Aperçu: G.M.
Il
est reconnu que 5% à 10% des enfants avec macrocéphalie et trouble du spectre de l'autisme (TSA) et / ou du handicap
intellectuel (ID) ont une mutation pathogène hétérozygote dans le gène
suppresseur de tumeur PTEN qui est associé au syndrome tumoral du
hamartoma PTEN.
Les
données cliniques et moléculaires ont été recueillies et analysées chez
47 patients atteints de mutation PTEN de 38 familles éligibles. La
macrocéphalie (circonférence de la tête moyenne de + 5,7 SD) avec
retard de développement, ID et / ou TSA était le signe / symptôme le
plus fréquent (66%). Les caractéristiques cliniques comprenaient des résultats
dermatologiques (66%), des symptômes gastro-intestinaux (GI) (34%), un
diagnostic de TSA (50%), une anomalie de l'imagerie cérébrale (53% de ceux
examinés) et une anomalie de l'imagerie thyroïdienne (26%).Il
s'agit du plus grand sondage sur les caractéristiques cliniques chez
les enfants atteints de mutations pathogènes PTEN à ce jour. Il confirme des rapports antérieurs sur l'augmentation des taux de troubles du développement neurologique. Les
anomalies dermatologiques, gastro-intestinales et thyroïdiennes
dépendent de l'âge et peuvent ne pas être présentes au moment du
diagnostic, nécessitant un suivi régulier et une surveillance médicale.
Le diagnostic pédiatrique précoce est important pour l'établissement
d'une surveillance médicale et de développement ainsi que pour le
dépistage d'autres membres de la famille à risque.
J Med Genet. 2017 May 19. pii: jmedgenet-2016-104484. doi: 10.1136/jmedgenet-2016-104484.
A retrospective chart review of the features of PTEN hamartoma tumour syndrome in children
Hansen-Kiss E1, Beinkampen S2, Adler B3, Frazier T4, Prior T5, Erdman S6,7, Eng C8,9, Herman G2,6.
Author information
- 1
- Center for Molecular and Human Genetics, Nationwide Children's Hospital, Westerville, Ohio, USA.
- 2
- Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
- 3
- Department of Radiology, The Ohio State University, Columbus, Ohio, USA.
- 4
- Center for Autism, Cleveland Clinic Children's, Cleveland, Ohio, USA.
- 5
- Department of Medical Genetics, Ohio State University, Columbus, USA.
- 6
- Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
- 7
- Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus, Ohio, USA.
- 8
- Cleveland Clinic Genomic Medicine Institute, Ohio, USA.
- 9
- Genetics and Genomics Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Abstract
OBJECTIVE:
It is recognised that 5% - 10 % of children with macrocephaly and autism spectrum disorder (ASD) and/or intellectual disability (ID) have a heterozygous pathogenic mutation in the PTEN tumour suppressor gene that is associated with PTEN hamartoma tumour syndrome. However, the clinical features and course in children with a pathogenic PTEN mutation are unclear and have not been well documented.STUDY OBJECTIVES:
We undertook a retrospective chart review of children (< 18 years) with pathogenic PTEN mutations to ascertain clinical findings, clinical course and possible outcomes.RESULTS:
Clinical and molecular data were collected and analysed for 47 patients with PTEN mutation from 38 eligible families. Macrocephaly (average head circumference of + 5.7 SD) with developmental delay, ID and/or ASD were the most common presenting signs/symptoms (66 %). Clinical features included dermatological findings (66 %), gastrointestinal (GI) symptoms (34 %), ASD diagnosis (50 %), abnormal brain imaging (53 % of those examined) and abnormal thyroid imaging (26 %).CONCLUSIONS:
This is the largest survey of clinical features in children with PTEN pathogenic mutations to date. It confirms earlier reports of increased rates of neurodevelopmental disorders. Dermatological, GI and thyroid abnormalities are age dependent and may not be present at the time of diagnosis, requiring regular monitoring and medical surveillance. Early paediatric diagnosis is important for institution of medical and developmental surveillance as well as for testing other at- risk family members.
© Article author(s) (or
their employer(s) unless otherwise stated in the text of the article)
2017. All rights reserved. No commercial use is permitted unless
otherwise expressly granted.
- PMID: 28526761
- DOI: 10.1136/jmedgenet-2016-104484
