Alternative titles; symbols
SNOMEDCT: 718607001; ORPHA: 166068; DO: 0060274;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17q25.1 | ?Pontocerebellar hypoplasia type 5 | 610204 | Autosomal recessive | 3 | TSEN54 | 608755 |
A number sign (#) is used with this entry because of evidence that pontocerebellar hypoplasia type 5 (PCH5) is caused by compound heterozygous mutation in the TSEN54 gene (608755) on chromosome 17q25. One such patient has been reported.
Pontocerebellar hypoplasia (PCH) refers to a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem (summary by Patel et al., 2006).
For a phenotypic description and a discussion of genetic heterogeneity of pontocerebellar hypoplasia, see PCH1 (607596).
Patel et al. (2006) described 3 sibs, born of nonconsanguineous parents, with a precise onset of fetal seizure-like activity who had severe olivopontocerebellar hypoplasia (OPCH) and degeneration. Autopsies at 20, 27, and 37 weeks' gestation showed diffuse central nervous system volume loss that was most marked for the cerebellum and brainstem structures. Neuropathologic abnormalities included dysplastic, C-shaped inferior olivary nuclei, absent or immature dentate nuclei, and cell paucity more marked for the cerebellar vermis than the hemispheres. Delayed development was seen in layer 2 of the cerebral cortex and in Purkinje cells of the cerebellum. Prenatal monitoring defined a developmental window of 16 to 18 weeks' gestation when ultrasonic assessment of cerebellar width was used for prenatal diagnosis. Family history was significant for a healthy older sister and a healthy younger brother, as well as a miscarriage at 12 weeks' gestation. Patel et al. (2006) designated this disorder pontocerebellar hypoplasia type 5.
The transmission pattern of PCH5 in the family reported by Patel et al. (2006) was consistent with autosomal recessive inheritance.
In 1 of the sibs with PCH5 reported by Patel et al. (2006), Namavar et al. (2011) identified compound heterozygous mutations in the TSEN54 gene: 1 allele carried a common A307S mutation (608755.0001) found in patients with the milder phenotype PCH2A (277470), and the other allele carried a putative splice site mutation (608755.0006). Functional studies of the variants were not performed. Namavar et al. (2011) noted the phenotypic similarity to PCH4 (225753), which is caused by compound heterozygosity for A307S and different pathogenic TSEN54 mutations. The findings indicated that biallelic TSEN54 mutations can cause a spectrum of clinical manifestations of PCH.
Namavar, Y., Chitayat, D., Barth, P. G., van Ruissen, F., de Wissel, M. B., Poll-The, B. T., Silver, R., Baas, F. TSEN54 mutations cause pontocerebellar hypoplasia type 5. Europ. J. Hum. Genet. 19: 724-726, 2011. [PubMed: 21368912] [Full Text: https://doi.org/10.1038/ejhg.2011.8]
Patel, M. S., Becker, L. E., Toi, A., Armstrong, D. L., Chitayat, D. Severe, fetal-onset form of olivopontocerebellar hypoplasia in three sibs: PCH type 5? Am. J. Med. Genet. 140A: 594-603, 2006. [PubMed: 16470708] [Full Text: https://doi.org/10.1002/ajmg.a.31095]