Williams Syndrome Presenting with Recurrent and Persistent Vomiting: A Case Report

1. INTRODUCTION

Williams-Beuren syndrome (WS) is a rare multisystem genetic disorder resulting from a heterozygous microdeletion at chromosome 7q11.23, with reported prevalence estimates ranging from 1 in 7,500 to 1 in 20,000 live births [1-3]. The clinical phenotype is highly variable but classically includes distinctive elfin-like facial features, supravalvular aortic stenosis or other cardiovascular anomalies, mild to moderate intellectual disability, a characteristic behavioral phenotype (often hypersociability and relative strengths in language and music), and failure to thrive during infancy [3-5]. Idiopathic infantile hypercalcemia is documented in up to half of affected infants and is frequently implicated in gastrointestinal disturbances, including vomiting, constipation, anorexia, and feeding difficulties [6, 7]. Although gastrointestinal symptoms are well recognized in WS, recurrent, cyclic, or treatment-refractory vomiting as the predominant or initial manifestation is uncommon and can substantially delay recognition of the underlying genetic diagnosis [8, 9]. We describe an 11-month-old male infant who presented with severe, persistent vomiting and dehydration that had prompted three hospital admissions over the preceding two months, with rapid recurrence after each discharge despite conventional antiemetic and rehydration measures. Physical examination revealed the typical dysmorphic facial features of WS and a grade 3/6 systolic murmur. Laboratory evaluation confirmed severe hypercalcemia, and echocardiography demonstrated supravalvular aortic stenosis with the characteristic hourglass appearance.

Standard therapy for hypercalcemia (intravenous hydration, loop diuretics, and corticosteroids) was largely ineffective, but serum calcium levels normalized rapidly and remained stable after initiation of cinacalcet. The clinical diagnosis of Williams-Beuren syndrome was made on the basis of the characteristic phenotype and cardiovascular findings. Reporting this case is justified for several reasons. First, severe hypercalcemia presenting primarily as cyclic, refractory vomiting is an atypical and diagnostically challenging initial manifestation of WS, often leading to prolonged gastrointestinal investigations and repeated hospitalizations-particularly in settings where prompt genetic testing is not readily available. Second, the literature on management of infantile hypercalcemia in WS is limited, and published experience with cinacalcet in this specific context remains scarce. Third, by documenting the diagnostic pathway, biochemical course, and therapeutic response to cinacalcet, this report provides useful clinical detail, supports earlier consideration of WS in similar presentations, and contributes to the small body of evidence that may help inform treatment decisions in future pediatric cases with comparable features.

2. CASE PRESENTATION

An 11-month-old male infant was admitted to the emergency department with persistent vomiting and signs of dehydration. Over the previous two months, he had required three separate hospitalizations for identical symptoms. Each episode responded temporarily to intravenous fluids and supportive care, but vomiting recurred within days of discharge. This report has two primary objectives: first, to describe an uncommon initial presentation of Williams-Beuren syndrome in infancy-namely, recurrent and refractory vomiting attributable to severe hypercalcemia-and second, to document a therapeutic experience in which conventional measures (hydration, diuretics, and corticosteroids) failed to control the hypercalcemia, whereas cinacalcet resulted in rapid and sustained normalization of serum calcium.

3. DISCUSSION

Williams-Beuren syndrome (WS) is a multisystem genetic disorder with a highly variable phenotype. Core clinical features include distinctive elfin-like facial dysmorphism, congenital cardiovascular anomalies (most commonly supravalvular aortic stenosis), mild to moderate intellectual disability, a characteristic hypersociable behavioral profile, and failure to thrive in infancy [10, 11]. The diagnosis is usually established by demonstrating the characteristic microdeletion at 7q11.23 using fluorescence in situ hybridization (FISH) or chromosomal microarray analysis [10, 12]. Hypercalcemia occurs in 5–50% of infants with WS and frequently manifests with nonspecific symptoms such as irritability, vomiting, constipation, polyuria, dehydration, and poor feeding [1, 13, 14]. The underlying mechanisms remain incompletely understood but are thought to involve increased sensitivity to vitamin D, dysregulation of calcium homeostasis, and impaired renal calcium handling [15, 16]. In the majority of cases, hypercalcemia is transient and responds to conservative measures; however, severe or persistent hypercalcemia may necessitate pharmacologic therapy [6, 7].

Although gastrointestinal symptoms are relatively common in WS, recurrent, cyclic, or treatment-refractory vomiting as the predominant initial presentation is uncommon and can significantly delay recognition of the syndrome [17]. Such cases often prompt extensive gastrointestinal investigations (endoscopy, imaging, motility studies), repeated hospitalizations, and prolonged diagnostic uncertainty, particularly in resource-limited settings where genetic testing is not immediately accessible. The coexistence of dysmorphic facial features and congenital heart disease should prompt clinicians to consider a syndromic etiology rather than pursuing isolated gastrointestinal pathology [17, 18]. Standard initial management of hypercalcemia includes aggressive intravenous hydration, loop diuretics (furosemide), dietary calcium restriction, and, in some cases, short-term glucocorticoids or bisphosphonates [6, 19]. In refractory cases, cinacalcet-a calcimimetic agent that acts as an allosteric agonist of the calcium-sensing receptor-has been reported to effectively reduce serum calcium levels in patients with WS [20, 21]. In the present case, conventional measures were insufficient, but cinacalcet administration resulted in rapid normalization of serum calcium and complete resolution of vomiting, with sustained biochemical and clinical stability over three months of follow-up. Williams-Beuren syndrome is associated with considerable long-term morbidity arising from cardiovascular complications, neurodevelopmental impairment, endocrine disturbances (including hypercalcemia and hypogonadism), and other organ system involvement. Early recognition, multidisciplinary care (involving cardiology, endocrinology, developmental pediatrics, and genetics), and tailored interventions are essential to optimize outcomes and prevent avoidable complications [10, 22].

