Comparing patient one and patient two
Both our patients had many of the characteristic features reported in SYS such as short stature, dysmorphic facial features, hypogonadism, arthrogryposis multiplex congenital (AMC), hypotonia, respiratory depression with apneic episodes, feeding difficulties requiring g-tube placement, and delayed psychomotor development3,16(Table 2. Comparative table of clinical features presented by Patient 1 and Patient 2). Nonetheless, there were some notable differences between both patients. Patient 1 had IUGR and a birth weight in the 5th percentile while Patient 2 had a birth weight in the 75th percentile. Patient 1 is tracheostomy dependent and had more severe congenital contractures while patient 2 only required invasive respiratory support for a short period and had milder contractures primarily involving the hands. Patient 1 also had unexplained hypernatremia and persistent hypoglycemia. However, it is unknown whether these endocrine abnormalities were associated to the MAGEL2 variant or whether the ABCC8 variant, found as an incidental finding, may have contributed to these clinical features.
MacArthy et al. 2018, reported an association between the phenotypic severity and the location of the truncating mutation and, described a genotype-phenotype association comparing individuals with the p.Gln666ProfsTer47 MAGEL2 variant with other mutations. According to their prediction, this variant can be associated with severe phenotypes, including a higher prevalence of joint contractures; more severe feeding difficulties likely to require a nasogastric feeding tube; more severe respiratory difficulties likely to require mechanical ventilation and; more likely to have profound intellectual disability/significant developmental delay.3 Both patient 1 and patient 2 carry the p.Gln666ProfsTer47 variant inMAGEL2 . Both had congenital contractures, required NG/G-tube placement, invasive respiratory support, and had significant developmental delays supporting the phenotype-genotype association described by MacArthy et al. 2018.
It is important to note that hypopituitarism is reported as typically present in patients with SYS but neither of the two patients have presented with it. Likewise, hyperphagia has been reported to be present in 22% of reported cases3 and, although patient 2 has been noted to be overweight, it is unclear if hyperphagia is present or not.