Families

Clinical features
Individuals with PI4KA-associated disorders can have a variable clinical picture, ranging from a neurodevelopmental disorder with onset at birth associated with severe brain developmental abnormalities to motor difficulties caused by lower limb rigidity beginning in adolescence.
In addition, affected individuals may present with inflammatory bowel disease, multiple intestinal atresia (closure of a natural passage) and combined immunodeficiency and/or abnormalities of the genitourinary system.

Prevalence
PI4KA-associated disorders are extremely rare, with only 19 families reported to date.

Inheritance
The disease is inherited in an autosomal recessive manner: this means that both copies of the PI4KA gene must be mutated in an individual to be affected, whereas heterozygotes (with only one mutated copy) are asymptomatic carriers and thus do not manifest the condition but are at risk of transmitting it. Parents of a patient are usually carriers of the mutations and they have a 25% chance to have other children affected. Therefore, a genetic counselling and testing at risk family members are crucial for these families.