Neuroradiological Findings in Noonan Syndrome: a multicentric Italian study

Giuseppa Patti; Maiorano Nadia Gabriella; Francesca Piccoli; Calevo Maria Grazia; Federica Tamburrino; Emanuela Scarano; Concetta Schiavarello; Eleonora Orlandini; Gabriella Pozzobon; Cristina Baldoli; Martina Finamore; Anna Grandone; Francesca Aiello; Mario Cirillo; Domenico Corica; Margherita Wasniewska; Alessandro Cattoni; Paolo Remida; Donatella Capalbo; Fabio Tortora; Sara Azzolini; Mariam Mansour; Faienza Maria Felicia; Stefano Palladino; Flavia Napoli; Alessia Angelelli; Iorgi Natascia Di; Andrea Rossi; Mohamad Maghnie; Mariasavina Severino

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ESPE Abstracts (2024) 98 RFC5.3

ESPE2024 Rapid Free Communications Growth and Syndromes (6 abstracts)

Neuroradiological Findings in Noonan Syndrome: a multicentric Italian study

Giuseppa Patti ^1,2 , Nadia Gabriella Maiorano ¹ , Francesca Piccoli ³ , Maria Grazia Calevo ⁴ , Federica Tamburrino ⁵ , Emanuela Scarano ⁵ , Concetta Schiavarello ⁵ , Eleonora Orlandini ⁶ , Gabriella Pozzobon ⁷ , Cristina Baldoli ⁸ , Martina Finamore ⁷ , Anna Grandone ⁹ , Francesca Aiello ⁹ , Mario Cirillo ¹⁰ , Domenico Corica ¹¹ , Margherita Wasniewska ¹¹ , Alessandro Cattoni ¹² , Paolo Remida ¹³ , Donatella Capalbo ¹⁴ , Fabio Tortora ¹⁵ , Sara Azzolini ¹⁶ , Mariam Mansour ¹⁷ , Maria Felicia Faienza ¹⁸ , Stefano Palladino ¹⁹ , Flavia Napoli ¹ , Alessia Angelelli ¹ , Natascia Di Iorgi ^1,2 , Andrea Rossi ³ , Mohamad Maghnie ^1,2 & Mariasavina Severino ³

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¹Department of Pediatrics, IRCCS Istituto Giannina Gaslini, Genova, Italy. ²Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health - University of Genova, Genova, Italy. ³Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy. ⁴IRCCS Giannina Gaslini, Genova, Italy. ⁵Rare Diseases Unit, Department of Pediatrics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. ⁶università di Bologna, Bologna, Italy. ⁷Pediatric Clinic, IRCCS San Raffaele Hospital, Università Vita-Salute San Raffaele, Milano, Italy. ⁸Neuroradiology Unit, San Raffaele Hospital, Università Vita-Salute San Raffaele, Milan, Italy., Milano, Italy. ⁹Department of Child, Woman, General and Specialized Surgery, University of Campania L. Vanvitelli, Napoli, Italy. ¹⁰Department of Advanced Medical and Surgical Sciences, University of Campania Vanvitelli, Napoli, Italy. ¹¹Department of Human Pathology of Adulthood and Childhood, Unit of Pediatrics, University of Messina, Messina, Italy, Messina, Italy. ¹²Department of Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. ¹³Department of Neuroradiology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. ¹⁴Department of Translational Medical Sciences, Paediatric Endocrinology Unit, University "Federico II", Napoli, Italy. ¹⁵Department of Advanced Biomedical Sciences, University Federico II Naples, Napoli, Italy. ¹⁶Pediatric Department, San Bortolo Hospital, Vicenza, Italy. ¹⁷Neuroradiology Department, San Bortolo Hospital, Vicenza, Italy. ¹⁸Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari “Aldo Moro”, Bari, Italy. ¹⁹Radiology Unit, Pediatric Hospital Giovanni XXIII, Bari, Italy

Background: Data on the neuroradiological findings in Noonan syndrome (NS) are limited.

Study Design and participants: Multicentric retrospective observational study conducted in 9 Italian centers of Pediatric Endocrinology. Population includes 112 patients (62 males, 50 females; 73 PTPN11, 8 KRAS, 8 SOS1, 4 LZTR1, 4 RIT1, 4 SHOC2, 3 BRAF, 2 RAF1, 1 ERF, 1 HRAS, 1 MAP2K1, 1 MEK1, 1 PPP1CB, 1 RASA1) with diagnosis of NS genetically confirmed.

Methods: Brain magnetic resonance (MRI) was performed between January 2009 and May 2023. Neuroimaging studies were reviewed in consensus by two neuroradiologists in a tertiary university center for presence of brain, spine, pituitary and cranio-cervical junction malformations, Chiari I anomaly, syrinx, brain tumors and vascular anomalies. Overall, 203 brain MRI and additional 33 spinal MRI studies were reviewed in 112 subjects (mean age at last MRI: 10.6 years, range 8months-31years).

Results: Callosal anomalies (n = 44 hypo-dysplasia, n = 5 complete agenesis, n = 4 hyperplasia) were detected in 53/112 subjects (47.3%). In 51/112 (45,5%), there was mild to moderate white matter volume loss with enlargement of the lateral ventricles. In 56/112 (50%) cases, there were midbrain-hindbrain anomalies (n = 49 pontine hypoplasia, n = 27 inferior vermis hypoplasia). Chiari I anomaly was detected in 13/112 cases (11.6%), while cranio-cervical junction anomalies were found in 31% of subjects. Cerebrovascular anomalies included: intracranial and/or extracranial arterial tortuosity (n = 38), aneurysms (n = 4), cavernoma (n = 4), stroke (n = 3), moyamoya-like collaterals (n = 2), and arterial stenosis (n = 1). A brain tumor (DNET, germinoma) was associated in 9/112 cases (9%). Four subjects (3.5%) had a syrinx while 6 (5%) had a low-lying spinal cord.

Conclusion: The high percentage of neuroradiological abnormalities in our NS cohort suggests the need for brain MRI in clinical practice in NS patients. More data are required in a larger cohort to better understand the impact of neuroradiological involvement in NS and the correlation between genotype and neuroradiological phenotype.