OBJECTIVE: To explore the genetic basis for a child with supravalvular aortic stenosis. METHODS: The child and his parents were subjected to conventional G-banding karyotyping, array comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) analysis. RESULTS: No karyotypic abnormality was detected in the child and his parents. aCGH has identified a de novo 278 kb deletion encompassing the ELN gene in 7q11.23, which overlapped with the critical region of Williams-Beuren syndrome (WBS). MLPA has confirmed above findings. CONCLUSION The proband was diagnosed with atypical WBS. Deletion of the ELN gene may predispose to supravalvular aortic stenosis in the proband.
Aortic Stenosis, Supravalvular ; genetics ; Child ; Chromosome Banding ; Chromosomes, Human, Pair 7 ; genetics ; Comparative Genomic Hybridization ; Gene Deletion ; Genetic Testing ; Humans ; Williams Syndrome ; complications ; genetics

Primary hypothyroidism related to morphological and volumetric abnormalities of the thyroid gland is one of the commonest of several endocrine dysfunctions in Williams-Beuren syndrome (WBS). We report a 10-month-old boy with WBS who presented with central hypothyroidism. During the neonatal period, he had prolonged jaundice, feeding difficulties and episodes of colic that continued during early infancy. Additionally, there was slowing of growth and mild developmental delay. He underwent surgical repair for supravalvular aortic stenosis at 6 months of age. An evaluation done to exclude cortisol deficiency before initiating levothyroxine lead to the detection of secondary adrenal insufficiency, unreported previously in WBS. In addition, insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 levels were low. This report of hypopituitarism in WBS indicates a need for complete evaluation of pituitary dysfunction in children with WBS.
Adrenal Insufficiency* ; Aortic Stenosis, Supravalvular ; Child ; Colic ; Humans ; Hydrocortisone ; Hypopituitarism ; Hypothyroidism* ; Infant ; Jaundice ; Male* ; Thyroid Gland ; Thyroxine ; Williams Syndrome*

PURPOSE: Williams-Beuren syndrome (WBS) is caused by a hemizygous microdeletion of chromosome 7q11.23 and is characterized by global cognitive impairment, dysmorphic facial features, and supravalvular aortic stenosis. Endocrine dysfunctions have been reported in patients with WBS. This study was performed to investigate the frequency, clinical features, and outcomes of endocrine dysfunctions in children with WBS. METHODS: One hundred two patients were included. The diagnosis was confirmed by chromosome analysis and fluorescent in situ hybridization. Medical charts were reviewed retrospectively to analyze endocrine dysfunctions such as short stature, precocious puberty, thyroid dysfunctions, and hypocalcemia. RESULTS: The age at diagnosis was 3.7±4.4 years (one month to 19 years). Height- and weight-standard deviation score (SDS) were -1.1±1.1 and -1.4±1.4 at presentation, respectively. Short stature was found in 26 patients (28.3%) among those older than 2 years. Body mass index-SDS increased as the patients grew older (P<0.001). Two males and one female (2.9%) were diagnosed with central precocious puberty. Nine patients (8.8%) were diagnosed with primary hypothyroidism at age 4.0±4.3 years (one month to 12.1 years); their serum thyroid stimulating hormone and free T4 levels were 15.2±5.4 µU/mL and 1.2±0.2 ng/dL, respectively. Hypercalcemia was observed in 12 out of 55 patients under age 3 (22%) at the age of 14.3±6.6 months (7 to 28 months) with a mean serum calcium level of 13.1±2.1 mg/dL. CONCLUSION: Endocrine dysfunctions are not uncommon causes of morbidity in patients with WBS. The severity and outcomes of their endocrine manifestations were heterogeneous. Long-term follow-up is needed to predict the prognosis of endocrine features.
Aortic Stenosis, Supravalvular ; Calcium ; Child* ; Diagnosis ; Female ; Follow-Up Studies ; Humans ; Hypercalcemia ; Hypocalcemia ; Hypothyroidism ; In Situ Hybridization, Fluorescence ; Male ; Prognosis ; Puberty, Precocious ; Retrospective Studies ; Thyroid Gland ; Thyrotropin ; Williams Syndrome*

Williams syndrome (WS) is a developmental disorder characterized by vascular abnormalities such as thickening of the vascular media layer in medium- and large-sized arteries. Supravalvular aortic stenosis (SVAS) and peripheral pulmonary artery stenosis (PPAS) are common vascular abnormalities in WS. The natural course of SVAS and PPAS is variable, and the timing of surgery or intervention is determined according to the progression of vascular stenosis. In our patient, SVAS and PPAS showed rapid concurrent progression within two weeks after birth. We report the early manifestation of SVAS and PPAS in the neonatal period and describe the surgical treatment for stenosis relief.
Aorta ; Aortic Stenosis, Supravalvular ; Arteries ; Constriction, Pathologic* ; Heart Defects, Congenital ; Humans ; Parturition ; Pulmonary Artery* ; Tunica Media ; Williams Syndrome*

