Alternative titles; symbols
ORPHA: 2149, 98892; DO: 0050454;
Cytogenetic location: 5q14.3-q15 Genomic coordinates (GRCh38) : 5:83,500,001-98,900,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 5q14.3-q15 | Periventricular nodular heterotopia 5 | 612881 | 4 |
A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome.
Cardoso et al. (2009) reported 3 unrelated children, 2 boys and a girl, with severe mental retardation, epilepsy, and bilateral periventricular heterotopia limited to the subependymal region of the temporal and occipital horns of the lateral ventricles. Other features included hypotonia, delayed motor development, no speech acquisition, and minor dysmorphic facial features, such as high forehead, depressed nasal bridge, and hypertelorism. One of the patients also showed polymicrogyria on brain MRI.
Using array CGH, Cardoso et al. (2009) identified a de novo deletion of chromosome 5q14.3-q15 in 3 unrelated patients with periventricular heterotopia. The deletions ranged in size from 6.3 to 17 Mb, and shared a common deleted region spanning 5.8 Mb. Computational analysis of the critical region identified 14 candidate genes.
Sobreira et al. (2009) identified a 7.4-Mb deletion on chromosome 5q14.3-q21 (chr5:90,787,099-98,232,469, NCBI36) in an 11-year-old boy with intellectual disability, bilateral iris coloboma, hearing loss, dental anomaly, and dysmorphic facial features (613443), but without periventricular heterotopia. Sobreira et al. (2009) referred to the report by Cardoso et al. (2009), who identified a deleted region on the overlapping region 5q14 in patients with periventricular heterotopia. One of those patients had a unilateral coloboma and shared part of the deletion with the patient reported by Sobreira et al. (2009). Comparison of the shared deleted regions between the 2 patients delineated a putative 2.6-Mb region for coloboma (95,538,699-98,232,465 bp) and a putative 1.84-Mb region for periventricular heterotopia (88,945,075-90,787,099 bp).
Le Meur et al. (2010) reported 5 unrelated children with severe mental retardation, absent speech, and stereotypic movements (613443) who each had a different interstitial de novo deletion of chromosome 5q14 ranging in size from 216 kb to 8.8 Mb. The minimal common deleted region contained only the MEF2C gene (600662). Le Meur et al. (2010) noted that the 5q14 region partially overlapped with that deleted in patients with periventricular heterotopia reported by Cardoso et al. (2009), but that only 1 of those patients had deletion of the MEF2C gene. Moreover, none of the patients reported by Le Meur et al. (2010) had periventricular heterotopia.
Al-Kateb et al. (2013) reported an 8-year-old boy with a de novo 582-kb deletion on chromosome 5q15 (chr5:92,742,875-93,324,350, hg18), which included 5 genes. They compared the findings in their patient with those in the 3 patients reported by Cardoso et al. (2009) and the patient reported by Brown et al. (2009), all of whom shared a minimal overlapping region of about 230 kb (chr5:92,742,875-92,972,632) encompassing 2 genes: FLJ42709 and NR2F1 (132890). All 5 patients had developmental delay and facial dysmorphic features, 4 had hypotonia, and 3 had ophthalmologic abnormalities. Ureteropelvic obstruction was observed only in their patient. Periventricular heterotopia was present only in the patients reported by Cardoso et al. (2009). Al-Kateb et al. (2013) suggested that NR2F1 was the strongest candidate gene for the overlapping phenotypes. Heterozygous mutations in the NR2F1 gene have been identified in patients with Bosch-Boostra-Schaaf optic atrophy syndrome (615722), characterized by developmental delay, moderate intellectual disability, and optic atrophy.
Al-Kateb, H., Shimony, J. S., Vineyard, M., Manwaring, L., Kulkarni, S., Shinawi, M. NR2F1 haploinsufficiency is associated with optic atrophy, dysmorphism and global developmental delay. (Letter) Am. J. Med. Genet. 161A: 377-381, 2013. [PubMed: 23300014] [Full Text: https://doi.org/10.1002/ajmg.a.35650]
Brown, K. K., Alkuraya, F. S., Matos, M., Robertson, R. L., Kimonis, V. E., Morton, C. C. NR2F1 deletion in a patient with a de novo paracentric inversion, inv(5)(q15q33.2), and syndromic deafness. Am. J. Med. Genet. 149A: 931-938, 2009. [PubMed: 19353646] [Full Text: https://doi.org/10.1002/ajmg.a.32764]
Cardoso, C., Boys, A., Parrini, E., Mignon-Ravix, C., McMahon, J. M., Khantane, S., Bertini, E., Pallesi, E., Missirian, C., Zuffardi, O., Novara, F., Villard, L., Giglio, S., Chabrol, B., Slater, H. R., Moncla, A., Scheffer, I. E., Guerrini, R. Periventricular heterotopia, mental retardation, and epilepsy associated with 5q14.3-q15 deletion. Neurology 72: 784-792, 2009. [PubMed: 19073947] [Full Text: https://doi.org/10.1212/01.wnl.0000336339.08878.2d]
Le Meur, N., Holder-Espinasse, M., Jaillard, S., Goldenberg, A., Joriot, S., Amati-Bonneau, P., Guichet, A., Barth, M., Charollais, A., Journel, H., Auvin, S., Boucher, C., Kerckaert, J.-P., David, V., Manouvrier-Hanu, S., Saugier-Veber, P., Frebourg, T., Dubourg, C., Andrieux, J., Bonneau, D. MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations. J. Med. Genet. 47: 22-29, 2010. [PubMed: 19592390] [Full Text: https://doi.org/10.1136/jmg.2009.069732]
Sobreira, N., Walsh, M. F., Batista, D., Wang, T. Interstitial deletion 5q14.3-q21 associated with iris coloboma, hearing loss, dental anomaly, moderate intellectual disability, and attention deficit and hyperactivity disorder. Am. J. Med. Genet. 149A: 2581-2583, 2009. [PubMed: 19876902] [Full Text: https://doi.org/10.1002/ajmg.a.33079]