The syndrome of sporadic goitre and congenital deafness.

INTRODUCTION

RNU4ATAC-opathy is a rare autosomal recessive disorder characterized by a wide clinical spectrum, including brain anomalies, seizures, strokes, immunodeficiency, and cardiac defects. Other manifestations include ophthalmologic, dermatologic, renal, gastrointestinal, auditory, and endocrine involvement. Here, we report the identification of pathogenic RNU4ATAC variants through whole exome sequencing in an infant presenting with microcephaly, growth failure, and immunodeficiency.

CASE PRESENTATION: We describe an 11-month-old infant who had been followed since 4 months of age for growth failure and developmental delay. During follow-up, the patient experienced episodes of neurological deterioration triggered by febrile illnesses associated with SARS-CoV-2 and respiratory syncytial virus infections (RSV) at 9 and 11 months of age, respectively. Immunological evaluation showed normal immunoglobulin levels, a marked reduction in switched memory and memory B cells, impaired T-cell activation, and decreased T-cell subpopulations, suggesting combined immunodeficiency that may have contributed to increased susceptibility to viral infections. Whole exome sequencing subsequently identified compound heterozygous pathogenic variants in the RNU4ATAC gene, confirming the diagnosis of RNU4ATAC-opathy.

DISCUSSION: RNU4ATAC-opathy should be considered in cases with microcephaly, growth failure, immunodeficiency, and skeletal abnormalities. Our case shows that RNU4ATAC-opathy may present as infection-related encephalopathy, together with combined T- and B-cell dysfunction. Early immunological assessment and timely initiation of prophylactic therapy could play a key role in improving survival. Genetic and immunological evaluations are essential for accurate diagnosis, early intervention, and effective management. Further research is needed to clarify the syndrome's impact on immune function and guide targeted therapies.