Dados do Trabalho

Título

DEVELOPMENTAL DISORDERS ASSOCIATED WITH PTEN GENE: CASE SERIES REPORT

Apresentação do caso

CASE 1:
A boy with developmental delay and congenital macrocephaly, evolving with dysphagia and airway hypotonia. Complete exome sequencing was performed with detection of pathogenic variant in the PTEN gene (c.737C>T).

CASE 2: Premature boy, with delayed development of departure, macrocephaly and ephelides in the foreskin. He developed nodular hyperplasia in ileum and painful amplification syndrome with pharmacoresistant pain. Sequencing of the PTEN gene detected an intragenic deletion.

CASE 3:
Girl with autism spectrum disorder identified at 17 months. Neurological examination with central hypotonia and macrocephaly. Magnetic resonance imaging of the skull identified craniofacial disproportion and confluent foci of hypersignal in white matter, suggestive of mucopolysaccharidosis. The panel sequence for leukodystrophy, identific orpathogenic variant in the PTEN c.388 C>G gene.

Discussão

PTEN (phosphatase and tensin homologue) is a tumor suppressor gene, responsible for the production of a protein of the same name capable of regulating the cell cycle.
Variants in the PTEN gene are associated with PTEN-hamartoma tumor syndrome (PHTS) characterized by a significant increase in the chance of developing neoplasms, as well as trikylemomas, hamartomas, lipomas, thyroid nodules, macrocephaly, cerebrovascular malformations, ephelides in foreskin, as well as developmental delay, intellectual disability, and autism spectrum disorder.
Among neurodevelopmental disorders, non-tumor manifestations were extremely relevant in the diagnosis, and all patients had macrocephaly.
The relevance of this diagnosis is also in genetic counseling, since it has autosomal dominant inheritance. It is essentialthat carriers of mutations in the PTEN gene be regularly monitored for the development of neoplasms and complications associated with PHTS.

Comentários finais

The reported cases illustrate the importance of clinical suspicion for the diagnosis of PTEN-related syndromes in the presence of a child with macrocephaly and neurodevelopmental disorder, regardless of the presence of tumor lesions. Once identified, affected patients and parents should be periodically screened for the development of tumors and oriented about the risk of recurrence in their offspring.

Referências (se houver)

1) RESERVADOS, I. U. -- T. O. D. Orphanet: PTEN. Disponível em: <https://www.orpha.net/consor/cgi-bin/Disease_Genes.php?lng=PT&data_id=15166&MISSING%20CONTENT=PTEN&search=Disease_Genes_Simple&title=PTEN>. Acesso em: 15 jul. 2022.
2‌) LIMA, E. U. DE et al. Nova mutação no gene PTEN em um paciente brasileiro com síndrome de Cowden. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 56, p. 592–596, 1 nov. 2012.
3‌) PTEN Hamartoma Tumor Syndrome | Boston Children’s Hospital. Disponível em: <https://www.childrenshospital.org/conditions/pten-hamartoma-tumor-syndrome>. Acesso em: 14 jul. 2022.
4) ENG, C. PTEN Hamartoma Tumor Syndrome. Disponível em: <https://www.ncbi.nlm.nih.gov/books/NBK1488/>.

Fonte de Fomento (se houver)

Declaração de conflito de interesses de TODOS os autores

Não houve declaração de conflitos de nenhum dos autores.

Área

Neurogenética