Noonan Syndrome and Rett Syndrome in An 8-Year-Old Girl With A Tectal Neoplasm

Individuals with Noonan syndrome (NS) are predisposed to hematologic cancers, solid tumors, and low-grade gliomas. We report an 8-year-old girl originally referred at age 14 months for short stature, developmental delay, and failure to thrive who was subsequently found to have pathogenetic variants both in MECP2 and PTPN11. Family history included a maternal half-sister with NS and a mother carrying the PTPN11 mutation. Familial single-gene testing showed a heterozygous pathogenic variant in PTPN11 (c.417G > C p.Glu139Asp) suggesting NS, prompting initiation of growth hormone (GH) treatment at 26 months. Due to associated language delays, gross motor delays, microcephaly, and seizures, exome sequencing (ES) was pursued. ES identified a heterozygous de novo pathogenic variant (c.763C > T p.Arg255Ter) in MECP2 and led to the additional diagnosis of Rett syndrome (RTT). Seizure onset prompted neuroimaging, which demonstrated hydrocephalus due to aqueductal stenosis secondary to a tectal neoplasm. GH treatment was discontinued. The co-occurrence of NS and RTT is rare. ES enabled the additional diagnosis of RTT in our patient with NS, who presented with atypical features and developmental regression.