ORPHA: 974; DO: 0060227;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 4p15.2 | Adams-Oliver syndrome 3 | 614814 | Autosomal dominant | 3 | RBPJ | 147183 |
A number sign (#) is used with this entry because of evidence that autosomal dominant Adams-Oliver syndrome-3 (AOS3) can be caused by heterozygous mutation in the RBPJ gene (147183) on chromosome 4p15.
Hassed et al. (2012) described an autosomal dominant form of Adams-Oliver syndrome involving characteristic vertex scalp defects and terminal limb defects, but without congenital heart defects, other associated defects, or immune defects.
For a discussion of genetic heterogeneity of Adams-Oliver syndrome, see AOS1 (100300).
Hassed et al. (2012) reported 2 families segregating autosomal dominant Adams-Oliver syndrome. In the first family, the female proband was noted to have cutis aplasia at birth and syndactyly of her second and third toes but otherwise normal extremities. She had microcephaly, short palpebral fissures, and mild motor delay. Her father had microcephaly, borderline mental retardation, and short distal phalanges of the fingers, with absent toes and short metatarsals bilaterally. In the second family, there were 8 affected individuals over 3 generations, including a mother with shortened distal phalanges of the left hand, bilateral reduction of the toes, and normal intelligence, who had a daughter with cutis aplasia, asymmetric shortening of the hands bilaterally, asymmetric reductions of the feet, and intellectual deficits, and a mildly affected son with fifth-finger nail aplasia, fifth-toe shortening, and normal development. The mother's brother had mild limb reductions of his hands and normal intelligence. Neither family had heart defects, immune defects, or other associated anomalies.
The transmission pattern of AOS3 in the families reported by Hassed et al. (2012) was consistent with autosomal dominant inheritance.
Using a variant-filtering strategy to perform exome resequencing in 2 unrelated families with Adams-Oliver syndrome, Hassed et al. (2012) identified 2 different heterozygous missense mutations in the RBPJ gene (147183.0001 and 147183.0002) that segregated with disease in each family.
Hassed, S. J., Wiley, G. B., Wang, S., Lee, J.-Y., Li, S., Xu, W., Zhao, Z. J., Mulvihill, J. J., Robertson, J., Warner, J., Gaffney, P. M. RBPJ mutations identified in two families affected by Adams-Oliver syndrome. Am. J. Hum. Genet. 91: 391-395, 2012. [PubMed: 22883147] [Full Text: https://doi.org/10.1016/j.ajhg.2012.07.005]