Alternative titles; symbols
ORPHA: 96148; DO: 0060390;
Cytogenetic location: 10q26 Genomic coordinates (GRCh38): 10:117,300,001-133,797,422
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 10q26 | Chromosome 10q26 deletion syndrome | 609625 | Autosomal dominant | 4 |
A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome on chromosome 10q.
Lewandowski et al. (1978) first reported a patient with partial deletion of chromosome 10q. Shapiro et al. (1985) reported 8 unrelated patients with deletions of various segments of chromosome 10q.
Mehta et al. (1987) reported a boy with deletion of chromosome 10q26. He showed developmental delay and moderate mental retardation. Physical characteristics included short stature, microcephaly, dolichocephaly, triangular face, prominent nasal root with beaked nose and flared nostrils, long philtrum, small pointed jaw, and convergent strabismus. He also had fifth finger clinodactyly, limited elbow extension, and undescended testes. All who worked with him noted hyperkinesis and aggressive behavior with limited attention span and diminished need for sleep. He alternated between being provocative or destructive and affectionate.
Tanabe et al. (1999) reported a male infant with a de novo terminal deletion of chromosome 10q26.11. He had multiple anomalies including beaked nose, malformed and low-set ears, short and webbed neck, low posterior hairline, widely spaced nipples, limited left elbow extension, cryptorchidism, small penis, and hypoplastic scrotum. Patent ductus arteriosus was also present. In a review of the literature, Tanabe et al. (1999) stated that 25 patients had been reported. Ten (83%) of 12 males with chromosome 10q deletions had cryptorchidism.
Irving et al. (2003) reported 8 familial and 4 de novo cases of terminal 10q deletion syndrome, and 3 cases with interstitial deletion of 10q25.2-q26.3. One family had 6 affected members with terminal deletion of 10q26.2-ter, and the oldest living individual was 63 years old. Common features included facial asymmetry, prominent nose, thin upper lip, strabismus, low birth weight, short stature and fifth finger clinodactyly. Variable degrees of learning difficulty were found in 11 patients, and four had seizures. Four patients had violent mood swings and aggression, whereas 2 had affectionate behavior. Visceral abnormalities were uncommon: 3 patients had renal anomalies, 2 with vesicoureteral reflux and 1 with acute renal failure of unknown etiology, and 2 patients had an atrial septal defect. Only 2 patients were male, both of whom had cryptorchidism. Irving et al. (2003) suggested that the consistent clinical findings supported the existence of a distinct 10q deletion syndrome, as had been suggested by Wulfsberg et al. (1989) and Schrander-Stumpel et al. (1991).
Courtens et al. (2006) described a 13-year-old girl with a de novo subterminal 10q26.2 deletion of approximately 6.1 Mb and typical clinical findings of monosomy 10qter syndrome, including mental retardation, pre- and postnatal growth retardation, microcephaly at birth, and strabismus. The authors reviewed the clinical and behavioral phenotype of 15 reported patients with 'pure' subterminal 10q deletion.
Miller et al. (2009) reported 4 unrelated children with de novo heterozygous deletions of the chromosome 10q25.3 to 10qter region. All had variable dysmorphic facial features, delayed psychomotor development, and poor speech and language development. The first girl had frontal bossing, widow's peak, strabismus, stellate irides, and bilateral fifth finger clinodactyly. She walked at 20 months; at age 3 years she had an unsteady gait and could only speak 4 words. FISH analysis followed by SNP studies identified a 6.1-Mb deletion at chromosome 10q26.2-qter on the paternal chromosome. The second girl had strabismus, mild epicanthal folds, a mildly recessed columella, tapered fingers, and axial hypotonia. By 14 months of age, she was not walking independently, babbling, or speaking. She also had a 6.1-Mb deletion at chromosome 10q26.2-qter that was 57 kb larger than that found in the first child. The third child was a boy with failure to thrive, triangular face, brachycephaly, long broad forehead, strabismus, hypotelorism, small nose with a prominent nasal bridge, hypoplastic toenails, and hypotonia. He also had bilateral congenital sensorineural hearing loss with multiple inner ear malformations involving both the cochlear and vestibular organs. He had a 12.4-Mb deletion at chromosome 10q26.12-qter, involving at least 78 genes. The fourth child was a boy with ambiguous genitalia with bilateral cryptorchidism, failure to thrive, prominent metopic suture, bitemporal narrowing, prominent eyes, bilateral epicanthal folds, downslanting palpebral fissures, prominent ears, and mild micrognathia with a high-arched palate. He also had congenital sensorineural hearing loss, craniosynostosis, and inner ear structural abnormalities. He had an interstitial deletion at chromosome 10q25.3-q26.13 encompassing about 46 genes on the paternal chromosome. The 2 patients with the largest deletions had loss of the HMX2 (600647) and HMX3 (613380) genes, which may play a role in the hearing loss and structural abnormalities of the inner ear.
