Expanding the Phenotypic Spectrum of DICER1 Syndrome: Case Report with Overgrowth, Macrocephaly, Multinodular Goiter, and Lung Cyst.

Background

DICER1 syndrome is an autosomal dominant disorder with reduced penetrance and variable expressivity, predisposing carriers to a broad spectrum of benign and malignant tumors as well as non-neoplastic features. Recent reports suggest an expanded phenotype overlapping with GLOW syndrome, characterized by developmental anomalies in addition to tumor risk. Case Presentation: We describe a 16-year-old male with overgrowth, macrocephaly, developmental delay, multinodular goiter, and a unilateral lung cyst. Genetic testing identified a germline heterozygous nonsense variant in DICER1 (c.1525C>T, p.Arg509Ter), confirmed also in the patient's mother. Family history included thyroid nodules, uterine tumor, and multiple malignancies on both maternal and paternal sides. The proband has remained free of neoplasia to date, and his lung cyst is stable under annual imaging surveillance. Discussion: The presented patient highlights the expanding phenotypic spectrum of DICER1-associated conditions, with features overlapping with GLOW syndrome but without Wilms tumor or cystic nephroma. The absence of malignancy in both the proband and his mother underscores the reduced penetrance and variable expressivity of DICER1 variants. Our findings reinforce the importance of structured surveillance, individualized risk assessment, and cautious management of asymptomatic carriers.

Conclusions

This report expands the clinical spectrum of DICER1 syndrome, supporting its recognition as both a tumor predisposition and developmental disorder. Longitudinal studies are required to refine surveillance strategies and better define genotype-phenotype correlations.