Table 3.

Cases of neurodevelopmental delay in inborn errors of immunity/monogenic deficiencies associated with disturbed class 1A PI3K signaling.

Disease	OMIM#	Gene	Inheritance	PI3K signaling	Immunological defect	Neurodevelopmental delay	References
APDS1	615513	PIK3CD	AD	Increased	Ig serum level, B and T	19% of patients in cohort study;global development, speech delay, autism spectrum disorder	(5, 25)
APDS2	616005	PIK3R1	AD	Increased	Ig serum level, B and T	31% of patients in cohort study; cognitive impairments, learning disabilities	(4)
SHORT syndrome	269880	PIK3R1	AD	Decreased	N.R.	Behavioral problemsspeech delay	(26, 27)
p85α deficiency	615214	PIK3R1	AR	N.R.	B absent, Ig serum level,	N.R.	(23)
P110delta deficiency		PIK3CD	AR	Decreased	B and NK decreased, T impaired Ig serum level,	N.R.	(20, 22, 24)
Roifman–Chitayat syndrome	613328	PIK3CD/KNSTRN	AR		Ig serum level, B and NK decreased, T impaired	Developmental delay; cognitive, speech, and motor retardation,tremor, ataxia	(19)
APDS-L/Cowden syndrome1/macrocephaly/autism syndrome	158350/605309	PTEN	AD	Increased	Ig serum level, B and T	Autism spectrum disorders; developmental delay and macrocephaly	(28–32)

NK, natural killer; N.R., not reported.