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Abstract Details

A First Case of Noonan Syndrome SOS2 related with Leukodystrophy, Disseminated Neurofibromas and Polyneuropathy
Child Neurology and Developmental Neurology
P5 - Poster Session 5 (8:00 AM-9:00 AM)
5-015
We present a first case of Noonan syndrome in a 19 years old transgender male with a missense SOS2 mutation with severe neurological presentation including leukodystrophy, neurofibromas and axonal polyneuropathy with secondary demyelinating features.
Noonan syndrome with SOS2 mutation has only been described with normal neurologic features and mild learning difficulties. Here we describe a patient with severe neurologic manifestations thus expanding the knowledge and phenotype associated with SOS2 related Noonan syndrome.
The diagnosis of Noonan syndrome for this patient took many years. Karyotype was 46XX. PTNP11, KRAS, RAF, MAP2K1, MAP2K2, HRAS, MEK1, MEK2, NRAS, NF1, NF2, SPRED, RIT1 mutations were all negative, as was the MtDNA/depletion integrity panel for MNGIE. We found a missense variant of SOS2, c.800T>A (p.Met267Lys), heterozygous with autosomal dominant inheritance using whole exome sequencing.
Our patient had dysmorphic facial features, small stature, hypertrophic cardiomyopathy, lymphatic dysplasia, global development delay as well as skin findings seen in rasopathies such as Costello or Cardiofaciocutaneous syndrome. Familial history was negative. Neuropsychiatric features of our patient included ADHD, autism spectrum disorder, depression, anxiety and gender dysphoria. He suffered from C2 syringomyelia and axonal sensorimotor polyneuropathy with secondary demyelinating features. He had severe muscle atrophy making him wheelchair bound. He had no epilepsy while cerebral MRI showed bilateral diffuse bifrontoparietal leukodystrophy. Whole spinal MRI showed numerous bilateral neurofibromas.
This is the first case of SOS2 related rasopathy causing a rare but severe phenotype with neuropsychiatric disorders as well as syringomyelia, polyneuropathy, leukodystrophy and diffuse nerve root neurofibromas. This is a first demonstration that SOS2 mutations can behave like other mutations of the RAS-MAP-kinase pathway such as other Rasopathies giving rise to pathology in the integumentary system, cardiac system and neurological system.
Authors/Disclosures
Claudie Gauvreau, MD (Clinique Médicale Sainte-Julie)
PRESENTER 		No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Nicolas Chrestian, MD Dr. Chrestian has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Chrestian has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Chrestian has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Peer choice.