In this form of selective tooth agenesis, the upper lateral incisors are absent or peg-shaped. The latter feature is a partial expression of the gene. The trait was present in one-third of a Swiss group studied by Joehr ... In this form of selective tooth agenesis, the upper lateral incisors are absent or peg-shaped. The latter feature is a partial expression of the gene. The trait was present in one-third of a Swiss group studied by Joehr (1934). Furthermore, all affected members of the isolate were descendants of one man, born in the 18th century. Woolf (1971) found that in 71 of 103 families of probands with missing maxillary lateral incisors, one or more first-, second-, or third-degree relatives had a missing or peg-shaped maxillary incisor. He concluded that at least part of the genetic component is autosomal dominant with reduced penetrance and variable expressivity. Families showed a high degree of intrafamilial concordance for type of minor anomaly, especially if the proband had bilaterally absent lateral incisors. Adolph H. Schultz (1891-1976), distinguished anthropologist (Biegert, 1976), gave an early report of an affected family he observed personally on the occasion of a large gathering. A peculiarity was that only females were affected and only females transmitted the trait. Sometimes vestigial lateral incisors in parents were followed by complete absence in children and then reappearance of vestigial incisors in the third generation. Witkop (1987) reported 2 kindreds in which 3 individuals (2 in one family and 1 in the second) had agenesis of the succedaneous (permanent, or secondary) teeth. Both parents in each family had pegged or missing maxillary lateral incisors. In the offspring with the missing succedaneous teeth, permanent molar teeth were present. Witkop (1987) suggested that agenesis of the succedaneous teeth results from the homozygous state of the gene determining the trait for small/pegged/missing maxillary lateral incisors. Witkop (1987) stated that the prevalence of the small-pegged-missing incisor trait in the United States is approximately 1 in 67 (1.5%) and estimated that, on this basis, the prevalence of agenesis of succedaneous teeth should be about 1 in 18,000. Anodontia of permanent teeth unassociated with a syndrome is inherited as an autosomal recessive (206780). Nieminen et al. (1995) reported 5 Finnish families with incisor and premolar hypodontia. The diagnosis in the probands was based on congenital absence of 1 to 4 teeth or the presence of 1 or more peg-shaped incisors. All members of the family were studied clinically and panoramic tomograms were taken. Hypodontia of deciduous dentition was assessed anamnestically. Nieminen et al. (1995) referred to this disorder as incisor and premolar hypodontia because of the teeth that are most often affected, and placed the prevalence of this type of hypodontia at 5 to 10% among European and Asian populations. Hoo (2000) reported a family with 2 sibs with anodontia of permanent teeth. Both parents had normal dentition, but the paternal grandmother, her twin sister, and a paternal aunt all had only 2 maxillary incisors, and the maternal grandmother had only 2 mandibular incisors. The author concluded that this family provides further evidence for the hypothesis of Witkop (1987) that agenesis of permanent teeth is a homozygous state of the gene responsible for pegged or missing maxillary lateral incisors.
In patients with a recessive form of ectodermal dysplasia (OODD; 257980) caused by mutation in the WNT10A gene (606268), Bohring et al. (2009) observed a pattern of tooth anomalies comparable to that seen in patients with anodontia of ... In patients with a recessive form of ectodermal dysplasia (OODD; 257980) caused by mutation in the WNT10A gene (606268), Bohring et al. (2009) observed a pattern of tooth anomalies comparable to that seen in patients with anodontia of permanent dentition (206780) and selective tooth agenesis-4, and suggested that testing for mutations in WNT10A might be worthwhile in the latter patients. In an American family with variable hypodontia involving the lateral incisors and premolar teeth, Kantaputra and Sripathomsawat (2011) analyzed the candidate gene WNT10A and identified heterozygosity for a missense mutation (F228I; 606268.0003) in the father, who had congenitally absent maxillary first premolars and 3 third molars, and his oldest son, who had absent maxillary permanent lateral incisors and mandibular second premolars. A second son, who had absence of the maxillary permanent lateral incisors, mandibular second premolars, and a mandibular permanent lateral incisor, was heterozygous for a different missense mutation (D217N; 606268.0007) that he inherited from his mother, who had normal dentition. A third son, who was compound heterozygous for the mutations, had only microdontia of the left mandibular second molar. None of the family members had other manifestations of ectodermal dysplasia. Van den Boogaard et al. (2012) identified WNT10A mutations in 19 (56%) of 34 unrelated patients with nonsyndromic tooth agenesis (see, e.g., 606268.0002-606268.0004), 8 of whom were homozygous, 4 compound heterozygous, and 7 heterozygous for the mutations. MSX1 (142983), PAX9 (167416), and AXIN2 (604025) mutations were present in 3%, 9%, and 3% of the patients, respectively. The authors concluded that WNT10A is a major gene in the etiology of isolated hypodontia.