Objective. To study the clinical spectrum of Filipino patients with Williams Syndrome and to confirm the gene deletion by FISH analysis. Methods. From June 2005 to September 2008, patients who were seen at the Genetics clinic of the UP-PGH and who met the clinical criteria for Williams Syndrome were analyzed for the 7q11.23 deletion through karyotyping and FISH studies. A detailed history and a thorough dysmorphologic examination were performed. Relevant investigations included two-dimensional echocardiography, renal ultrasonography, ophthalmologic examination, developmental assessment and serum calcium determination. Result. Eight patients were included in the study. The mean age at first diagnosis was 8.5 years. All cases were sporadic. The chromosomal analysis was normal for all patients and in the FISH analysis, a 7q11.23 deletion was detected in 100% of cases. Distinctive facial features, cardiac abnormalities and developmental delay were present in all patients. The typical behavior of overfriendliness was observed in the majority of cases. Hypercalcemia was documented in only one case and no renal anomalies were detected. Conclusion. The craniofacial features were similar among patients but there is a broad spectrum of severity of clinical features in cardiovascular abnormalities, personality, behavior traits and mental capacity.
CYTOGENETICS ; GENETICS ; WILLIAMS SYNDROME ; NERVOUS SYSTEM DISEASES ; NEUROLOGIC MANIFESTATIONS ; NEUROBEHAVIORAL MANIFESTATIONS ; INTELLECTUAL DISABILITY ; GENE DELETION ; IN SITU HYBRIDIZATION, FLUORESCENCE ; AORTIC STENOSIS, SUPRAVALVULAR ; DIAGNOSIS ; DIAGNOSTIC TECHNIQUES AND PROCEDURES ; CLINICAL LABORATORY TECHNIQUES ; CYTOLOGICAL TECHNIQUES ; HISTOCYTOLOGICAL PREPARATION TECHNIQUES ; STAINING AND LABELING ; IN SITU HYBRIDIZATION ; ;

BACKGROUND: Surgery for mitral valve disease in children carries both technical and clinical difficulties that are due to both the wide spectrum of morphologic abnormalities and the high incidence of associated cardiac anomalies. The purpose of this study is to assess the outcome of mitral valve surgery for treating congenital mitral regurgitation in children. MATERIAL AND METHOD: From 1997 to 2007, 22 children (mean age: 5.4 years) who had congenital mitral regurgitation underwent mitral valve repair. The median age of the patients was 5.4 years old and four patients (18%) were under 12 months of age. 15 patients (68%) had cardiac anomalies. There were 13 cases of ventricular septal defect, 1 case of atrial septal defect and 1 case of supravalvar aortic stenosis. The grade of the preoperative mitral valve regurgitation was II in 4 patients, III in 15 patients and IV in 3. The regurgitation was due to leaflet prolapse in 12 patients, annular dilatation in 4 patients and restrictive leaflet motion in 5 patients. The preoperative MV Z-value and the regurgitation grade were compared with those obtained at follow-up. RESULT: MV repair was possible in all the patients. 19 patients required reduction annuloplasty and 18 patients required valvuloplasty that included shortening of the chordae, papillary muscle splitting, artificial chordae insertion and cleft closure. There were no early or late deaths. The mitral valve regurgitation after surgery was improved in all patients (absent=10, grade I=5, II=5, III=2). MV repair resulted in reduction of the mitral valve Z-value (2.2+/-.1 vs. 0.7+/-.3, respectively, p<0.01). During the mid-term follow-up period of 3.68 years, reoperation was done in three patients (one with repair and two with replacement) and three patients showed mild progression of their mitral regurgitation. CONCLUSION: Our experience indicates that mitral valve repair in children with congenital mitral valve regurgitation is an effective and reliable surgical method with a low reoperation rate. A good postoperative outcome can be obtained by preoperatively recognizing the intrinsic mitral valve pathophysiology detected on echocardiography and with the well-designed, aggressive application of the various reconstruction techniques.
Aortic Stenosis, Supravalvular ; Child ; Dilatation ; Echocardiography ; Follow-Up Studies ; Heart Septal Defects, Atrial ; Heart Septal Defects, Ventricular ; Humans ; Incidence ; Mitral Valve ; Mitral Valve Insufficiency ; Papillary Muscles ; Prolapse ; Reoperation

Adult ; Aortic Stenosis, Supravalvular ; Child ; Female ; Humans ; Mothers

OBJECTIVETo evaluate the cardiovascular manifestations of Williams syndrome (WS) confirmed by fluorescence in situ hybridization (FISH).

