RESUMO
The AMME syndrome defined as the combination of Alport syndrome, intellectual disability, midface hypoplasia, and elliptocytosis (AMME) is known to be a contiguous gene syndrome associated with microdeletions in the region Xq22.3q23. Recently, using exome sequencing, missense pathogenic variants in AMMECR1 have been associated with intellectual disability, midface hypoplasia, and elliptocytosis. In these cases, AMMECR1 gene appears to be responsible for most of the clinical features of the AMME syndrome except for Alport syndrome. In this article, we present two unrelated male patients with short stature, mild intellectual disability or neurodevelopmental delay, sensorineural hearing loss, and elliptocytosis harboring small microdeletions identified by array-CGH involving TMEM164 and AMMECR1 genes and SNORD96B small nucleolar RNA for one patient, inherited from their mothers. These original cases further confirm that most specific AMME features are ascribed to AMMECR1 haploinsufficiency. These cases reporting the smallest microdeletions encompassing AMMECR1 gene provide new evidence for involvement of AMMECR1 in the AMME phenotype and permit to discuss a phenotype related to AMMECR1 haploinsufficiency: developmental delay/intellectual deficiency, midface hypoplasia, midline defect, deafness, and short stature.
Assuntos
Deleção Cromossômica , Cromossomos Humanos X/genética , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/patologia , Eliptocitose Hereditária/genética , Eliptocitose Hereditária/patologia , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Proteínas de Membrana/genética , Nefrite Hereditária/genética , Nefrite Hereditária/patologia , Proteínas/genética , Criança , Humanos , Masculino , PrognósticoRESUMO
Noonan syndrome is a well-known genetic condition associating congenital heart defects, short stature, and distinctive facial features. Pulmonary valve stenosis and hypertrophic cardiomyopathy are the most frequent cardiac abnormalities, the latter being associated with a higher mortality. Here we report for the first time, a case of congenital left main coronary artery atresia in a Noonan syndrome associated with RIT1 variant, leading to unrescued sudden death. This case-report supports the already-suspected severity of the RIT1-related Noonan syndrome compared to average Noonan syndrome, and should encourage clinicians to be very cautious with these patients.