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Case Report: Smith-Magenis syndrome with bilateral high-grade vesicoureteral reflux, hypothyroidism, and seizure in infancy

Year: 2026

Type: article

Abstract: Smith-Magenis syndrome (SMS) is a rare neurodevelopmental and multisystem disorder caused mainly by 17p11.2 deletions involving RAI1. Because the characteristic behavioral and sleep phenotype may not yet be apparent, diagnosis in infancy can be challenging. We report a 9-month-old boy with recurrent febrile urinary tract infection, bilateral hydronephrosis with ureteral dilatation, hypothyroidism, global developmental delay, hypotonia, brachydactyly, dysmorphic features, phimosis, and short penis. Voiding cystourethrography demonstrated bilateral grade IV vesicoureteral reflux (VUR). Renal scintigraphy showed focal right renal cortical defects; DTPA effective renal plasma flow was 180.33 mL/min in the left kidney and 133.77 mL/min in the right kidney, corresponding to split function of 57.4% and 42.6%. Trio whole-exome sequencing with copy-number-variant analysis identified a de novo 3.63-Mb deletion at 17p11.2 encompassing RAI1, confirming SMS; a maternally inherited heterozygous DUOX2 likely pathogenic variant was also detected, but its contribution to hypothyroidism remains unproven. Infection improved with antibiotics, levothyroxine was resumed, and amoxicillin/clavulanate prophylaxis was initiated. Surgery for phimosis was postponed after an afebrile sleep-related seizure. Follow-up showed improved renal indices, no recurrent urinary tract infection, normalized thyroid function, and no definite abnormality on video-electroencephalography, although developmental delay persisted and brief seizure-like ocular events remained under evaluation. This case shows that high-grade bilateral VUR with recurrent infection and a syndromic neurodevelopmental phenotype can be an early presentation of SMS and warrants copy-number analysis, renal protection, and coordinated endocrine, neurologic, developmental, and urologic follow-up.

Source: Frontiers in Pediatrics

DOI: 10.3389/fped.2026.1906694

Authors: Yun Cheng, Xunwei Liu, Lingyun Yang, Jinwen Xu

Institution: Jiangnan University

Language: English

Topic: Genomic variations and chromosomal abnormalities

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801