The combination of a severe pathogenic variant (predicting stop codons or structural variants in transmembrane domains) with a pathogenic variant located in extracellular loops, in the cytoplasmic tail of the protein, or in the regulatory 5'-flanking region of the gene results in the less severe phenotypes, i.e., AO2 and DTD. Spinal scoliosis and dislocation of the elbows are reported. Epicanthal folds, widely spaced eyes, and low-set ears can also be present. Midface retrusion is usually present, together with a flat nasal bridge and micrognathia.
Cleft palate is a constant feature, whereas the degree of facial dysmorphism is variable. The neck is short, the thorax narrow, and the abdomen protuberant.Ĭraniofacial features. Disproportion between the short skeleton and normal-sized skull is immediately evident the limb shortening is mainly rhizomelic the gap between the toes, ulnar deviation of the fingers, and adducted thumbs are typical of sulfate transporter-related dysplasias. AO2 is clinically very similar to diastrophic dysplasia (DTD). Newborns with AO2 present with short limbs, adducted feet with wide space between the hallux and the second toe, hitchhiker thumb, cleft palate, and facial dysmorphism. Pregnancy complication of polyhydramnios may occur. The dysmorphic facial features are very consistent and cleft palate is frequent.ĪO2 is usually lethal in the neonatal period because of lung hypoplasia, tracheobronchomalacia, and laryngeal malformations. Almost all individuals will have club feet (adducted feet) and many will have lung hypoplasia (consequences of the generalized skeletal alterations). It follows, then, that the diagnosis of AO2 will only apply to a fetus/individual with severe prenatal-onset short stature. The diagnosis of AO2 should be made only if the specific SLC26A2 pathogenic variants have already been described in an individual with AO2 and/or the clinical and radiographic severity lies somewhere between achondrogenesis 1B and diastrophic dysplasia (see Genetically Related Disorders). The following description of the phenotypic features associated with this condition is based on these reports. To date, only a handful of individuals with atelosteogenesis type 2 (AO2) have been reported with biallelic pathogenic variants in SLC26A2.
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