DENND5A is a protein found in many cell types throughout the body, and thus the effects of DENND5A mutations can be widespread. However, DENND5A is most prominent in the nervous system, and thus most phenotypes are neurological. The most prevalent symptoms observed in individuals with DENND5A alterations include:
• Global developmental delay
• Seizures, which onset within the first year of life
• Enlarged ventricles in the brain
• Reduced corpus callosum volume (due to the number of fibers that connect neurons between thew two sides of the brain)
• Reduced brain volume
• Decreased and/or increased muscle tone in various parts of the body
• Small head
Approximately half of all known individuals with DENND5A variants also have problems related to breathing and digestion. These symptoms include:
• Difficulty swallowing
• Chronic constipation
• GERD
• Difficulty breathing
• Episodes of low blood oxygen content
The ability to speak and understand language are often affected, and only a minority of individuals can speak in complete sentences at a developmentally appropriate age. Gross motor skills, such as walking and sitting, and fine motor skills, such as grasping objects, are also affected.
Importantly, not all individuals with DENND5A mutations display every feature. Some present with autism spectrum disorder but show a normal brain MRI, do not have seizures, and have little to no language or motor deficits.
DENND5A