Genetic, somatic and psychological characteristics of adult patients with Noonan syndrome

Objectives: Noonan syndrome (NS) is a genetic disorder with a prevalence of 1 in 1000-2500 live births. Inheritance is mainly autosomal dominant, but de novo mutations are common. NS is characterized by short stature, facial dysmorphisms and a variety of somatic abnormalities. Indications are found for impairment in affective processing, inadequate social behaviour and increased anxiety. Virtually no studies focus on the interaction between genetic etiology and somatic and/or neuropsychiatric phenotype. Methods: In the present study, genetic etiologies, somatic comorbidity and neuropsychological/neuropsychiatric phenotype were investigated in a group of 38 adult Noonan patients mean age 28,7). All relevant information about medical and developmental history was documented. Apart from genetic subtyping, a somatic and neurological workup was performed. All patients underwent a thorough neuropsychological and neuropsychiatric examination using standardized instruments. Results: A de novo mutation was present in about half of the patients. In most of the remaining patients the disease was inherited via the mother. Genetic subtyping demonstrated a mutation in PTPN11 in 21 patients and a mutation in SOS1 and KRAS in both 2. In the other 13 patients, the results of genetic analysis are not available as yet. Somatic comorbidity concerned mainly pulmonary valve stenosis and bleeding abnormalities. Although major psychiatric disorders were virtually absent, neuropsychological tests revealed problems with emotion identification and verbalisation in a substantial number of patients. Discussion: The neuropsychological phenotype of NS is characterized by alexithymia. It is at present unclear whether deficits in emotional recognition are related with a specific genetic subtype