Yatsenko et al. (2009) reported 5 individuals from 4 families with distal 10q deletion syndrome. The familial cases involved a 25-year-old man who had history of bilateral hip dysplasia, anxiety disorder, learning difficulties, and mildly dysmorphic facial features, including triangular face, prominent nose, low-set ears, and micrognathia. His affected 2-year-old daughter had failure to thrive, developmental delay, dislocated hip, poor speech development, and similar dysmorphic features as her father. Array CGH analysis showed a heterozygous interstitial 5.8-Mb deletion of chromosome 10q26.12-q26.2 in both father and daughter. The 3 unrelated patients had a variety of congenital defects, including dysmorphic facies, patent ductus arteriosus, genitourinary anomalies, mental retardation, and attention-deficit hyperactivity disorder. One also had autistic features. The smallest region of overlap in all affected individuals was an approximately 600-kb segment at 10q26.2, encompassing the DOCK1 (601403) and C10ORF90 (617735) genes. The common features among these patients were craniofacial dysmorphism, various degrees of mental retardation, and generalized growth failure. One patient with genitourinary anomalies, including ambiguous genitalia and imperforate anus, had a larger 15 to 20-Mb deletion of chromosome 10q25.13-q26.3. Yatsenko et al. (2009) hypothesized that haploinsufficiency for the DOCK1 gene, which is involved in multiple signaling pathways, may underlie the phenotypic variability in this disorder.
Among a cohort of 41 patients with hypotonia, ataxia, and delayed development syndrome (HADDS; 617330), which is caused by mutation in the EBF3 gene, Deisseroth et al. (2022) identified 2 patients with 10q deletion disrupting the EBF3 gene. From a review of 47 reported patients with HADDS, they found 5 additional patients with a 10q26 deletion.
Courtens, W., Wuyts, W., Rooms, L., Pera, S. B., Wauters, J. A subterminal deletion of the long arm of chromosome 10: a clinical report and review. Am. J. Med. Genet. 140A: 402-409, 2006. [PubMed: 16419133] [Full Text: https://doi.org/10.1002/ajmg.a.31053]
Deisseroth, C. A., Lerma, V. C., Magyar, C. L., Pfliger, J. M., Nayak, A., Bliss, N. D., LeMaire, A. W., Narayanan, V., Balak, C., Zanni, G., Valente, E. M., Bertini, E., Benke, P. J., Wangler, M. F., Chao, H. T. An integrated phenotypic and genotypic approach reveals a high-risk subtype association for EBF3 missense variants affecting the zinc finger domain. Ann. Neurol. 92: 138-153, 2022. [PubMed: 35340043] [Full Text: https://doi.org/10.1002/ana.26359]
Irving, M., Hanson, H., Turnpenny, P., Brewer, C., Ogilvie, C. M., Davies, A., Berg, J. Deletion of the distal long arm of chromosome 10q; is there a characteristic phenotype? A report of 15 de novo and familial cases. Am. J. Med. Genet. 123A: 153-163, 2003. [PubMed: 14598339] [Full Text: https://doi.org/10.1002/ajmg.a.20220]
Lewandowski, R. C., Jr., Kukolich, M. K., Sears, J. W., Mankinen, C. B. Partial deletion 10q. Hum. Genet. 42: 339-343, 1978. [PubMed: 669716] [Full Text: https://doi.org/10.1007/BF00291317]
Mehta, L., Duckett, D. P., Young, I. D. Behaviour disorder in monosomy 10qter. J. Med. Genet. 24: 185-186, 1987. [PubMed: 3573005] [Full Text: https://doi.org/10.1136/jmg.24.3.185]
Miller, N. D., Nance, M. A., Wohler, E. S., Hoover-Fong, J. E., Lisi, E., Thomas, G. H., Pevsner, J. Molecular (SNP) analyses of overlapping hemizygous deletions of 10q25.3 to 10qter in four patients: evidence for HMX2 and HMX3 as candidate genes in hearing and vestibular function. Am. J. Med. Genet. 149A: 669-680, 2009. [PubMed: 19253379] [Full Text: https://doi.org/10.1002/ajmg.a.32705]
Schrander-Stumpel, C., Fryns, J. P., Hamers, G. The partial monosomy 10q syndrome: report on two patients and review of the developmental data. J. Ment. Defic. Res. 35: 259-267, 1991. [PubMed: 1920392] [Full Text: https://doi.org/10.1111/j.1365-2788.1991.tb01059.x]
Shapiro, S. D., Hansen, K. L., Pasztor, L. M., DiLiberti, J. H., Jorgenson, R. J., Young, R. S., Moore, C. M. Deletions of the long arm of chromosome 10. Am. J. Med. Genet. 20: 181-196, 1985. [PubMed: 3970071] [Full Text: https://doi.org/10.1002/ajmg.1320200122]
Tanabe, S., Akiba, T., Katoh, M., Satoh, T. Terminal deletion of chromosome 10q: clinical features and literature review. Pediat. Int. 41: 565-567, 1999. [PubMed: 10530074] [Full Text: https://doi.org/10.1046/j.1442-200x.1999.01105.x]
Wulfsberg, E. A., Weaver, R. P., Cunniff, C. M., Jones, M. C., Jones, K. L. Chromosome 10qter deletion syndrome: a review and report of three new cases. Am. J. Med. Genet. 32: 364-367, 1989. [PubMed: 2658586] [Full Text: https://doi.org/10.1002/ajmg.1320320319]
Yatsenko, S. A., Kruer, M. C., Bader, P. I., Corzo, D., Schuette, J., Keegan, C. E., Nowakowska, B., Peacock, S., Cai, W. W., Peiffer, D. A., Gunderson, K. L., Ou, Z., Chinault, A. C., Cheung, S. W. Identification of critical regions for clinical features of distal 10q deletion syndrome. Clin. Genet. 76: 54-62, 2009. [PubMed: 19558528] [Full Text: https://doi.org/10.1111/j.1399-0004.2008.01115.x]