Most individuals with DBS, which is always caused by biallelic LRP2 mutations, have these characteristics:
Craniofacial features
- macrocephaly at birth
- broad forehead and frontal bossing
- hypertelorism
- prominent brows
- downward palpebral slant
- flat nasal bridge
- short nose with indented tip
- low-set and posterior angulated ears
Eyes and vision
- enlarged globes
- progression to high grade myopia (-20 diopters bilaterally)
- significantly increased risk of retinal detachment
- iris hypoplasia and coloboma
- subcapsular opacities and cataracts
Ears and hearing
- progression to bilateral moderate or profound sensorineural hearing loss (SNHL)
Central nervous system
- agenesis of the corpus callosum (ACC)
Kidney
- low-molecular-weight proteinuria (LMWP)
- reduced tubular uptake of LRP2 ligands
Other structural congenital anomalies
- congenital diaphragmatic hernia (CDH)
- omphalocele
Less commonly reported findings are:
Eyes
- leukocoria and retinal dystrophy
- exotropia
- vitreous anomalies
Kidney
- nephrocalcinosis and nephrolithiasis
- microalbuminuria
- progression to renal dysfunction
Brain/Central nervous system
- developmental delay
- seizures
Other structural congenital anomalies
- umbilical hernia
- wide metopic suture
- congenital heart disease (e.g. ventricular septal defect, double-outlet right ventricle)
- urogenital anomalies