Table 2 Genetic, clinical, and neuroimaging findings of previously reported PCH cases with genes involved in tRNA-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 Manifestations | Endocrine | Paraclinical findings | biochemical | Others | ||||
PCH2A | AR | TSEN54 | at birth | Progressive microcephaly, central visual impairment, abnormal visual pursuit | NR | Poor feeding, Poor sucking | NR | Hypertonia at birth | Profound developmental delay, Restlessness at birth, Inability to sit or control head, Extrapyramidal dyskinesia, Spasticity, Opisthotonus, Seizures | NR | NR | Cerebellar hypoplasia, Pontine hypoplasia, 'Dragonfly-like' pattern, Cortical atrophy, Loss of Purkinje cells, Periventricular white matter abnormalities, Diffuse cerebral gliosis, Absence of transverse pontine fibers | NR | Death in childhood may occur | 7854532, 20956791, 20952379 |
PCH2B | AR | TSEN2 | at birth | Progressive microcephaly, Sloping forehead, Central visual impairment, Lack of visual fixation | NR | Feeding difficulties | NR | Hypotonia | No psychomotor development, Dyskinesias, Dystonia, Clonus, Spasticity, Opisthotonus, Chorea, Axial hypotonia, Limb hypertonia, Extensor plantar responses, Seizures | NR | NR | Cerebellar atrophy, Brainstem hypoplasia, Pontine atrophy, 'Dragonfly' pattern on imaging, Thin corpus callosum, Cerebral atrophy, Ventricular dilatation, Simplified gyral pattern | NR | Death in early childhood may occur | 23562994, 20952379 |
PCH2C | AR | TSEN34 | NR | Central visual impairment | NR | NR | NR | NR | Epileptic seizures | NR | NR | mild involvement of cerebellum and pons | NR | NR | 20952379 |
PCH2D | AR | SEPSECS | in infancy | Progessive microcephly, ocular nystagmus, head titubation, bilateral optic nerve hypoplasia, visual impairment | progressive chronic respiratory insufficiency | Poor sucking | NR | Contractures in limbs, abolished DTR, Hypotonia | Mental retardation, Lack of psychomotor development, Progressive spastic quadriplegia, Ataxia, Clonus, Seizures, Mild chorea, Sleep disturbances, Bradykinesia, extrapyramidal rigidity, cerebellar syndrome (scanning speech and appendicular dysmetria, with ataxic gait and inability to walk in tandem), pyramidal tract involvement (exaggerated deep tendon reflexes and absent plantar reflex bilaterally) | Irritability | NR | Progressive cerebellar atrophy (cerebellar vermal atrophy before cerebral atrophy), Progressive cerebral atrophy, Delayed myelination, Decreased white matter volume, Thin corpus callosum, Periventricular white matter abnormalities | NR | Reduction in mitochondrial complex I and II activity and an increased number a of type 1 fibers in the muscle (35091508) | 25044680, 12920088, 35252561, 35091508, 35637137, 36085396, 29464431, 26888482 |
PCH2F | AR | TSEN15 | at birth | Progressive microcephaly, Strabismus, Poor or absent eye fixation | NR | NR | NR | Hypotonia | Intellectual disability, Motor delay, Inability to walk, Poor or absent speech, Seizures, Spasticity, Hyperreflexia, Extensor plantar responses | NR | NR | Pontocerebellar hypoplasia, Cortical atrophy | NR | NR | 25558065, 27392077 |
PCH4 | AR | TSEN54 | at birth | Microcephaly | Little spontaneous breath, Central respiratory failure | Swallowing disturbances | NR | Hypertonia at birth, Congenital contractures | Profound delayed psychomotor development, Seizures, Spasticity, Myoclonus | NR | NR | Cerebellar hypoplasia, Decreased cerebellar folia, Cerebellar cortex shows normal layers, Loss of Purkinje cells, Pontine hypoplasia, Brainstem hypoplasia, Shrunken inferior olivary nuclei, Neocortical atrophy | NR | Polyhydramnios (prenatal), Death usually in infancy | 8480512, 20956791, 20952379, 18711368 |
PCH5 | AR | TSEN54 | in utero | Microcephaly | NR | NR | NR | Congenital contractures | Seizure | NR | NR | Dysplastic C-shaped inferior olivary nuclei, Absent or immature dentate nuclei, Cerebellar cell paucity (more marked in vermis than hemispheres), Cerebellar hypoplasia, Severe olivopontocerebellar hypoplasia | NR | Polyhydramnios (prenatal), Death in neonatal period | 16470708 |
PCH6 | AR | RARS2 | at birth | Progressive microcephaly, Dysmorphic features (Bitemporal narrowing, Deep-set eyes, Prominent nasal bridge, Narrow mouth palate), Vision loss, Dysconjugate eye movements | Apneic episodes | Poor sucking, Feeding difficulties | NR | Hypotonia, Edematous hands and feet, Contrature, Reduced activity of mitochondrial respiratory chains | Profound developmental delay, Lack of speech, Poor head control, Seizures, Limb spasticity, Spastic quadriplegia, Clonus, Hyperreflexia | NR | NR | Cerebral atrophy, Cerebellar atrophy, Brainstem atrophy | Increased serum lactate, Increased CSF lactate | Failure to thrive, Death in childhood | 20952379, 17847012, 20635367, 25809939, 34717047, 35707589 |
PCH10 | AR | CLP1 | at birth | Progressive microcephaly, Dysmorphic features (Prominent eyes, Long palpebral fissures, High-arched eyebrows, Long eyelashes, Poor eye contact, Esotropia, Strabismus, Nystagmus, Broad nasal root, Hypoplastic alae nasi, Short nose, High-arched palate, Thin upper lip) | NR | NR | Cryptorchidism | Kyphoscoliosis, Hip abnormalities | Profound delayed psychomotor development, Encephalopathy, Lack of independent sitting or walking, Seizures, intractable, Lack of speech, Hypertonia, Spasticity, Hyperreflexia, Axonal sensorimotor neuropathy | NR | NR | Thin corpus callosum, Pontocerebellar hypoplasia, Cortical dysgenesis, Simplified gyral pattern, Cortical atrophy, White matter abnormalities, Enlarged ventricles, Delayed myelination | NR | Poor growth | 24766809, 24766810, 29307788 |