Distinctive facies, macrocephaly, and developmental delay are signs of a PTEN mutation in childhood

Kohji Kato, Seiji Mizuno, Mie Inaba, Shinobu Fukumura, Naoko Kurahashi, Koichi Maruyama, Daisuke Ieda, Kei Ohashi, Ikumi Hori, Yutaka Negishi, Ayako Hattori, Shinji Saitoh

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Background: Germline mutations of the PTEN gene are responsible for several PTEN hamartoma tumor syndromes. They are also implicated as a cause of macrocephaly and mild to severe developmental delay, regardless of the presence or absence of hamartomas in childhood. Nevertheless, because of limited information, the clinical features present during childhood in patients with a PTEN mutation are yet to be elucidated. Methods: PTEN mutations were investigated by multiplex targeted sequencing of genomic DNA from 33 children with increased head circumference (>+2 SD) and developmental delay. The clinical features of all the patients with a PTEN mutation were abstracted by dysmorphologists. Results: We have identified six children with a PTEN mutation. Clinical dissection of these six patients, in addition to patient reports in the literature, revealed distinctive facial features that included frontal bossing, dolichocephaly, horizontal eyebrows, and a depressed nasal bridge. Macrocephaly (+3.2 to +6.0 SD) was noticeable compared to their height (−0.8 to +2.1 SD), and the difference in the SD value of head circumference and height was more than 3 SD in all patients. Conclusion: The presence of distinctive facies, extreme macrocephaly with normal to mildly high stature, and developmental delay may be useful for identifying patients with a PTEN mutation in childhood. Early identification of patients with a PTEN mutation would help uncover the natural course of tumor development in this group of individuals who have a possible predisposition to cancer, and be important for the development of an optimal surveillance strategy.

Original languageEnglish
Pages (from-to)678-684
Number of pages7
JournalBrain and Development
Issue number8
Publication statusPublished - Sept 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology


Dive into the research topics of 'Distinctive facies, macrocephaly, and developmental delay are signs of a PTEN mutation in childhood'. Together they form a unique fingerprint.

Cite this