SUN-110 Noonan Syndrome and Rett Syndrome in an 8-Year-Old Girl With a Tectal Glioma

Abstract N. Shetty: None. J. Rogg: None. R. Lulla: None. K. Svokos: None. L. Massingham: None. J.Q. Quintos: None. Background: The co-occurrence of Noonan Syndrome (NS) and Rett Syndrome (RTT) is rare and has not previously been reported. Individuals with NS are predisposed to hematologic cancers, solid tumors, and low-grade gliomas. We report an 8-year-old female with NS due to PTPN11 mutation who was on GH therapy and later diagnosed with RTT due to MECP2 mutation. She later developed a tectal glioma leading to discontinuation of the GH treatment. Method: Case report. Results: A 22-month-old female born small for gestational age (SGA) (37 weeks; BW 4 lbs 10 oz; BL 17 in) was seen in the endocrine clinic for evaluation of short stature. She has a maternal half-sister with NS with PTPN11 mutation. Physical examination showed a length of 70.1 cm (<1%; z = -4.6), weight of 6.71 kg (<1%; z = -4.3), head circumference of 39 cm (z = -5.6), and Tanner 1 puberty. Patient also displayed severe hypotonia with head lag (characteristic of RTT), profound developmental delays, and facial features such as broad forehead, low-set ears, down slanting palpebral fissures (characteristic of NS). Laboratory evaluation at 14 months showed IGF-1 levels of 24 ng/ml (Normal (N): 56-144 ng/ml) and IGF-BP3 levels of 0.5 mg/L (N: 0.8-3 mg/L). Family genetic testing revealed a heterozygous variant in PTPN11 (c.417G>C (p.Glu139Asp)) diagnostic for NS. Growth hormone stimulation using arginine and clonidine showed peak growth level of 11 ng/ml. At 2 years and 3 months, she began GH treatment at a dose of 0.33 mg/kg/week. Because her phenotype is not typical of NS (significant FTT, IUGR, microcephaly, and regression), whole exome sequencing was done and showed a heterozygous de novo variant in MECP2 (c.763C>T (p.R255x)), confirming RTT at 2 years and 7 months. At 2 years and 9 months, patient had new onset seizure activity and was prescribed anticonvulsant; brain MRI showed normal findings. At 4 years and 11 months, height was 89.5 cm (<1%; z= -4.1), weight was 11.1 kg (<1%; z= -4.65), and growth velocity 7.7 cm/year. At 5 years and 6 months, patient displayed worsening seizure activity. Brain MRI showed tectal mass causing aqueductal stenosis with associated hydrocephalus. Following a right endoscopic third ventriculostomy, ventricle size stabilized and the tectal lesion was redemonstrated. Due to diagnosis of low-grade glioma, GH treatment was discontinued. Conclusion: The co-occurrence of NS and RTT is rare. Genetics evaluation is needed in children with NS exhibiting atypical features such as developmental regression. NS patients require close monitoring for the development of cancers including hematologic, solid tumors, and brain tumors. The development of tectal glioma in this patient necessitated the discontinuation of GH treatment. Sunday, June 2, 2024