Congenital adrenal hyperplasia (CAH) and Williams Syndrome (WS; MIM # 194050) are distinct genetic conditions characterized by unique clinical features. 21-Hydroxylase deficiency (21-OHD; MIM #201910), the most common form of CAH, arises from mutations in the CYP21A2 gene, resulting in virilization of the external genitalia in affected females, early puberty in males, and short stature. Williams syndrome, caused by a microdeletion of 7q11.23, presents with distinctive facial features, intellectual disability, unique personality traits, early puberty, and short stature. This case report describe the clinical features of a 4-year-old girl referred due to progressive virilization and developmental delay. Genetic analysis confirmed concurrent CAH and WS, identifying a novel mutation in the CYP21A2 gene (c.1442T>C). Following corticosteroid therapy initiation, the patient developed central precocious puberty. This case report delves into the pubertal change patterns in a patient affected by overlapping genetic conditions, providing valuable insights in to the intricate clinical manifestation and management of these rare complex disorders.

Williams syndrome (WS) is characterized by a range of clinical features, including cardiovascular disease, distinctive facial traits, neurobehavioral disorders, and a condition known as transient infantile hypercalcemia. Among these, endocardial calcification represents a non-specific response to severe, etiologically diverse myocardial injuries. In this report, we document a unique case involving an infant with WS who exhibited rapidly progressive arterial stenosis and left ventricular endocardial calcification, associated with a novel heterozygous deletion. While arterial stenosis is the most frequently observed cardiovascular issue in WS, instances of endocardial calcification during infancy are exceedingly rare and have not previously been reported in the context of WS.

BACKGROUND: Williams-Beuren syndrome (WBS) is a rare genetic disorder caused by hemizygous microdeletion of contiguous genes on chromosome 7q11.23. Although the phenotype features extensive heterogeneity in severity and performance, WBS is not considered to be a predisposing factor for cancer development. Currently, hematologic cancers, mainly Burkitt lymphoma, are rarely reported in patients with WBS. Here in, we report a unique case of T-cell acute lymphoblastic leukemia in a male child with WBS.
METHODS: This retrospective study analyzed the clinical data of this case receiving chemotherapy were analyzed. This is a retrospective study.
RESULTS: The patient, who exhibited a typical WBS phenotype and presented with hemorrhagic spots. Chromosomal genome-wide chip analysis (CMA) revealed abnormalities on chromosomes 7 and 9. The fusion gene STIL-TAL1 and mutations in BCL11B, NOTCH1, and USP7 have also been found and all been associated with the occurrence of T-cell leukemia. The patient responded well to the chemotherapy.
CONCLUSIONS: To the best of our knowledge, this is the first reported case of WBS in T-cell acute lymphoblastic leukemia. We want to emphasize that the occurrence of leukemia in this patient might be related to the loss of 7q11.23 and microdeletion of 9p21.3 (including 3 TSGs), but the relationship between WBS and malignancy remains unclear. Further studies are required to clarify the relationship between WBS and malignancy.

Individuals with Williams Syndrome (WS) have a specific and atypical neuropsychological profile, where language is above what is expected for their mental age, although it shows a late onset. There exists only one longitudinal study in infants younger than 20 months old with WS about early language precursors (joint attention, referential and instrumental behaviors, pointing gesture, verbal tags). The aim of this investigation is to evaluate these precursors in a baby with WS (8 to 18 months). Seven sessions of systematic observation were performed (six at baby\'s home, one at the Early Childhood Assistance center). The Battelle Developmental Inventory was used to evaluate the baby\'s development in two occasions (12 and 18 months). The results show an atypical development, and he is 5-6 months under what is expected for his chronological age. Attention towards objects prevails over preference for faces, but this one tends to increase. The pointing gesture does not emerge at the end of the observation period and therefore follows the first words that appear. The implications for the comprehension of the early linguistic profile in WS are discussed, as well as the implications for specific intervention strategies in the context of early childhood care.

Severe aortopathy in Williams syndrome can sometimes present with an initial ascending aortic pathology, followed in short order by more distal multilevel obstruction and recurrence requiring reintervention. In this series, an early, comprehensive surgical approach using a combination of various access and perfusion strategies yielded excellent long-term results.

OBJECTIVE: Cardiovascular abnormalities are common in patients with Williams syndrome and frequently require surgical intervention necessitating analgesia and sedation in a population with a unique neuropsychiatric profile, potentially increasing the risk of adverse cardiac events during the perioperative period. Despite this risk, the overall postoperative analgosedative requirements in patients with WS in the cardiac intensive care unit have not yet been investigated. Our primary aim was to examine the analgosedative requirement in patients with WS after cardiac surgery compared to a control group. Our secondary aim was to compare the frequency of major ACE and mortality between the two groups.
METHODS: Matched case-control study.
METHODS: Pediatric CICU at a Tertiary Children\'s Hospital.
METHODS: Patients with WS and age-matched controls who underwent cardiac surgery and were admitted to the CICU after cardiac surgery between July 2014 and January 2021.
METHODS: None.
RESULTS: Postoperative outcomes and total doses of analgosedative medications were collected in the first six days after surgery for the study groups. Median age was 29.8 (12.4-70.8) months for WS and 23.5 (11.2-42.3) months for controls. Across all study intervals (48 h and first 6 postoperative days), there were no differences between groups in total doses of morphine equivalents (5.0 mg/kg vs 5.6 mg/kg, p = 0.7 and 8.2 mg/kg vs 10.0 mg/kg, p = 0.7), midazolam equivalents (1.8 mg/kg vs 1.5 mg/kg, p = 0.4 and 3.4 mg/kg vs 3.8 mg/kg, p = 0.4), or dexmedetomidine (20.5 mcg/kg vs 24.4 mcg/kg, p = 0.5 and 42.3 mcg/kg vs 39.1 mcg/kg, p = 0.3). There was no difference in frequency of major ACE or mortality.
CONCLUSIONS: Patients with WS received similar analgosedative medication doses compared with controls. There was no significant difference in the frequency of major ACE (including cardiac arrest, extracorporeal membrane oxygenation, and surgical re-intervention) or mortality between the two groups, though these findings must be interpreted with caution. Further investigation is necessary to elucidate the adequacy of pain/sedation control, factors that might affect analgosedative needs in this unique population, and the impact on clinical outcomes.

