Genomic coordinate (human 10:87,863,625 PTEN) & (mouse 19:32,734,977 Pten).
Cytoband (human 10q23.31 PTEN) & (mouse 19qC1 Pten).
“Bannayan-Zonana Syndrome”, Victor McKusick, Mendelian Inheritance in Man’, 1966. (PTEN) icd10=Q87.89
INTRODUCTION.
Bannayan–Zonana syndrome is an overgrowth syndrome and hamartomatous disorder with occurrence of multiple subcutaneous lipomas, macrocephaly and hemangiomas.
The disease is inherited in an autosomal dominant manner. The disease belongs to a family of hamartomatous polyposis syndromes, which also includes: Peutz–Jeghers syndrome, Juvenile Polyposis, and Cowden syndrome.
Mutation of the PTEN gene underlies this syndrome, as well as Cowden syndrome, Proteus syndrome, and Proteus-like syndrome, these four (4) syndromes are referred to as PTEN Hamartoma-Tumor Syndromes.
Bannayan–Zonana syndrome is a genetic overgrowth disorder. It is part of the PTEN hamartoma tumor syndrome spectrum.
Core cause gene: PTEN (tumor suppressor).
Inheritance: Autosomal dominant.
Pathophysiology: Loss of PTEN function → dysregulated PI3K–AKT–mTOR signaling → tissue overgrowth and hamartomas.
Hallmark Clinical Features.
Bannayan–Zonana syndrome
is typically presents in infancy or childhood:
1. Macrocephaly.
Head circumference >97th percentile is very common
Often present at birth or early infancy
2. Hamartomatous growths.
Lipomas (fatty tumors)
Hemangiomas
Intestinal hamartomatous polyps → abdominal pain, bleeding, anemia
3. Developmental findings.
Developmental delay
Learning disabilities
Hypotonia
Autism spectrum features may occur
4. Pigmented penile macules.
Small dark spots on the glans penis
Highly characteristic but only present in males
Relationship to other PTEN syndromes.
Bannayan–Zonana syndrome overlaps genetically and clinically with:
Cowden syndrome
Proteus-like syndrome
PTEN-related autism with macrocephaly.
These conditions are now understood as variable expressions of PTEN mutation, rather than fully separate diseases.
Cancer risk.
Children: cancer risk is low
Adults: increased lifetime risk for:
Breast cancer
Thyroid cancer (especially follicular)
Endometrial cancer
Renal cell carcinoma
Colorectal cancer
Because of this, long-term surveillance is essential, even if childhood symptoms are mild.
Diagnosis.
Clinical suspicion: macrocephaly + hamartomas ± developmental delay
Confirmation: genetic testing showing a pathogenic PTEN mutation.
Management.
There is no cure, but care is proactive:
Multidisciplinary follow-up (genetics, neurology, gastroenterology)
Developmental and educational support
Regular cancer surveillance following PTEN guidelines
Symptomatic treatment (e.g., polyp management, lipoma excision).
Key takeaway:
Bannayan–Zonana syndrome is best understood not as an isolated syndrome, but as one pediatric presentation of PTEN hamartoma tumor syndrome, with implications that extend into adulthood.
There is evidence that Bannayan–Zonana syndrome is caused by mutation of the phosphatase-tensin homolog (PTEN) gene encoded on genomic coordinate 10:87,863,625 and cytoband 10q23.31 in humans.
