles. Qualitatively, subjects of both groups made comparable copies, although several subjects with WS drew a continuous line when copying figures composed of distinct circles. Quantitatively, the goodness of the copies was assessed by three human observers who rated on an analog scale the similarity of each copy to its visual template. Ratings were converted to a scale from zero (completely different) to 100 (the same) for statistical analyses. We found the following. First, the overall goodness of copies of the templates was very similar between the WS and control groups (WS: mean=46.7, range=0.89–95.4; control: mean=54.5, range=0.89–98.2). Second, there were systematic differences in the goodness of copies between the two groups, depending on the features of the figures. Specifically, the goodness of copies of control subjects was almost the same as that of WS subjects for simple line figures, but was consistently better for composite line figures, and even better for figures in which the shape was made of small, filled circles. Third, there was a significant relation between the goodness of copies (dependent variable) and mental age (mKBIT, independent variable) in both groups, although it was stronger and more highly statistically significant in the control than the WS group. These findings indicate that the principles guiding copying are similar in the two groups and suggest that WS is a case of developmental rather than deviance disorder.An erratum to this article can be found at     

Independence and adaptive behavior in adults with Williams syndrome

This study describes the adjustment of 70 adults with Williams syndrome, in terms of self-help skills, independence, and occupational levels. Although the overall mean IQ of the group (62.00) was within the mild mental handicap range, relatively few individuals were able to attain a high level of independence or cope with the demands of employment. Adaptive behavior scores were significantly below chronological age. Outcome measures were compared with available data on other groups of adults of similar age and level of intellectual impairment. Implications for the community care of adults with Williams syndrome are discussed. Am. J. Med. Genet. 70:188–195, 1997. © 1997 Wiley-Liss, Inc.     

Williams syndrome as a model of genetically determined right-hemisphere dominance

Studies were carried out on the dermatoglyphics (skin ridge marks) on the hands of children with Williams syndrome; this is an inherited disease with cardiovascular pathology and a characteristic facial phenotype (“elf” facies), along with specific mental and cognitive disturbances. The results suggest a characteristic dermatoglyphic type with the presence of complex whorls on the fingers and a clear predominance of marks of greater complexity on the left hand; this is a very rare trait in normal people and in those with other inherited nervous system disorders. The features of the dermatoglyphic pattern serve as a characteristic marker of a genetically determined state of the human central nervous system, and suggests directions for neurophysiological studies of children with Williams syndrome as a unique model for analysis of higher nervous function in humans. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences; Medical Genetics Center, N. F. Filatov DKB, Moscow. Translated from Fiziologicheskii Zhurnal im. I. M. Sechenova, Vol. 81, No. 8, pp. 81–84, August, 1995.     

Bilateral vocal cord paralysis in Williams syndrome

Stewart FJ, Dalzell M, McReid M, Cinnamond MJ. Bilateral vocal cord paralysis in Williams syndrome.
Clin Genet 1993: 44: 164–165. © Munksgaard, 1993
Williams syndrome was first described in 1961 (Williams et al. 1961) and is a well-recognised clinical syndrome characterised by growth deficiency, learning difficulties and a typical facies. We describe a 9-year-old girl with classical features of Williams syndrome who presented with acute vocal cord paralysis for which no other cause was found.     

Central precocious puberty in a girl with Williams syndrome: the result of treatment with GnRH analogue

Williams syndrome (WS) is a well-known microdeletion syndrome characterized by specific facial features, retardation in growth and development, typical personality and cardiac defects. Poor growth potential is further affected by central precocious puberty (CPP) which is frequent in these patients. A WS patient with CPP is presented, whose pubertal development and bone age progression were arrested by administration of GnRH analogues. The case is reported to discuss the role of GnRH analogues for management of CPP in patients with WS.     

BAZ1B is a candidate gene responsible for hypothyroidism in Williams syndrome

Williams syndrome (WS) is a rare neurodevelopmental disorder associated to a hemizygous deletion of 28 genes located on chromosome 7q11.23. WS affected subjects frequently suffer from several endocrine abnormalities including hypothyroidism due to defects in thyroid morphology. To date, several genes involved in thyroid dysgenesis have been identified, nonetheless, none of them is located in the 7q11.23 region. Thus, the hypothyroidism-linked molecular features in WS are not yet known. In this study we focused on one of the WS deleted gene, BAZ1B, demonstrating that its downregulation in thyroid cells leads to cell viability and survival decrement. Taking together, our results show that BAZ1B could be the mainly responsible for thyroid defects observed in some of WS patients and that these alterations are activated by PTEN-mediated mechanisms.     

Genotype-phenotype correlation in two sets of monozygotic twins with Williams syndrome

We report on two sets of monozygotic (MZ) twins with Williams syndrome (WS), following the 6 pairs already reported in the literature. We have confirmed monozygosity of both pairs of twins by DNA microsatellite analysis and the clinical diagnosis by fluorescence in situ hybridization using a WS-specific probe. Analysis of the concordance of different clinical signs between members of each pair of twins benefitted from a lengthy clinical follow-up, from 24 months to 7 years in one pair, and from the age of 15 years with reevaluation after 2 years in the other pair. Most clinical signs were concordant in the twins of each pair, with differences present at younger ages, mainly minor facial anomalies, being attenuated with time. Developmental delay was substantially concordant, but the degree differed slightly between twins in each pair. Inguinal hernia was present in a single twin in pair 1. Facial anomalies and other signs attributable to connective tissue abnormalities were also displayed by only one twin in both sets, suggesting that the WS genotype has only a predisposing role in the development of these signs. Am. J. Med. Genet. 69:107–111, 1997. © 1997 Wiley-Liss, Inc.     

Skin elastic fibers in Williams syndrome

The elastin gene is consistently deleted in Williams syndrome and as this protein represents the major component of the elastic fibers of the dermis, we sought to investigate skin elastic fibers in Williams syndrome as a key to unraveling extracellular matrix disorganization in this condition. Both morphometric parameters analyzed by using automated image analysis and immunofluorescence labeling with monoclonal antibodies against elastin and fibrillin 1 showed a disorganized pre-elastic (oxytalan and elaunin) and mature elastic fibers in the dermis of 10 Williams syndrome patients compared with five healthy children and one patient with isolated supravalvular aortic stenosis. Skin biopsies in Williams syndrome patients provide a simple mean to elucidate extracellular matrix anomalies. Hopefully, this method could give clues to the understanding of the elastic network anomalies in this condition and even to the consequences of these latter on elasticity and resilience of other tissues such as the arterial tree. Am. J. Med. Genet. 87:134–138, 1999. © 1999 Wiley-Liss, Inc.