Williams syndrome is an autosomal dominant multisystem disorder caused by a 1.5-1.8 Mb deletion on chromosome 7q11.23. It is characterized by facial deformations, cardiovascular abnormalities, developmental delays, gastrointestinal manifestations, and endocrine disorders.
A 1-year-old child presenting with developmental delays, special facial features, gastrointestinal bleeding, renal calcium deposition, and hypotonia was admitted to the hospital for \"hypercalcemia and gastrointestinal bleeding.\" Genetic testing showed a deletion mutation in the 7q11.23 region. Currently, the child receiving treatment to promote calcium excretion and rehabilitation training, but hypercalcemia has recurred.
The clinical phenotype of Williams syndrome is complex, and different severities, characterized by developmental delays, facial deformities, cardiovascular abnormalities, gastrointestinal symptoms and endocrine disorders, should be considered in children. The syndrome may require thorough genetic testing for diagnosis and early intervention treatment to improve patient quality of life.

OBJECTIVE: Williams syndrome (WS) is a congenital developmental disorder characterized, mainly, by distinctive facial features, cardiovascular anomalies, growth delay and a typical neurobehavioral profile. The oral manifestations have not been sufficiently described and, therefore, the aim of the current study was to present the clinical, radiographic and microbiological findings of individuals with WS.
RESULTS: A series of nine WS individuals (seven females) with mean age 21 years-old were evaluated. A complete intraoral clinical examination, a radiographic analysis using panoramic and cephalometric x-ray and a supra- and sub-gingival microbiological profiling were performed. We observed abnormal tooth morphology, excessive interdental spacing, congenitally missing permanent teeth and malocclusion. High levels of DMFT were observed and gingivitis was present in all subjects. Bacteria related to periodontal disease were detected in dental plaque. Three patients were classified with a gingival phenotype type I according to the Maynard and Wilson classification. The sella turcica bridging was a novel finding for this group of patients.
CONCLUSIONS: Due to the elevated prevalence of gingivitis, caries and malocclusion, a multidisciplinary approach including dental follow-ups should be the standard of care in WS patients.

A meta-analysis on seven large case series (>1000 cases) of chromosome microarray analysis (CMA) on products of conceptions (POC) evaluated the diagnostic yields of genomic disorders and syndromic pathogenic copy number variants (pCNVs) from a collection of 35,130 POC cases. CMA detected chromosomal abnormalities and pCNVs in approximately 50% and 2.5% of cases, respectively. The genomic disorders and syndromic pCNVs accounted for 31% of the detected pCNVs, and their incidences in POC ranged from 1/750 to 1/12,000. The newborn incidences of these genomic disorders and syndromic pCNVs were estimated in a range of 1/4000 to 1/50,000 live births from population genetic studies and diagnostic yields of a large case series of 32,587 pediatric patients. The risk of spontaneous abortion (SAB) for DiGeorge syndrome (DGS), Wolf-Hirschhorn syndrome (WHS), and William-Beuren syndrome (WBS) was 42%, 33%, and 21%, respectively. The estimated overall risk of SAB for major genomic disorders and syndromic pCNVs was approximately 38%, which was significantly lower than the 94% overall risk of SAB for chromosomal abnormalities. Further classification on levels of risk of SAB to high (>75%), intermediate (51%-75%), and low (26%-50%) for known chromosomal abnormalities, genomic disorders, and syndromic pCNVs could provide evidence-based interpretation in prenatal diagnosis and genetic counseling.

BACKGROUND: Williams syndrome (WS-OMIM 194050, orphaned number: Orpha 904) is a rare condition mostly associated with intellectual disability. People with Williams syndrome are 8 times more likely to have anxiety disorders than the general population. Therapeutic solutions to treat the anxiety remain limited, particularly nonpharmacological therapy. However, cognitive behavioral therapy (CBT) has been found efficacious in managing anxiety disorders and can be used for people with intellectual disability.
OBJECTIVE: This paper describes a protocol to assess the efficiency of a CBT program based on digital support for people with Williams syndrome and anxiety based on a research methodology designed for rare diseases.
METHODS: We will recruit 5 individuals with Williams syndrome and anxiety. They will participate in 9 CBT sessions. Participants will perform daily self-assessments of anxiety using a digital app, which will allow for ecological and repeated evaluation of their anxiety. This digital app will provide support for each therapy session. Anxiety and quality of life will be externally assessed before and after the program and at a 3-month follow-up. This is a single-case intervention research design with multiple baselines implying repeated measures of judgment criteria. The present protocol ensures high internal validity and will help identify encouraging contributions for later clinical trials.
RESULTS: Participant recruitment and data collection began in September 2019, and we project that the study findings will be available for dissemination by spring 2023.
CONCLUSIONS: This study will allow the assessment of the efficiency of a CBT program based on digital support to treat anxiety in people with Williams syndrome. Finally, the program could be used as an example of nonpharmacological therapy for rare diseases.
BACKGROUND: ClinicalTrials.gov ID: NCT03827525; https://clinicaltrials.gov/ct2/show/NCT03827525.
UNASSIGNED: DERR1-10.2196/44393.