Background: Waardenburg syndrome is a rare genetic disorder, most often inherited in an autosomal dominant pattern, affecting approximately 1 in 40,000 individuals and accounting for 2–5% of congenital hearing loss. It occurs across all ethnic groups and shows no gender predilection.Pathogenic mutations disrupt the migration and proliferation of neural crest cells, affecting melanocytes in the eyes, skin, hair, and the stria vascularis of the cochlea. Key clinical features include congenital sensorineural hearing loss, heterochromic or hypoplastic blue irides, white forelock or early graying of scalp hair (<30 years), and a suggestive family history. Diagnosis is primarily clinical, supported by audiological evaluation and, when possible, molecular genetic testing.There is no curative treatment; early supportive interventions, particularly hearing rehabilitation, are essential. With timely management, most patients maintain normal life expectancy and developmental potential. Given the syndrome’s rarity and the distinctive clinical features, we present this case to highlight key diagnostic signs and facilitate recognition in other patients.Case presentation Summary: A 13-year-old male, originally from Canada and residing in Portugal for the past two years, was referred to the Pediatric Endocrinology consultation for evaluation of short stature (height 141.6cm, 1st percentile, -2.13 SDS; weight 39.9 kg; 25st percentile, -0.72 SDS).His gestation was uneventful, and his early developmental milestones were reported to be within normal limits. He is currently integrated into the Portuguese school system and benefits from individualized educational support.The patient has a personal history of congenital sensorineural hearing loss and has been using hearing aids since 14 months of age, which have allowed him to develop functional communication skills.On physical examination, several striking phenotypic features were observed. These included a frontal white forelock, intensely blue irises, and evident distopia canthorum. No family history of similar physical features was reported by the parents.Endocrine evaluation revealed normal growth hormone function, and the patient was in the early stages of puberty, consistent with his chronological age. Given the presence of these unusual phenotypic characteristics, he was referred for comprehensive genetic evaluation. Genetic testing ultimately identified a mutation in the PAX3 gene, confirming the diagnosis of Waardenburg syndrome type I. Subsequent testing of both parents demonstrated that the mutation had arisen de novo, with neither parent carrying the same genetic alteration.Learning Points Discussion: Waardenburg syndrome is a rare genetic disorder with distinctive phenotypic features, including congenital sensorineural hearing loss, pigmentary abnormalities, and characteristic hair and ocular changes. Recognizing this typical phenotypic presentation is essential, as early identification allows timely audiological intervention, which can significantly improve developmental outcomes and quality of life.This case, supported by a clinical photograph illustrating the classic phenotype, highlights the importance of careful examination and clinical suspicion in diagnosing affected individuals, facilitating prompt management and genetic counseling for families.
