Inherited macrocephaly-hamartoma syndromes

Area of Science:

• Genetics and Molecular Biology
• Syndromology
• Cancer Predisposition Syndromes

Background:

• The phosphatase and tensin homolog (PTEN) gene, located on chromosome 10q22-23, plays a crucial role in cell growth and tumor suppression.
• Previously, several distinct clinical syndromes were recognized, including Cowden syndrome, Bannayan-Zonana syndrome, Riley-Ruvalcaba syndrome, and Lhermitte-Duclos syndrome, along with benign familial macrocephaly and external hydrocephalus.

Purpose of the Study:

• To present molecular and clinical evidence supporting the unification of several distinct syndromes into a single entity.
• To propose a new nomenclature for this unified syndrome based on its characteristic clinical features.

Main Methods:

• Review and synthesis of recent molecular biology findings related to the PTEN locus.
• Analysis of clinical data from patients diagnosed with the aforementioned syndromes.
• Correlation of genetic findings with observed phenotypic abnormalities.

Main Results:

• Evidence strongly supports unifying Cowden and Bannayan-Zonana syndromes.
• The findings also strongly suggest including Riley-Ruvalcaba syndrome, Lhermitte-Duclos syndrome, benign familial macrocephaly, and external hydrocephalus under this unified entity.
• A new nomenclature, PTEN MATCHS (macrocephaly, autosomal dominant, thyroid disease, cancer, hamartomata, skin abnormalities) syndrome, is proposed.

Conclusions:

• The PTEN gene is central to a spectrum of related disorders previously considered separate.
• The proposed PTEN MATCHS syndrome provides a unified framework for understanding and diagnosing these conditions.
• This unification facilitates a more cohesive approach to research, diagnosis, and management of patients with PTEN-related disorders.