True diphallia is a rare anomaly with a wide spectrum of presentation due to associated anomalies.
The wide variability of the anatomy and the presentation in diphallia cases result in different management strategies of the pathology.
Diphallia with Associated Anomalies: A Case Report and Literature Review.
Successful surgical correction of true diphallia, scrotal duplication, and associated hypospadias.
In summary, the anatomical examination of the human cadaver described above characterizes the respective case as a complete bifid penis, a subset of human diphallia, which was accompanied by proximal penoscrotal hypospadias.
Since human diphallia is an extremely rare anatomical variation as only ~ 100 cases have been reported for over 400 years, we decided to take advantage of this unique opportunity and screen for the diphallia-associated genetic variants to gain important insights into the possible cause(s) of its formation (see Supplementary Materials for experimental details).
First, it can be characterized as a complete bifid penis which accounts for one-third of all reported and extremely rare diphallia cases [1, 2].
Our results support clinical observations pointing toward human diphallia being polygenic syndrome and provide several important insights into its etiology.
Second, the mutation in KMT2C (Table 1) could indicate the involvement of the epigenetic regulatory mechanism(s) in the above process and support an early hypothesis regarding the detrimental impact of environmental factors on the fetal caudal mass of mesoderm leading to diphallia development [3].
Fourth, the proximal penoscrotal hypospadias associated with diphallia in the present case could result primarily from BMP4 mutation (Table 1) although a contribution from CYP1A1 mutation (Table S1.13) should not be ignored [27].