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.