RESUMO
Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46%. Individuals were grouped into categories of African descent (African), Asian, Latin American, and additional/other. Across these different population groups, NS was phenotypically similar with only 2 of 21 clinical elements showing a statistically significant difference. The most common clinical characteristics found in all population groups included widely spaced eyes and low-set ears in 80% or greater of participants, short stature in more than 70%, and pulmonary stenosis in roughly half of study individuals. Using facial analysis technology, we compared 161 Caucasian, African, Asian, and Latin American individuals with NS with 161 gender and age matched controls and found that sensitivity was equal to or greater than 94% for all groups, and specificity was equal to or greater than 90%. In summary, we present consistent clinical findings from global populations with NS and additionally demonstrate how facial analysis technology can support clinicians in making accurate NS diagnoses. This work will assist in earlier detection and in increasing recognition of NS throughout the world.
Assuntos
Face/fisiopatologia , Genética Populacional , Síndrome de Noonan/genética , Povo Asiático , População Negra/genética , Criança , Feminino , Humanos , Masculino , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Síndrome de Noonan/fisiopatologia , Transdução de Sinais , População Branca/genética , Proteínas ras/genéticaRESUMO
Cardio-facio-cutaneous (CFC) syndrome is characterized by a variable degree of cognitive impairment, and multiple congenital anomalies including characteristic facies, cardiac, and ectodermal abnormalities. CFC syndrome is caused by mutations in the genes BRAF, MEK1, or MEK2. Here we provide a follow-up report on two patients presenting distinct facial appearance and other features of the syndrome, and we present the first molecular evidence of paternal origin for a CFC-causing germline mutation. Brain imaging revealed a lipoma of the corpus callosum and periventricular leukoencephalopathy as well as a hypoplastic corpus callosum, and defects in myelinization, in each patient, respectively. A review of the literature showed that, although non-specific, ventriculomegaly, hydrocephalus, and cortical atrophy represent the most frequent imaging findings of brain anomalies in CFC syndrome. CNS abnormalities are significant diagnostic features of CFC syndrome and a brain MRI is recommended in individuals diagnosed with CFC or suspected of having CFC syndrome.