Table 3.

Genetic, clinical, and neuroimaging findings of previously reported PCH cases with genes involved in other forms of RNA-processing

PCH type/subtype	Inheritance	Genetic mutation loci	Phenotypic spectrum												References (PMID)
			Onset	Head and neck	Respiratory	Gastrointestinal	Genitourinary	Soft tissue / Skeletal	Neurologic	Behavioral / Psychiatric	Endocrine / Hematology	Paraclinical findings	biochemical findings	Others
PCH1B	AR	EXOSC3	at birth	Progressive microcephaly, Poor head control, Oculomotor apraxia, Nystagmus, Poor visual attention, Strabismus, Retinal dystrophy, Tongue atrophy, Tongue fasciculations	Respiratory insufficiency	Poor feeding	NR	Joint contractures, Hip dislocation, Foot deformities, Hypotonia, Muscle weakness, Muscle atrophy	Global developmental delay, Lack of motor milestones, Lack of speech, Spasticity, Hyperreflexia, Seizures, Axonal motor neuropathy	NR	NR	Cerebral atrophy, Cerebellar atrophy, Cerebellar cysts, Atrophy of the pons, Loss of cerebellar Purkinje cells, Loss of cerebellar granular cells, Loss of motor neurons in the spinal cord	NR	Early death may occur	11020648, 12731647, 12548734, 22544365, 23883322
PCH1C	AR	EXOSC8	in first months of life	Visual impairment, Esotropia, Nystagmus, Ophthalmoparesis, Hearing impairment, Poor head control, Dysmetria, Dysdiadochokinesia	Respiratory insufficiency, Respiratory failure	Poor feeding	NR	Severe muscle weakness, Severe muscle atrophy, Contractures, Hypotonia, mitochondrial respiratory chain (MRC) analysis showed deficiencies of complex I and III	Delayed psychomotor development, Spinal muscular atrophy, Spastic tetraparesis	NR	NR	Cerebellar vermis hypoplasia, Cerebellar atrophy, Thin corpus callosum, Cortical atrophy, Immature myelination, Loss of myelin in the cerebral and cerebellar white matter, Loss of myelin in the descending lateral spinal cord tracts	NR	Fatal in infancy, Failure to thrive	24989451, 34210538
PCH1D	AR	EXOSC9	at birth or in early infancy	Microcephaly, Poor head control, Dysmorphic facial features (Low-set ears, Nystagmus, Impaired pursuit, Poor or absent fixation, Hypertelorism, Epicanthal folds, High-arched palate, Short neck), Hypomimia	Respiratory insufficiency, Recurrent respiratory infections	Poor suckling reflex, Poor feeding, Difficulty swallowing	NR	Joint contractures, Arthrogryposis multiple congenita, Clenched fists, Adducted thumbs, Pes cavo-varus, Generalized severe hypotonia, Fasciculations, Lack of antigravity movements, Neurogenic atrophy seen on skeletal muscle biopsy	Delayed psychomotor development, Poor gross motor development, Inability to hold head, Inability to sit or walk, Absent language, Spasticity, Hyperreflexia, Seizures, Axonal motor neuronopathy, Clonus	NR	NR	Progressive cerebellar atrophy, Cerebellar hypoplasia, Cerebral atrophy, Delayed myelination, Progressive thalami atrophy	NR	Intrauterine growth retardation (IUGR), Failure to thrive, Poor overall growth, Oligohydramnios (prenatal), Decreased fetal movement, Death in childhood may occur	29727687, 30690203, 33040083, 35893425
PCH1F	AR	EXOSC1	at birth	Microcephaly, Dysmorphic facial features (Tall forehead, Long philtrum, Smooth philtrum, Retrognathia, Strabismus, Telecanthus, Blue sclerae, Depressed nasal bridge, Anteverted nares, Thick vermilion borders of the lips)	NR	NR	NR	NR	Global developmental delay, Hypotonia	NR	NR	Pontocerebellar hypoplasia, Thin corpus callosum, Cerebral atrophy, Delayed myelination, Hyporeflexia (PNS)	NR	Poor overall growth	33463720
PCH7	AR	TOE1	at birth	Progressive microcephaly, Oculomotor apraxia, Poor fixation and following, Nystagmus, Optic atrophy, Dysmorphic facial features (Micrognathia,Large ears, Epicanthal folds, Depressed nasal bridge, Broad nasal root, Prominent upper lip)	Abnormal breathing pattern, Apneic episodes	NR	Ambiguous genitalia (Male), Micropenis, Lack of gonadal tissue (Male), Testicular regression	Hypotonia, dystonia	NR	Severe delayed psychomotor development, Developmental delay, Seizures, Moderate intellectual disability, Poor or absent speech, Poor spontaneous movements, Spastic paraplegia, Hyperreflexia, Myoclonus	Increased baseline gonadotropins, Functional anorchia	Pontocerebellar hypoplasia, Cerebral atrophy, Thin corpus callosum, Rudimentary white matter, Lack of ependymal cells, Cerebellar neuronal loss	NR	NR	11068172, 21594990, 23686794, 28092684, 36738896, 34716526
PCH14	AR	PPIL1	at birth	Progressive microcephaly	NR	NR	NR	NR	NR	Poor or absent psychomotor development, Impaired intellectual development, Absent language, Absent social skills, Hypotonia, Spastic quadriplegia, Brisk reflexes, Dystonia, Seizures	NR	Pontocerebellar hypoplasia, Agenesis of the corpus callosum, Myelination defects, Simplified gyral pattern, Brainstem hypoplasia	NR	Early death may occure	33220177
PCH15	AR	PRP17 (CDC40)	at birth	Progressive microcephaly	NR	NR	NR	NR	NR	Poor or absent psychomotor development, Impaired intellectual development, Absent language, Absent social skills, Hypertonia, Spastic quadriplegia, Brisk reflexes, Seizures	Anemia, Thrombocytopenia	Pontocerebellar hypoplasia, Partial agenesis of the corpus callosum, Brainstem hypoplasia	NR	NR	33220177