Table 1:

Overview of common clinical findings in diseases arising from variants in genes encoding Pol III subunits.

	POLR3-related leukodystrophy	Ataxia, spasticity and demyelinating neuropathy	Wiedemann-Rautenstrauch syndrome	Endosteal hyperostosis	Isolated Hypogonadotropic Hypogonadism
Pol III subunit affected	POLR3A, POLR3B, POLR1C, POLR3K	POLR3B	POLR3A, POLR3B, POLR3GL	POLR3GL	POLR3B
Inheritance	Autosomal recessive	De novo	Autosomal recessive	Autosomal recessive	Autosomal recessive
Neurological features	Cerebellar (ataxia, dysmetria, dysarthria), Pyramidal (spasticity), Extrapyramidal (dystonia) signs, Cognitive involvement	Pyramidal (spasticity), Cerebellar signs (ataxia, dysmetria, dysarthria) Sensorimotor demyelinating peripheral neuropathy Developmental delay, Epilepsy	Not common – Hypotonia and/or Developmental delay in some individuals	Motor delay, Hypotonia, Mild intellectual disability	-
Myelin	Diffuse brain hypomyelination	Peripheral nerves demyelination	-	-	-
Teeth	Hypodontia, Oligodontia, Delayed dentition, Natal teeth, etc.	-	Oligodontia, Natal teeth	Oligodontia	-
Endocrine	Hypogonadotropic hypogonadism (absent, delayed or arrested puberty), growth hormone deficiency, others	-	-	Hypogonadotropic Hypogonadism	Hypogonadotropic Hypogonadism
Growth	Short stature	-	Short stature	Short stature	-
Eyes	Myopia	-	Myopia, Hyperopia or normal vision	Hyperopia	-
Bone	Osteosclerosis (rare), Endosteal Sclerosis in some patients with biallelic POLR3B variants	-	Congenital fractures	Axial endosteal hyperostosis	-
Adipose tissue	-	-	Lipodystrophy, Abnormal distribution of fat tissue	-	-
Craniofacial bones	Not common - reported in some patients with biallelic POLR1C variants	-	Characteristic facial features ex. triangular face, widened fontanelles, mandibular hypoplasia	Dysmorphic facial features	-