METHODSBetween July 2004 and January 2007, FISH was used to confirm diagnosis in 71 suspected WS cases by detecting chromosome 7q microdeletion. Cardiovascular abnormalities were assessed by echocardiography and Doppler echocardiography.

RESULTSForty out of 71 patients were detected to have Elastin gene locus microdeletion, 25 patients (25/40, 62.5%) had at least one cardiac anomaly; among these patients, supravalvular aortic stenosis (SVAS) was diagnosed in 18 patients (18/25, 72%) and 6 of them had complex abnormalities. Patent ductus arteriosus was diagnosed in 3 patients (3/25, 12%, 1 was associated with other malformations), isolated pulmonary stenosis in 1 patient (1/25, 4%), isolated coarctation of aorta in 2 patients (2/25, 8%), and hypertension in 2 patients (2/25, 8%), mild aortic regurgitation in 2 patients, mild mitral regurgitation and moderate mitral regurgitation in 3 patients respectively.

CONCLUSIONA detailed cardiac evaluation should be performed in all patients with Williams syndrome due to the high frequency of cardiovascular abnormalities.

Adolescent ; Adult ; Aortic Stenosis, Supravalvular ; complications ; diagnosis ; Cardiovascular Abnormalities ; complications ; diagnosis ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Williams Syndrome ; complications ; diagnosis ; Young Adult

Williams syndrome is a rare genetic disorder with a frequency of one per 20,000-50,000 live births. It is caused by a deletion of one elastin allele located within chromosome subunit 7q11.23 (long arm). This syndrome is frequently accompanied by congenital heart disease, facial anomalies, and mental retardation and as a result, anesthetic management may be complicated by hemodynamic instability and difficult intubation. Also, as it was reported that this disease is associated with malignant hyperthermia, careful anesthetic selection is required. We experienced the anesthetic management of a 3-year-old girl with Williams syndrome who received dental treatment for severe dental caries under general anesthesia, and of a 4-year-old girl underwent aortoplasty for supravalvular aortic stenosis. Airway management and tracheal intubation was accomplished successfully in both patients. For anesthetic management, propofol, fentanyl and rocuronium, and fentanyl, isoflurane and vecuronium were used in the first and second patients, respectively. Surgeries were performed uneventfully in both cases, and the patients were discharged without complication.
Airway Management ; Alleles ; Anesthesia ; Anesthesia, General ; Aortic Stenosis, Supravalvular ; Child, Preschool ; Dental Caries ; Elastin ; Female ; Fentanyl ; Heart Defects, Congenital ; Hemodynamics ; Humans ; Intellectual Disability ; Intubation ; Isoflurane ; Live Birth ; Malignant Hyperthermia ; Propofol ; Vecuronium Bromide ; Williams Syndrome*

OBJECTIVETo introduce the experience of diagnosis and surgical treatment of Williams syndrome combined with cardiovascular disease.

METHODSBetween October 1996 and June 2003, 8 patients of Williams syndrome with cardiovascular disease were admitted in Fuwai hospital. Seven patients underwent surgical correction. One didn't undergo surgical procedure. There were 6 male and 2 female ranging from 1.5 to 12.0 years old (medium age 6.4). Three had localized type supravalvular aortic stenosis and 5 diffused type supravalvular aortic stenosis. In them, 2 patients were combined with peripheral pulmonary stenosis. Single patch aortoplasty were performed in 6 cases, and inverted bifurcated patch aortoplasty in one patient.

RESULTSOne patient died and one patient suffered renal insufficiency. In the early postoperative period, the mean speed of flow was reduced to 1.7 m/s from 4.6 m/s, and the mean systolic pressure gradient was reduced from 91 mm Hg to 18 mm Hg. Six patients were followed up 16 to 91 months. There were 5 cases in NYHA function class I, and one in class II.

CONCLUSIONSatisfied result can be achieved in surgical treatment of Williams syndrome with supravalvular aortic stenosis, but it is not in combined with peripheral pulmonary stenosis.

Aortic Stenosis, Supravalvular ; complications ; congenital ; surgery ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Pulmonary Valve Stenosis ; complications ; congenital ; surgery ; Treatment Outcome ; Williams Syndrome ; complications ; surgery