Gene - HIVEP2

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Research Article Summaries: 

Below, we've summarized several research articles that include information about HIVEP2. We hope you find this information helpful! As we learn more from children who have these gene changes, we expect this list of resources and information to grow.

  • Steinfeld et al., 2016 - Mutations in HIVEP2 are associated with developmental delay, intellectual disability, and dysmorphic features

This article takes a look at how deleterious (damaging) changes in the HIVEP2 gene may affect individuals. In the published literature, previous studies of HIVEP2 genetic changes have documented intellectual disability and developmental delay in three patients. This study further examines the behavioral, medical, and developmental features of six patients who have genetic changes in HIVEP2.

After complete medical evaluation, including whole exome sequencing (WES), MRI, and physical examination, the following features were documented:

  • All six patients had developmental delay, intellectual disability, and mild dysmorphic features.
  • Autism, hyperactivity, anxiety, and oppositional behaviors were common behavioral issues.
  • Two of the children (ages 10 and 14yrs) were nonverbal and one child (age 2) spoke only three words. One child (age 11) spoke in full sentences and another child (age 6) spoke only 3 to 4 word sentences.
  • IQ ranged from 50 to 75.
  • Two of the children experienced seizures.
  • Four of the six children have hypotonia (decreased muscle tone) and one child has hypertonia (increased muscle tone on arms and legs).
  • Three of the children had microcephaly (decreased brain and head size).
  • Gastrointestinal issues of constipation and gastroesophogeal reflux disease were reported.
  • Opthalmologic issues, including strabismus (visual condition in which eyes do not point in the same direction) and amblyopia (“lazy eye”) were reported in three of the children.

Overall, the common features that have been seen in all nine patients (6 from this study and 3 from the literature) are hypotonia, developmental delay, intellectual disability, and dysmorphic features, providing further evidence of the association between these features and genetic changes inHIVEP2


  • Srivastava et al., 2015 – Loss-of-function variants in HIVEP2 are a cause of intellectual disability

    Using whole exome sequencing, this study identified three individuals with new (de novo) variants in the HIVEP2 gene. The HVIEP2 gene is linked to a protein in the brain. This protein regulates other genes, many of which are related to brain growth and development. All three individuals exhibited varying degrees of global developmental delay and intellectual disability, brain abnormalities, and in two cases, behavioral issues. All three also had various abnormal physical features. While not currently linked to one diagnosis, the relationship between HIVEP2 and the brain suggests that these de novo variants may be causative of the clinical features observed in the individuals in this study.