4. LIMITATIONS

A principal limitation of this case report is the absence of molecular confirmation of the 7q11.23 microdeletion. Fluorescence in situ hybridization (FISH) and chromosomal microarray analysis were not available locally, and referral for genetic testing was not pursued during the acute admission due to resource constraints. The diagnosis of Williams-Beuren syndrome was therefore established on clinical and echocardiographic criteria alone, relying on the presence of the characteristic facial phenotype and supravalvular aortic stenosis. This clinical diagnostic strategy is consistent with established diagnostic guidelines for WS in resource-limited settings and has been applied in several previously published cases where molecular testing was not immediately feasible. Nevertheless, the lack of genetic verification means that other phenotypically overlapping conditions cannot be completely excluded, and the ability to offer precise recurrence risk counseling or detailed genotype-phenotype correlation is restricted. In future cases, molecular confirmation is strongly recommended whenever diagnostic facilities permit, as it provides greater diagnostic certainty and supports more accurate prognostic assessment.

CONCLUSION

This case draws attention to an unusual presentation of Williams–Beuren syndrome (WS), in which recurrent vomiting was the main clinical problem and only later was shown to be related to marked hypercalcemia. Gastrointestinal symptoms are known to occur in WS, but vomiting as an isolated and dominant feature, without early cardiac or developmental abnormalities, is uncommon and can easily delay diagnosis. As a result, many infants undergo repeated hospital admissions and extensive gastrointestinal testing before a syndromic cause is suspected. When distinctive facial features are accompanied by a systolic murmur suggestive of supravalvular aortic stenosis and hypercalcemia that does not respond to routine treatment, WS should be considered even if genetic testing is not immediately available. This point is especially relevant in regions with limited access to molecular diagnostics. Our experience also adds to the small number of reports describing the use of cinacalcet in WS-related hypercalcemia. In this patient, standard measures-such as intravenous fluids, loop diuretics, dietary calcium restriction, and short-term corticosteroid therapy-did not achieve adequate biochemical control. After cinacalcet was introduced, serum calcium levels normalized quickly, vomiting resolved, and the child remained clinically stable during three months of follow-up. This response supports previous observations that cinacalcet may be a useful and well-tolerated option when first-line therapies are ineffective in children with WS. Early identification of WS is therefore important. A timely diagnosis makes it possible to treat acute metabolic disturbances promptly and to arrange appropriate long-term follow-up for cardiac, endocrine, developmental, and nutritional issues. Physicians in pediatrics, gastroenterology, endocrinology, and emergency care should keep WS in mind when an infant presents with otherwise unexplained recurrent vomiting together with hypercalcemia. Earlier recognition can reduce unnecessary investigations, prevent complications, and ultimately improve outcomes in this multisystem genetic condition.

CLINICAL IMPLICATIONS

This case reminds clinicians that persistent vomiting together with high serum calcium in infancy should not be dismissed, even when early laboratory and gastrointestinal studies appear unrevealing. Although Williams–Beuren syndrome (WS) is rare, it deserves consideration when vomiting is recurrent or difficult to manage, particularly if there are subtle facial differences or mild cardiac findings in the background. Keeping WS in mind at this stage can shorten the diagnostic process and spare the child from unnecessary or invasive investigations. The favorable outcome seen after starting cinacalcet is also clinically meaningful. In children whose hypercalcemia does not improve with fluids, dietary measures, or other standard treatments, cinacalcet may provide effective biochemical control and symptom relief. Its use in this setting has the potential to reduce hospital admissions and improve daily functioning for affected infants and their families. Since WS involves multiple organ systems, ongoing follow-up with cardiology, endocrinology, and developmental services remains an important part of care.

WHAT THIS CASE ADDS

This case describes an unusual early presentation of Williams–Beuren syndrome in which severe hypercalcemia led to recurrent, treatment-resistant vomiting and repeated hospital admissions for gastrointestinal evaluation. It also reports the effective use of cinacalcet in an infant after standard measures, including hydration, diuretics, and dietary calcium restriction, failed to control serum calcium levels, thereby contributing to the limited pediatric data on this therapy. In addition, the case highlights the practical importance of recognizing characteristic facial features and basic echocardiographic findings in supporting the diagnosis, particularly in settings where rapid genetic testing is not readily available.

FUTURE PERSPECTIVES

Metabolic and gastrointestinal signs often appear early in WS, offering a chance for earlier detection. Clinicians would benefit from strategies that bring together lab tests, physical traits, and heart evaluations to identify patients promptly. Making rapid genetic tests, like microarray or FISH, more accessible-especially in under-resourced areas-could help confirm diagnoses sooner and allow treatment to start earlier. At the same time, long-term studies are needed to better understand how cinacalcet affects infants and young children with syndromic hypercalcemia, including both safety and effectiveness. Clear, practical treatment guidelines, including dosing and follow-up recommendations, could further improve care. Finally, educating general pediatricians and emergency physicians about the subtler presentations of syndromes like WS is essential for timely recognition and effective management in daily practice.

REFERENCES