Clinical Characteristics

Pregnancy and neonatal course
Pregnancy is typically uneventful; one patient presented with mild intra-uterine growth retardation (IUGR). Early feeding difficulties are frequent during the neonatal period.

Core clinical features
The four core clinical features of the O2HE syndrome described in the first patients include:

  • Congenital diarrhea due to microvilli atrophy, of various severity
  • Cholestasis causing chronic pruritus
  • Perception deafness and
  • Bone fragility

Learning disability not completely explained by the hearing impairment and/or intellectual disability of various degree seem associated to the clinical features, and collecting new cases will be of importance for answering that question.

Other features
The clinical spectrum may be enlarged to the presence of malformations, since one unreported patient presented with left anophthalmia and right iris coloboma, and another one with cleft palate. With unique malformations, we cannot be sure that they are caused by biallelic variants of UNC45A. There is no apparently distinctive facial feature in the first published patients.