Amelogenesis Imperfecta, Hypomaturation Type, Iia1

A number sign (#) is used with this entry because of evidence that this form of pigmented hypomaturation-type amelogenesis imperfecta (AI2A1) is caused by homozygous mutation in the kallikrein-4 gene (KLK4; 603767) on chromosome 19q13.

Description

Autosomal recessive amelogenesis imperfecta pigmented hypomaturation type is characterized by enamel of normal thickness that is hypomineralized and has a mottled appearance. The slightly soft enamel detaches easily from the dentin, and radiographs show a lack of contrast between enamel and dentin (Witkop, 1989).

Genetic Heterogeneity of the Hypomaturation Type of Amelogenesis Imperfecta

See also AI2A2 (612529), caused by mutation in the MMP20 gene (604629); AI2A3 (613211), caused by mutation in the WDR72 gene (613214); and AI2A4 (614832), caused by mutation in the C4ORF26 gene (614829).

Clinical Features

Witkop (1965) reported 2 families with autosomal recessive pigmented hypomaturation AI. In 1 of the families, a brother and sister were affected. The disorder involved both the primary and the secondary dentitions. The teeth had a shiny agar jelly appearance and the enamel was softer than normal. The usual radiographic contrast between enamel and dentin was lacking. Histologically a brown pigment, which was probably not derived from blood pigments, was demonstrable in the middle layers of enamel. The parents, who were first cousins once removed, and more remote relatives were unaffected.

Witkop et al. (1973) reported 2 sisters with autosomal recessive pigmented hypomaturation AI.

Hart et al. (2004) reported 2 African American female sibs with hypomaturation AI. Both primary and permanent dentitions were affected, showing a yellow-brown discoloration. The teeth were excessively sensitive to hot and cold, making it painful to masticate. Radiographically the teeth appeared morphologically normal, indicating that the enamel was of normal thickness. The enamel showed only a slightly increased opacity compared with the dentin, indicative of a decreased enamel mineral content. Enamel had fractured from the occlusal surfaces of the primary molars, consistent with a decreased mineral content. One child had an anterior dental open bite.

Wang et al. (2013) described a 9-year-old girl from Turkey with an isolated hypomaturation form of amelogenesis imperfecta. The girl's parents were first cousins and had normal-appearing enamel. The proband's teeth appeared normal in size and shape but showed brown discoloration and chipping. She was secondarily affected with dental caries but had no anterior open bite. Radiographically, the enamel was of normal thickness and showed slight contrast with dentin.

Comparison of AI2A1 and AI2A2

Kim et al. (2005) compared the dental phenotypes of the KLK4 (Hart et al., 2004) and MMP20 (their study) probands and noted many similar features. The enamel crowns are normal in size and shape, have a rougher, duller, less reflective surface than normal enamel, appear to be more brittle in that they show a tendency to fracture or chip, but do not appear to be particularly susceptible to dental caries. The radiodensity of the defective enamel is generally less than that of normal enamel, but can still be distinguished from the underlying dentin on radiographs. The coloration of the teeth is different, but extrinsic staining since tooth eruption could have contributed to the current appearance. The KLK4 teeth have a more homogeneous dark yellow hue, while the MMP20 teeth have an irregular grayish brown discoloration and are a little more glossy. Overall, the dental phenotypes in the KLK4 and MMP20 probands are remarkably similar.

Molecular Genetics

In 2 African American sibs with AI2A1, Hart et al. (2004) identified a homozygous nonsense mutation in the KLK4 gene (W153X; 603767.0001). Wright et al. (2011) identified the same mutation in 2 affected members of an unrelated African American family with amelogenesis imperfecta.

In a 9-year-old Turkish girl with AI2A1, Wang et al. (2013) identified a homozygous deletion in the KLK4 gene (603767.0002) Her first-cousin parents were heterozygous for the mutation.