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Infantile macrocephaly and multiple subcutaneous lipomas diagnosed with PTEN hamartoma tumor syndrome: A case report
Yuka Yotsumoto1,2, Atsuko Harada2,3, Jiro Tsugawa4
1Department of Pediatrics, Takatsuki General Hospital, Takatsuki, Osaka 569-1192, Japan.
Insights
A PTEN gene mutation caused macrocephaly and developmental delay in an infant. Further monitoring is needed for potential tumor development and psychomotor changes.
Area of Science:
- Genetics
- Pediatrics
- Oncology
Background:
- Heterozygous loss-of-function mutations in the PTEN gene, a tumor suppressor, lead to various disorders.
- PTEN hamartoma tumor syndrome and Cowden disease, linked to PTEN mutations, primarily affect adolescents and young adults with thyroid and breast cancer.
- This case highlights a rare presentation in an infant with macrocephaly and early-onset lipoma.
Purpose of the Study:
- To report a case of a male infant diagnosed with a PTEN gene mutation.
- To investigate the clinical manifestations, including macrocephaly, lipoma, and developmental delay.
- To analyze the PTEN expression in the resected lipoma and discuss its implications.
Main Methods:
- Clinical case presentation and follow-up.
- Genetic analysis to identify germline PTEN mutation (NM_000314.7, c.195C>A, p.Y65*).
- Immunohistochemistry to assess PTEN expression in the resected lipoma.
Main Results:
- An 8-month-old infant with macrocephaly developed a lipoma and was diagnosed with a pathogenic PTEN germline mutation at 2 years and 9 months.
- The patient exhibited developmental delay and autism spectrum disorder by age 5.
- Immunohistochemistry showed PTEN expression in the lipoma similar to normal adipose tissue, suggesting a lack of a 'two-hit' mechanism for lipoma growth.
Conclusions:
- Germline PTEN mutations can manifest in infancy with macrocephaly, lipoma, and developmental disorders, including autism spectrum disorder.
- The rapid growth of the lipoma in this case may not be directly related to a PTEN 'two-hit' mechanism.
- Long-term follow-up is crucial for monitoring psychomotor development and potential tumor formation in individuals with PTEN mutations.
Abstract:
A heterozygous loss-of-function mutation of the PTEN gene, one of the tumor suppressor genes, causes a wide variety of disorders, ranging from macrocephaly/autism syndrome to PTEN hamartoma tumor syndrome, including Cowden disease that causes thyroid and breast cancer mainly in the adolescence and young adult generation. An 8-month-old male infant with simple macrocephaly developed a café-au-lait spot and two subcutaneous tumors at the age of 1 year. One of the tumors developed rapidly was resected at the age of 1 year and 9 months and identified as benign lipoma. From the age of 2 years, the patient often threw a tantrum. At the age of 2 years and 9 months, a pathogenic germline mutation was identified in the PTEN gene (NM_000314.7), c.195C>A, p.Y65* in the form of a heterozygous germline variant. Developmental delay was noted but no tumors were found in the thyroid gland and breasts. Immunohistochemistry for PTEN in the resected lipoma demonstrated that the PTEN expression pattern was similar to that in a subcutaneous adipose tissue from a normal subject, suggesting that two-hit was not likely involved in the rapid growth of this lipoma. At the age of 5 years, the patient was diagnosed with autism spectrum disorders with moderate developmental delay. A long-term follow-up is underway to examine developmental changes in psychomotor disorders and possible tumor formation.
