Claudia Ciaccio1, Veronica Saletti2, Stefano D'Arrigo3, Silvia Esposito2, Enrico Alfei2, Isabella Moroni4, Davide Tonduti4, Luisa Chiapparini5, Chiara Pantaleoni2, Donatella Milani6. 1. Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. Electronic address: claudia.ciaccio@unimi.it. 2. Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 3. Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. Electronic address: stefano.darrigo@istituto-besta.it. 4. Child Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 5. Neuroradiology Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 6. Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Abstract
OBJECTIVE OF THE STUDY: To give a full overview of the clinical presentation of PTEN mutations in pediatric patients and to propose a pediatric follow-up protocol. METHODS: Recruitment of 16 PTEN mutated children (age 6 months-11 years) from two pediatric centers in Milan (Italy) between 2006 and 2017. All the patients underwent clinical and neurologic evaluations, cognitive and behavioral tests, and brain MRI; they are currently following an oncologic follow-up. RESULTS: Extreme macrocephaly is present in all the patients (69% HC above +4 SD). Neuropsychiatric issues have high prevalence, with 56% of patients showing developmental delay and 25% showing autism spectrum disorder. Brain MRI reveals in 75% of the patients at least one of the following: enlarged perivascular spaces, white matter anomalies, and/or downward displacement of the cerebellar tonsils through the foramen magnum, resulting in Chiari I malformation in two patients. Vascular malformations have a prevalence of 19%, with further evidence that complex cardiovascular malformations may be related to PTEN mutations; 31% of patients present hamartomas. None of our patients have so far experienced any oncologic complication. CONCLUSIONS: We suggest to screen for PTEN mutations all children presenting macrocephaly and one of the following: neurodevelopmental issues, one of the three major brain MRI anomalies, cutaneous lesions, vascular malformations, family history positive for PTEN related malignancies; or also with macrocephaly alone when exceeding +3 SD. Basing on our cohort results and further recent studies on the condition, we recommend a follow-up protocol that includes annual clinical and dermatological examination, thyroid and abdominal US, and Fecal Occult Blood test plus neurodevelopmental evaluation, heart US (to exclude congenital heart malformations), and brain MRI (to exclude Chiari I malformation) at diagnosis.
OBJECTIVE OF THE STUDY: To give a full overview of the clinical presentation of PTEN mutations in pediatric patients and to propose a pediatric follow-up protocol. METHODS: Recruitment of 16 PTEN mutated children (age 6 months-11 years) from two pediatric centers in Milan (Italy) between 2006 and 2017. All the patients underwent clinical and neurologic evaluations, cognitive and behavioral tests, and brain MRI; they are currently following an oncologic follow-up. RESULTS:Extreme macrocephaly is present in all the patients (69% HC above +4 SD). Neuropsychiatric issues have high prevalence, with 56% of patients showing developmental delay and 25% showing autism spectrum disorder. Brain MRI reveals in 75% of the patients at least one of the following: enlarged perivascular spaces, white matter anomalies, and/or downward displacement of the cerebellar tonsils through the foramen magnum, resulting in Chiari I malformation in two patients. Vascular malformations have a prevalence of 19%, with further evidence that complex cardiovascular malformations may be related to PTEN mutations; 31% of patients present hamartomas. None of our patients have so far experienced any oncologic complication. CONCLUSIONS: We suggest to screen for PTEN mutations all children presenting macrocephaly and one of the following: neurodevelopmental issues, one of the three major brain MRI anomalies, cutaneous lesions, vascular malformations, family history positive for PTEN related malignancies; or also with macrocephaly alone when exceeding +3 SD. Basing on our cohort results and further recent studies on the condition, we recommend a follow-up protocol that includes annual clinical and dermatological examination, thyroid and abdominal US, and Fecal Occult Blood test plus neurodevelopmental evaluation, heart US (to exclude congenital heart malformations), and brain MRI (to exclude Chiari I malformation) at diagnosis.
Authors: Julia A Baran; Steven D Tsai; Amber Isaza; Garrett M Brodeur; Suzanne P MacFarland; Kristin Zelley; Denise M Adams; Aime T Franco; Andrew J Bauer Journal: Horm Res Paediatr Date: 2021-04-22 Impact factor: 2.852
Authors: Mirko Uljarević; Thomas W Frazier; Gaëlle Rached; Robyn M Busch; Patricia Klaas; Siddharth Srivastava; Julian A Martinez-Agosto; Mustafa Sahin; Charis Eng; Antonio Y Hardan Journal: J Autism Dev Disord Date: 2021-02-17
Authors: Mirko Uljarević; Thomas W Frazier; Gaëlle Rached; Robyn M Busch; Patricia Klaas; Siddharth Srivastava; Julian A Martinez-Agosto; Mustafa Sahin; Charis Eng; Antonio Y Hardan Journal: Am J Med Genet A Date: 2021-08-23 Impact factor: 2.802
Authors: Lamis Yehia; Marilyn Seyfi; Lisa-Marie Niestroj; Roshan Padmanabhan; Ying Ni; Thomas W Frazier; Dennis Lal; Charis Eng Journal: JAMA Netw Open Date: 2020-01-03
Authors: Thomas W Frazier; Ritika Jaini; Robyn M Busch; Matthew Wolf; Tammy Sadler; Patricia Klaas; Antonio Y Hardan; Julian A Martinez-Agosto; Mustafa Sahin; Charis Eng Journal: Mol Autism Date: 2021-01-28 Impact factor: 7.509