Alternative titles; symbols
ORPHA: 2363; DO: 0081371;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 4p16.3 | LADD syndrome 2 | 620192 | Autosomal dominant | 3 | FGFR3 | 134934 |
A number sign (#) is used with this entry because of evidence that lacrimoauriculodentodigital syndrome-2 (LADD2) is caused by heterozygous mutation in the tyrosine kinase domain of the FGFR3 gene (134934) on chromosome 4p16.
Lacrimoauriculodentodigital syndrome-2 (LADD2) is a multiple congenital anomaly disorder mainly affecting lacrimal glands and ducts, salivary glands and ducts, ears, teeth, and distal limb segments (summary by Rohmann et al., 2006).
Rohmann et al. (2006) described a father and his 2 children with LADD syndrome and a mutation in the FGFR3 gene. Features included alacrima, aplastic or hypoplastic ducts and puncta, conjunctivitis, small and cup-shaped ears, dental anomalies and caries, and hearing loss.
Talebi et al. (2017) described a mother and son with LADD syndrome from a consanguineous Iranian family. Aplasia, atresia, and hypoplasia of the nasolacrimal ducts and puncta resulted in conjunctivitis in both patients. The son also had hypodontia and microdontia. External ear anomalies included small, cup-shaped ears, and both patients had bilateral profound sensorineural hearing loss. Limb defects involved the thumbs, ranging from full aplasia to hypoplastic, digitalized, and duplicated thumbs. Mild syndactylies of toes or fingers and lower limb anomalies were also present. The mother's brother had been diagnosed with LADD syndrome but was not available for study.
The transmission pattern of LADD syndrome in the family reported by Rohmann et al. (2006) was consistent with autosomal dominant inheritance.
In affected members of a Turkish family (LADD-Ala) with LADD syndrome, Rohmann et al. (2006) identified a heterozygous missense mutation in the tyrosine kinase domain of the FGFR3 gene (D513N; 134934.0028).
In an affected mother and son in a consanguineous Iranian family with LADD syndrome, Talebi et al. (2017) identified heterozygosity for a missense mutation in the FGFR3 gene (D628N; 134934.0038).
Rohmann, E., Brunner, H. G., Kayserili, H., Uyguner, O., Nurnberg, G., Lew, E. D., Dobbie, A., Eswarakumar, V. P., Uzumcu, A., Ulubil-Emeroglu, M., Leroy, J. G., Li, Y., and 9 others. Mutations in different components of FGF signaling in LADD syndrome. Nature Genet. 38: 414-417, 2006. Note: Erratum: Nature Genet. 38: 495 only, 2006. [PubMed: 16501574] [Full Text: https://doi.org/10.1038/ng1757]
Talebi, F., Ghanbari Mardasi, F., Mohammadi Asl, J., Bavarsad, A. H., Tizno, S. Identification of a novel missence (sic) mutation in FGFR3 gene in an Iranian family with LADD syndrome by next-generation sequencing. Int. J. Pediat. Otorhinolaryng. 97: 192-196, 2017. [PubMed: 28483234] [Full Text: https://doi.org/10.1016/j.ijporl.2017.04.016]