Amelogenesis Imperfecta, Type Iv

A number sign (#) is used with this entry because amelogenesis imperfecta, hypomaturation-hypoplastic type, with taurodontism can be caused by mutation in the DLX3 gene (600525).

Clinical Features

Congleton and Burkes (1979) and Crawford et al. (1988) described amelogenesis imperfecta of the hypomaturation-hypoplasia type with taurodontism. The dental findings were apparently identical to those of trichodentoosseous syndrome (TDO; 190320), from which it differed only by the lack of changes in the hair and bones. Crawford and Aldred (1990) reviewed all reported cases of these disorders, obtaining additional information from the original authors. They concluded that 'if the teeth are affected in the absence of hair or bone changes, either in the individual or within the family, then the diagnosis should be deemed to be AI H-H T.' Seow (1993) suggested that true taurodontism, as indicated by a change in the mandibular first permanent molar, occurs only in TDO syndrome and that this feature can be used to differentiate clearly between TDO and AI. However, Wright et al. (1997) found taurodontism in the first molars in TDO to be variable and not an inherently good delineator between AI and TDO.

Contributing to the confusion between AIHHT and TDO is the fact that TDO has a highly variable clinical phenotype. While enamel hypoplasia and taurodontism appear to be present in all TDO cases, nondental features may be absent, with approximately half of TDO patients losing the kinky/curly hair phenotype seen in infancy by adolescence, and in almost 20% of cases, osseous changes are not evident (Price et al., 1999).

Wright et al. (1997) found that at least 1 of the families reported by Congleton and Burkes (1979) had TDO by both phenotype and genotype and that, based on geographic proximity, the other 2 families reported by Congleton and Burkes (1979) likely had TDO.

Inheritance

Amelogenesis imperfecta of the hypomaturation-hypoplasia type with taurodontism (AIHHT) is inherited as a highly penetrant autosomal dominant trait.

Molecular Genetics

Price et al. (1999) presented molecular evidence that AIHHT is separate from TDO. The genetic basis for TDO was shown to be a deletion mutation in the distal-less 3 (DLX3; 600525) transcription factor gene. Price et al. (1999) performed mutation analysis and sequencing studies of the DLX3 gene and of the linked paralogous gene on chromosome 17, DLX7, in affected members of a family with AIHHT. No mutations or polymorphisms in the exons of either gene were found in AIHHT.

In affected members of a 3-generation family in which AIHHT occurred in an autosomal dominant pedigree pattern, Dong et al. (2005) identified a 2-bp deletion in the DLX3 gene (560delCT; 600525.0002).

Wright et al. (2008) analyzed the DLX3 gene in a 3-generation family with an attenuated TDO phenotype and identified heterozygosity for the 560delCT mutation in all affected individuals. Noting that affected individuals in this kindred had changes in hair, tooth, and bone, although to a lesser degree than individuals with the the DLX3 4-bp deletion (600525.0001), the authors concluded that this mutation causes TDO with an attenuated phenotype, not AIHHT, as previously reported.