Alternative titles; symbols
SNOMEDCT: 699297004; ORPHA: 293707; DO: 0060289;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xq13.1 | Ohdo syndrome, X-linked | 300895 | X-linked recessive | 3 | MED12 | 300188 |
A number sign (#) is used with this entry because X-linked Ohdo syndrome (OHDOX) is caused by mutation in the MED12 gene (300188) on chromosome Xq13.
Maat-Kievit et al. (1993) described a boy (patient 2) with low weight, blepharophimosis, ptosis, broad and depressed nasal bridge, long flat philtrum, thin vermilion, microstomia, micrognathia, cryptorchidism, scrotum hypoplasia, joint hyperextensibility, clinodactyly, overriding third toes, cafe-au-lait spots, developmental delay, deafness, and feeding problems. The authors diagnosed the patient with Ohdo blepharophimosis syndrome.
Verloes et al. (2006) reported the 9-month-old maternal nephew of the patient reported by Maat-Kievit et al. (1993), who had died at age 25 years of metastatic carcinoma. The nephew had a similar phenotype. Verloes et al. (2006) classified the disorder in these patients as a distinct blepharophimosis-mental retardation syndrome, MKB (Maat-Kievit-Brunner) type, and suggested X-linked inheritance. They noted that whereas the MKB phenotype in infancy resembled that of the SBBYS variant of Ohdo syndrome (603736), the phenotype in adulthood was clearly distinct, with coarse facial features, thick alae nasi, triangular face, and a different gestalt from that in the SBBYS type.
Rubin et al. (2020) described 3 sibs of Moldavian descent with impaired intellectual development, characteristic facial features, and distal extremity anomalies. One of the sibs (III.3) had tetralogy of Fallot, which was repaired in infancy. He developed left-sided bronchiectasis at age 2 years, and had 3 episodes of pneumonia and recurrent otitis media. He subsequently developed right-sided bronchiectasis. He had global developmental delay, short stature, microcephaly, short palpebral fissures, and a small mouth. He had low CD19+ B-cell and CD3+ T-cell proliferation to mitogens, low IgG levels, and low antibody titers to S. pneumoniae and H. influenzae. Another sib (III.1) had recurrent otitis media, a low CD19+ count, and low antibody titers to S. pneumoniae. The third sib (III.4) had an atrioventricular canal defect with pulmonic stenosis, a low CD19+ count, and low IgM levels. Patients III.1 and III.4 had blepharophimosis and blepharitic keratopathy.
The transmission pattern of Ohdo syndrome in the families reported by Vulto-van Silfhout et al. (2013) was consistent with X-linked inheritance.
Vulto-van Silfhout et al. (2013) performed exome sequencing in 2 families segregating X-linked Ohdo syndrome, including the family originally studied by Maat-Kievit et al. (1993) and another family with 2 affected males, and identified hemizygous missense mutations in the MED12 gene (300188.0003-300188.0004) that segregated with the disorder in each family. By analysis of an additional cohort of 9 simplex male patients with Ohdo syndrome, they identified another MED12 missense mutation (300188.0005) in 1 patient.
By whole-exome sequencing in 3 brothers of Moldavian descent with Ohdo syndrome, Rubin et al. (2020) identified a hemizygous mutation in the MED12 gene (Q2159P; 300188.0006). The mother was heterozygous for the mutation. Functional studies were not performed.
Maat-Kievit, A., Brunner, H. G., Maaswinkel-Mooij, P. Two additional cases of the Ohdo blepharophimosis syndrome. Am. J. Med. Genet. 47: 901-906, 1993. [PubMed: 8279489] [Full Text: https://doi.org/10.1002/ajmg.1320470618]
Rubin, Z., Grange, D. K., Cooper, M. A. Siblings with a novel MED12 variant and Odho (sic) syndrome with immune defects. (Letter) Clin. Genet. 98: 308-310, 2020. [PubMed: 32715471] [Full Text: https://doi.org/10.1111/cge.13806]
Verloes, A., Bremond-Gignac, D., Isidor, B., David, A., Baumann, C., Leroy, M.-A., Stevens, R., Gillerot, Y., Heron, D., Heron, B., Benzacken, B., Lacombe, D., Brunner, H., Bitoun, P. Blepharophimosis-mental retardation (BMR) syndromes: a proposed clinical classification of the so-called Ohdo syndrome, and delineation of two new BMR syndromes, one X-linked and one autosomal recessive. Am. J. Med. Genet. 140A: 1285-1296, 2006. [PubMed: 16700052] [Full Text: https://doi.org/10.1002/ajmg.a.31270]
Vulto-van Silfhout, A. T., de Vries, B. B. A., van Bon, B. W. M., Hoischen, A., Ruiterkamp-Versteeg, M., Gilissen, C., Gao, F., van Zwam, M., Harteveld, C. L., van Essen, A. J., Hamel, B. C. J., Kleefstra, T., Willemsen, M. A. A. P., Yntema, H. G., van Bokhoven, H., Brunner, H. G., Boyer, T. G., de Brouwer, A. P. M. Mutations in MED12 cause X-linked Ohdo syndrome. Am. J. Hum. Genet. 92: 401-406, 2013. [PubMed: 23395478] [Full Text: https://doi.org/10.1016/j.ajhg.2013.01.007]