Amelogenesis Imperfecta, Type Ia
A number sign (#) is used with this entry because of evidence that amelogenesis imperfecta type IA (AI1A) is caused by heterozygous mutation in the beta-3 laminin gene (LAMB3; 150310) on chromosome 1q32.
DescriptionHypoplastic amelogenesis imperfecta IA is characterized by enamel that may not develop to normal thickness. The enamel may have pits on the labial or buccal surfaces that are often arranged in rows and columns (see Witkop, 1989).
Clinical FeaturesKim et al. (2013) described 2 unrelated families of Turkish and Iranian descent, respectively, with autosomal dominant hypoplastic amelogenesis imperfecta. The proband in Family 1 was a 6.5-year-old girl who presented with sensitive teeth. The enamel of both her primary and secondary dentition was thin, with deep grooves and pitting defects. The enamel was generally more radiopaque than dentin. Taurodontism was evident in both the primary and secondary molars. Her mother, whose dentition was described as normal, reported that the proband's father had dental problems, but he was not available for study. Family 1 had previously been reported as family AI-23 by Kim et al. (2006). The proband in Family 2 presented with enamel hypoplasia of all teeth. She had thermal sensitivity and her tooth enamel showed deep grooves and pits. Radiographs showed little or no taurodontism. Her mother and maternal aunt had a similar phenotype.
Poulter et al. (2014) described a 4-generation Irish family (AI-17) segregating autosomal dominant hypoplastic amelogenesis imperfecta. The 3-year-old proband presented with generalized, irregular hypoplastic amelogenesis imperfecta, with small islands of enamel evident on close inspection and evidence of posteruptive changes. Affected family members experienced pain and aesthetic problems with their teeth, and some had had extensive restorative dental care and multiple extractions. None of those affected had other health problems or skin manifestations.
InheritanceThe transmission pattern of amelogenesis imperfecta in the families reported by Kim et al. (2013) and Poulter et al. (2014) was consistent with autosomal dominant inheritance.
Molecular GeneticsBy whole-exome sequencing in 2 families with autosomal dominant amelogenesis imperfecta, Kim et al. (2013) identified truncating mutations in the LAMB3 gene (150310.0017 and 150310.0018) that segregated with the disorder in each family.
By whole-exome sequencing in a 4-generation Irish family (AI-17) segregating amelogenesis imperfecta, Poulter et al. (2014) identified a truncating mutation in the LAMB3 gene (150310.0019) that segregated with the disorder in the family.
HistoryAmelogenesis imperfecta is an inherited defect of dental enamel formation that shows both clinical and genetic heterogeneity. There may be more than one distinct form of autosomal dominant hypoplastic amelogenesis imperfecta. For example, Witkop and Rao (1971) listed smooth, rough and pitted forms, as well as a local form. In the smooth hypoplastic type, many teeth fail to erupt and multiple calcifications of the pulp often occur, even in unerupted teeth. Numerous enameloid conglomerates are found histologically in areas of unerupted teeth. Witkop and Sauk (1976) enumerated 6 forms of hypoplastic amelogenesis imperfecta. Four--the pitted, local, smooth and rough forms--are autosomal dominant. In addition, there is probably an autosomal recessive rough type and an X-linked smooth type (301200). The dental anomaly designated generalized microdontia by Steinberg et al. (1961) is the hypoplastic type of amelogenesis imperfecta. The pedigree of the family they reported is consistent with either autosomal or X-linked dominant inheritance.