Pontocerebellar hypoplasia type 6

General Information (adopted from Orphanet):

Synonyms, Signs: PCH6
Fatal infantile encephalopathy with mitochondrial respiratory chain defects
Encephalopathy, fatal infantile, with mitochondrial respiratory chain defects
Number of Symptoms 37
OrphanetNr: 166073
OMIM Id: 611523
ICD-10: Q04.3
UMLs: C1969084
MeSH: C548074
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: < 10 cases [Orphanet]
Inheritance: Autosomal recessive
20635367 [IBIS]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Mitochondrial disorder due to a defect in mitochondrial protein synthesis
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease
Nonsyndromic pontocerebellar hypoplasia
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Mutations in the mitochondrial arginyl tRNA synthetase (RARS2 = ArgRS, DALRD2, PCH6, PRO1992, RARSL) gene are associated with Pontocerebellar Hypoplasia type 6 (PCH6) (PMID:20635367).

Symptom Information: Sort by abundance 

1
 (HPO:0008872) Feeding difficulties in infancy 20635367 IBIS 153 / 7739
2
 (HPO:0011470) Nasogastric tube feeding in infancy 20635367 IBIS 1 / 7739
3
 (HPO:0002033) Poor suck 20635367 IBIS 37 / 7739
4
 (HPO:0000490) Deeply set eye 20635367 IBIS 131 / 7739
5
 (HPO:0002151) Increased serum lactate 20635367 IBIS 92 / 7739
6
 (HPO:0001508) Failure to thrive 20635367 IBIS 454 / 7739
7
 (HPO:0008972) Decreased activity of mitochondrial respiratory chain 20635367 IBIS 34 / 7739
8
 (HPO:0011923) Decreased activity of mitochondrial complex I 20635367 IBIS 35 / 7739
9
 (HPO:0011924) Decreased activity of mitochondrial complex III 20635367 IBIS 22 / 7739
10
 (HPO:0008347) Decreased activity of mitochondrial complex IV 20635367 IBIS 31 / 7739
11
 (HPO:0200125) Mitochondrial respiratory chain defects 20635367 IBIS 6 / 7739
12
 (HPO:0000969) Edema 20635367 IBIS 117 / 7739
13
 (HPO:0001252) Muscular hypotonia 20635367 IBIS 990 / 7739
14
 (HPO:0008947) Infantile muscular hypotonia 20635367 IBIS 482 / 7739
15
 (HPO:0002421) Poor head control 20635367 IBIS 23 / 7739
16
 (HPO:0002490) Increased CSF lactate 20635367 IBIS 28 / 7739
17
 (HPO:0001348) Brisk reflexes 20635367 IBIS 15 / 7739
18
 (HPO:0001257) Spasticity 20635367 IBIS 251 / 7739
19
 (HPO:0002061) Lower limb spasticity 20635367 IBIS 56 / 7739
20
 (HPO:0006986) Upper limb spasticity 20635367 IBIS 15 / 7739
21
 (HPO:0001263) Global developmental delay 20635367 IBIS 853 / 7739
22
 (HPO:0001250) Seizures 20635367 IBIS 1245 / 7739
23
 (HPO:0000252) Microcephaly 20635367 IBIS 832 / 7739
24
 (HPO:0001999) Abnormal facial shape 20635367 IBIS 169 / 7739
25
 (HPO:0000189) Narrow palate 20635367 IBIS 45 / 7739
26
 (HPO:0000426) Prominent nasal bridge 20635367 IBIS 121 / 7739
27
 (HPO:0002104) Apnea 20635367 IBIS 106 / 7739
28
 (HPO:0007366) Atrophy/Degeneration affecting the brainstem 20635367 IBIS 4 / 7739
29
 (HPO:0001272) Cerebellar atrophy 20635367 IBIS 197 / 7739
30
 (HPO:0001321) Cerebellar hypoplasia Very frequent [IBIS] 20635367 IBIS 114 / 7739
31
 (HPO:0001320) Cerebellar vermis hypoplasia 20635367 IBIS 57 / 7739
32
 (HPO:0002059) Cerebral atrophy 20635367 IBIS 171 / 7739
33
 (HPO:0003819) Death in childhood 20635367 IBIS 42 / 7739
34
 (HPO:0001522) Death in infancy 20635367 IBIS 275 / 7739
35
 (HPO:0003676) Progressive disorder 20635367 IBIS 148 / 7739
36
 (OMIM) Edematous hands and feet (1 patient) 20635367 IBIS 1 / 7739
37
 (OMIM) Limb spasticity 20635367 IBIS 3 / 7739

Associated genes:

RARS2;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Pontocerebellar hypoplasia (PCH) is a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem and associated with severe developmental delay (Edvardson et al., 2007).

For a phenotypic description and a discussion of genetic ...
Clinical Description OMIM Edvardson et al. (2007) investigated 3 patients, the products of a consanguineous Sephardic Jewish marriage, who had infantile encephalopathy and a putative defect in mitochondrial translation. The eldest of the 3 affected children showed generalized hypotonia and poor ...
Molecular genetics OMIM Because defects in mitochondrial respiratory chain complexes in affected patients suggested a defect in synthesis of mtDNA-encoded proteins, Edvardson et al. (2007) sequenced the RARS2 gene, which they identified in the region on chromosome 6q16.1 linked to the ...