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On the Genetics of Hypodontia and Microdontia: Synergism Or Allelism of Major Genes in a Family with Six Affected Members

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On the Genetics of Hypodontia and Microdontia: Synergism Or Allelism of Major Genes in a Family with Six Affected Members JMed Genet 1996;33:137-142 137 On the genetics of hypodontia and microdontia: synergism or allelism of major genes in a family J Med Genet: first published as 10.1136/jmg.33.2.137 on 1 February 1996. Downloaded from with six affected members S P Lyngstadaas, H Nordbo, T Gedde-Dahl Jr, P S Thrane Abstract and epigenetic factors.7 In a large study oftooth Familial severe hypodontia of the per- number and size in British schoolchildren, ex- manent dentition is a rare condition. The cluding patients with more widespread ab- genetics ofthis entity remains unclear and normalities, Brook3 favoured a multifactorial several modes of inheritance have been model with a continuous spectrum, related to suggested. We report here an increase in tooth number and size, with thresholds, and the number of congenitally missing teeth where position on the scale depends upon the after the mating of affected subjects from combination of numerous genetic and en- two unrelated Norwegian families. This vironmental factors, each with a small effect. condition may be the result of allelic mut- In this study the proportion ofaffected relatives ations at a single gene locus. Alternatively, varied with the severity of the condition in the incompletely penetrant non-allelic genes probands and an association between hy- may show a synergistic effect as expected podontia and microdontia was noted. for a multifactorial trait with interacting Other causes of hypodontia have been sug- gene products. This and similar kindreds gested and include an evolutionary trend to- may allow identification of genes involved wards fewer teeth,28 infections during in growth and differentiation of dental tis- pregnancy and early childhood, hormonal dys- sues by linkage and haplotype association function, which itself may be inherited, and analysis. Brittle nails, delayed growth of various environmental factors.7 the hair, and delayed teething in the prob- There are indications that different genetic ands support the grouping of these con- mechanisms control the development of per- ditions among the ectodermal dysplasias. manent succedaneous and molar teeth.9 The Laboratory for (7Med Genet 1996;33:137-142) permanent molars result from a posterior Molecular Biology, growth of the dental lamina in the last months Department of Oral Key words: brittle nails; brittle hair; ectodermal dys- http://jmg.bmj.com/ Pathology, plasia; familial hypodontia. of fetal life continuing into the first years after Faculty of Dentistry, birth. The succedaneous tooth on the University of Oslo, buds, PO Box 1109, other hand, are formed concomitantly with the Blindern, Hypodontia is interesting to the human ge- primary dentition in early fetal life, but further N-0317 Oslo, Norway neticist development is arrested until The S P Lyngstadaas because it constitutes one of the most birth.'01' P S Thrane widespread polymorphisms in man. 1 Few mode and site ofgene action are also unknown. dental traits have commanded more attention Animal studies have suggested that hypodontia Department of among the general arises when the cell mass of an on September 30, 2021 by guest. Protected copyright. Preclinical population and the dental undeveloped Techniques, Dental profession than hypodontia.2 The mechanisms tooth germ falls below a critical size.'2 Teeth Faculty, underlying hypodontia remain obscure. Con- are typical examples of organs developing from University of Oslo, genitally missing teeth tend to run in families.3 epithelial and mesenchymal tissues. Their PO Box 1109, Blindern, Some investigators consider hypodontia to be growth and morphogenesis are regulated by a N-0317 Oslo, Norway the result of a single dominant gene. The clas- number of growth factor genes expressed in H Nordbo sicial family study ofhypodontia was performed these two tissue components.'3 Therefore, ab- Institute of Forensic by Grahnen4 on parents and sibs of 171 affected errations in one or more of these basic genes Medicine and persons. He concluded that, in the majority of regulating epithelial-mesenchymal interactions Department of cases, hypodontia is mainly determined by a during the growth ofteeth could play important Dermatology, Rikshospitalet, dominant autosomal gene pattern with in- roles in hypodontia. Medical Faculty, complete penetrance and variable expressivity. Severe hypodontia is most often observed in University of Oslo, Other studies suggest autosomal recessive and association with certain inherited disorders and N-0027 Oslo, Norway sex T Gedde-Dahl Jr linked inheritance patterns5 or favour a syndromes such as cherubism (familial fibrous polygenic hypothesis.6 