Objective:

To document a case of central precocious puberty (CPP) as the primary clinical manifestation of a KMT2B-related disorder in a patient with concurrent X-linked ichthyosis (XLI), emphasizing the significance of this unique presentation.

Key Findings:

• The patient exhibited central precocious puberty without overt dystonia, marking a novel presentation for KMT2B-related disorders.
• Genetic analysis revealed a pathogenic KMT2B variant and STS deletion, highlighting the complexity of concurrent genetic conditions.
• GnRH analogue therapy was documented for CPP management in this context, suggesting a potential treatment pathway.

Interpretation:

KMT2B haploinsufficiency may lead to premature activation of the hypothalamic-pituitary-gonadal axis, underscoring the need for comprehensive endocrine assessment in children with KMT2B-related disorders to facilitate early diagnosis and intervention.

Limitations:

• The study is based on a single case report, limiting generalizability and the ability to draw broader conclusions.
• Long-term outcomes of the treatment and the full spectrum of clinical manifestations remain to be established, which may impact future clinical guidelines.

Conclusion:

This case expands the understanding of KMT2B-related disorders and highlights the importance of endocrine evaluation in affected children, advocating for further research into the implications of concurrent genetic conditions.