Table 3 Genetic, clinical, and neuroimaging findings of previously reported PCH cases with genes involved in other forms of RNA-processing

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