dysplasia of the jaw),'4 Kallin syndrome,'516 Department of In a review on the inheritance patterns of incontinentia pigmenti, ' and the ectodermal Pathology, congenital The Norwegian absence ofteeth, Graber2 concluded dysplasias (ED).'8-20 Occasionally, hypodontia Radium Hospital, that severe hypodontia is a result of defects in is observed in persons with no other external Montebello, a closely linked polygenic system that regulates signs of hereditary disease. Such "non-syn- N-0310 Oslo, Norway the timing and spatial P S Thrane development of dental dromic" dental agenesis is seldom an isolated tissues, most often transmitted in an autosomal phenomenon; rather it appears to be linked to Correspondence to: dominant pattern with incomplete penetrance other dental changes such as microdontia and Dr Lyngstadaas. and variable expressivity. reduced crown size of Received 28 June 1995 the remaining teeth,32' Revised version accepted for There are indications that different types of taurodontism,22 and the overal rate of dental publication 12 October 1995 hypodontia may be caused by different genetic development.623 In a study on 167 patients 138 Lyngstadaas, Nordbo, Gedde-DahlJ3r, Thrane J Med Genet: first published as 10.1136/jmg.33.2.137 on 1 February 1996. Downloaded from 7 [t)&t) 1 & ta 1t 1 \ 1 ~~~~~~~~~~~~~~~~~~Delayedteething \ B~~Dljatyged hair growth 38 r-~~~~~-----1 ~ I l 38,35I I 8,41,1,4,4\ ~~~~Taurodontism III 1 1 1 1 1 etin * E l l818,15,14,12,2225,28I~~~~~~~~~~~~~~~~~~~~elyd Dlyegeehn 0° * (i) Cong hip dislocation Taurodontism Unaffected Affected Partly affected Carrier by Asthma deduction Figure 1 Pedigree of the family in which six cases of hypodontia and microdontia were found. Note the aggravation of the conditon after mating of two differently affected persons. The probands, marked with arrows, also have other ectodermal symptoms. Symptoms are given under each affected subject. with hypodontia and 135 healthy controls, congenitally missing permanent teeth. Their Schalk-van der Weide et al24 found no clear mother has two other affected relatives, an associations between congenitally missing teeth uncle and a niece, but there are no other known and other ectodermal symptoms. However, cases in the family of the father (fig 1). they concluded that if the number of missing The probands, their parents, and their chil- teeth is large or if the most stable teeth, that dren as well as their affected relatives were is, the maxillary central incisors and the first examined clinically and radiographically at the molars, are missing, the patient should be ex- Dental Hospital, University of Oslo. amined carefully for symptoms of ectodermal dysplasia. http://jmg.bmj.com/ We present here a Norwegian family where CLINICAL INFORMATION (TABLE) hypodontia was aggravated after the mating of Probands unrelated affected subjects. The probands also Case 1, the older sister, was examined in 1970, have other ectodermal signs. The inheritance aged 8 years, and again in 1993, aged 31 of this particular condition and a putative as- years. Bilateral congenital hip dislocation was sociation with ectodermal dysplasia are dis- corrected surgically in early childhood, and she cussed. had experienced an asthmatic condition. Onset on September 30, 2021 by guest. Protected copyright. of her scalp hair growth was within the normal range. Her scalp hair is abundant and blonde, Materials, methods, and results with a colour not differing conspicuously from FAMILY HISTORY that of her unaffected relatives. She has no The families, both white Norwegian, are not current symptoms in her skin, hair, nails, eye- related, and appear normal, both physically, brows, sweat secretion, tear secretion, eyes, mentally, and socially. All members ofthe famil- or hearing. Her facies and maxillomandibular ies receive regular dental care by private dent- relationship are normal. ists. Both oral examinations showed a mixed den- The families, consisting of 50 people in four tition with primary as well as permanent teeth generations (fig 1), were asked to fill in ques- present. The morphology of both primary and tionnaires and agreed to make their dental permanent teeth appeared normal, but when records available through their private dentists. compared to the mean values reported for white All family members, except the youngest prob- populations10 a significantly reduced mesio- and, had developed normal primary dentition, distal diameter of the crowns of 11 (6 8 mm), but six cases ofcongenitally missing permanent 21 (6-5 mm), and 23 (6-1 mm) was noted. teeth were reported. Except for the conditions Eruption of the succedaneous teeth is severely observed in the probands, no other signs of delayed (fig 2a). No visible malformations or hereditary disorders were reported in these aberrations in other oral tissues were found. families. The probands, two sisters, were re- Radiographic examination showed that
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