Table 3. [Genes of Interest in the Differential Diagnosis of PI4KA-Related Disorder]. - GeneReviews®

Gene	DiffDx Disorder	MOI	Key Features of DiffDx Disorder
HYCC1 (FAM126A)	Hypomyelination & congenital cataract	AR	Hypomyelinating leukodystrophy. Cerebellar signs are variably present.	Congenital cataracts variably present & psychomotor regression; peripheral neuropathy present in majority of affected persons. Polymicrogyria, IBD, & immunodeficiency have not been described.
PLP1	PLP1 disorders incl Pelizaeus-Merzbacher disease & spastic paraplegia 2 (SPG2)	XL	Hypomyelinating leukodystrophy. Prominent cerebellar features. Variable age of onset w/spastic paraparesis described as SPG2 in those w/later onset.	Polymicrogyria, IBD, & immunodeficiency have not been described.
RARS1	RARS1-related hypomyelinating leukodystrophy (OMIM 616140)	AR	Hypomyelinating leukodystrophy. Severe refractory epilepsy / epileptic encephalopathy has been described.	Polymicrogyria, IBD & immunodeficiency have not been described.
TTC7A	Gastrointestinal defects & immunodeficiency syndrome (OMIM 243150)	AR	Heterogeneous intestinal & immunologic disease manifestations incl but not limited to multiple intestinal atresia, very early-onset IBD, & combined immunodeficiency	Neurologic anomalies have not been described.

Gene

DiffDx Disorder

MOI

Key Features of DiffDx Disorder

Overlapping w/PI4KA-related disorder

Distinguishing from PI4KA-related disorder

HYCC1 (FAM126A)

Hypomyelination & congenital cataract

Hypomyelinating leukodystrophy. Cerebellar signs are variably present.

Congenital cataracts variably present & psychomotor regression; peripheral neuropathy present in majority of affected persons. Polymicrogyria, IBD, & immunodeficiency have not been described.

PLP1

PLP1 disorders incl Pelizaeus-Merzbacher disease & spastic paraplegia 2 (SPG2)

Hypomyelinating leukodystrophy. Prominent cerebellar features. Variable age of onset w/spastic paraparesis described as SPG2 in those w/later onset.

Polymicrogyria, IBD, & immunodeficiency have not been described.

RARS1

RARS1-related hypomyelinating leukodystrophy (OMIM 616140)

Hypomyelinating leukodystrophy. Severe refractory epilepsy / epileptic encephalopathy has been described.

Polymicrogyria, IBD & immunodeficiency have not been described.

TTC7A

Gastrointestinal defects & immunodeficiency syndrome (OMIM 243150)

Heterogeneous intestinal & immunologic disease manifestations incl but not limited to multiple intestinal atresia, very early-onset IBD, & combined immunodeficiency

Neurologic anomalies have not been described.

From: PI4KA-Related Disorder

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Adam MP, Feldman J, Mirzaa GM, et al., editors.

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