Urofacial syndrome is genetically heterogeneous.
Biallelic variants in HPSE2 have been identified in the majority of all cases reported with urofacial syndrome.
Loss of function pathogenic variants (nonsense, deletions and frameshift) result in the phenotype. To date, there is a single report of a homozygous missense variant resulting in urofacial syndrome.
The loss of heparanase 2 results in a peripheral neuropathy affecting the autonomic nervous system.
Diagnostic testing is available as a single gene, as part of panels associated with bladder dysfunction or through exome or genome sequencing analysis.
There are no functional assays of the effects of variants in HPSE2.
HPSE2