Congenital nephrotic syndrome (CNS) is usually caused by genetic defects affecting the glomerular filter. The most common defects are nephrin mutations whereas defective
WT1,
PLCE1,
LAMB2, or
NPHS2 gene products are less common [
1,
2]. Additionally, CNS has been described in association with metabolic diseases, such as respiratory chain deficiency [
3]. Variants in integrin α3 (ITGA3) are known to cause lung disease in combination with nephrotic syndrome [
4]. The most common non-genetic causes are infectious diseases, such as cytomegalovirus infection [
5,
6] and congenital syphilis [
7].
CNS can also occur in congenital disorders of glycosylation (CDG). So far, it has been described in the subtypes PMM2-CDG, ALG1-CDG, and various cases of CDG-x, i.e., cases in which the subtype has not been identified.
Taking the dysmorphic and multiorgan presentation of the described patient into account, the differential diagnosis in the presented case consists of mitochondrial cytopathy, CDG, and ITGA3 disease. The most likely option with regards to the typical dysmorphic presentation, i.e., inverted nipples and facial dysmorphisms, is CDG.