Xq22.3q23 microdeletion harboring TMEM164 and AMMECR1 genes: Two case reports confirming a recognizable phenotype with short stature,midface hypoplasia,intellectual delay,and elliptocytosis

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.     

Left pulmonary artery sling associated with right pulmonary hypoplasia and ventricular septal defect

The pulmonary artery sling is a congenital malformation where the left pulmonary artery forms a vascular sling that bends around the right border of the lower trachea. Its clinical manifestations are signs of tracheal compression in the first months of life. The diagnosis of this rare anomaly is suspected on radiological and echocardiographic grounds and confirmed by oesophagography, tracheoscopy and angiocardiography. Diagnostic problems may be encountered when the condition is associated with tracheobronchial (50% of the cases) or cardiovascular malformations. In the case reported here respiratory symptoms and heart failure were present in a 1-month hypotrophic infant who also had ventricular septal defect and dextrocardia due to right lung hypoplasia. The pulmonary artery sling was diagnosed by angiography. The severity of the clinical signs precluded all attempts at surgical repair of the cardiovascular anomalies. The child died at the age of 2 1/2 months.     

Split hand/foot malformation with long‐bone deficiency and BHLHA9 duplication: report of 13 new families

Split hand/foot malformation (SHFM) with long‐bone deficiency (SHFLD, MIM#119100) is a rare condition characterized by SHFM associated with long‐bone malformation usually involving the tibia. Previous published data reported several unrelated patients with 17p13.3 duplication and SHFLD. Recently, the minimal critical region had been reduced, suggesting that BHLHA9 copy number gains are associated with this limb defect. Here, we report on 13 new families presenting with ectrodactyly and harboring a BHLHA9 duplication.     

Prenatal diagnosis of mucoviscidosis: indication of enzyme determination and molecular biology techniques]

Prenatal diagnosis of cystic fibrosis established by study of RFLPs flanking the gene and, since 1989, by direct detection of the major mutation delta F508 is now widely used. However, there are still some indications of prenatal diagnosis by microvillar intestinal enzymes analysis. We propose a prenatal diagnosis strategy which combines both methods. This diagnosis strategy is applied to families with a 1/4 to 1/200 risk. Screening of delta F508 in the general population is discussed.     

Bourneville's tuberous sclerosis of neonatal disclosure. Apropos of 2 cases

A cardiac murmur was found in a newborn, after 12 hours of life. It was related to an intracardiac tumor, and we made the diagnosis of tuberous sclerosis. The same diagnosis was made in another patient, with a tumor diagnosed by obstetrical echography. In these two cases, seizures occurred rapidly during the evolution. In one case, the heredity was dominant, in the other one, it was a "de novo" mutation. It is unusual to diagnose tuberous sclerosis during the neonatal period, so we report these two cases.     

Diagnosis and treatment of fetal tachycardia. Apropos of 2 cases

Fetal echocardiographic studies were performed in 2 patients referred for evaluation of cardiac dysrythmias. Supra-ventricular tachycardia were diagnosed in the 2 patients. Appropriate prenatal treatment can not avoid premature deliveries in one case. Evaluation of in utero cardiac arrhythmias and monitoring of in utero therapy are discussed.