Dental Enamel Hypoplasia Research Articles

Palaeopathology in late Pleistocene and early Holocene Central Plains bison: dental enamel hypoplasia, fluoride toxicosis and the archaeological record

Multiple formative agents are cited for dental enamel hypoplasia (DEH) in modern and fossil mammals. Here, four late Pleistocene-early Holocene bison assemblages from the Central Great Plains are analyzed for DEH and other bone pathologies to investigate the possible influence of chronic fluoride toxicosis, a condition that may have presented a long-term source of duress for prehistoric bison and devalued them as nutritional resources to human hunters. Although DEH is present in all the analyzed assemblages, the lack of corroborating dental and post-cranial anomalies consistent with chronic fluoride toxicosis speaks against it as a primary factor of DEH formation or general ill health in these bison. Rather, maternal nutritional stress, weaning, and seasonal forage condition are invoked as probable promoters of DEH formation. Other identified abnormalities are discussed in reference to their contribution to reduced feeding efficiency and lameness, as are their roles in developing palaeoecological models applicable to archaeological questions about ancient human lifeways.

Early childhood stress and adult age mortality—A study of dental enamel hypoplasia in the medieval Danish village of Tirup

This study explores how linear enamel hypoplasia (LEH) affects mortality in the village of Tirup (A.D. 1150-1350), Denmark. Data consist of information on 583 skeletons aged 1 year or more. Three partly overlapping subsamples were defined. (1) 104 skeletons of young children aged 1-6 years and 120 skeletons of adults giving information on LEH. (2) 458 skeletons aged 6 years or more. (3) 109 adult skeletons (aged 20 years or more) that provided transition analysis age estimates, sex assessments, and LEH information. Of the 109 skeletons in Subsample 3, 60 had no and 49 had at least one LEH. In Subsample 1, it was found that the case fatality rate for episodes potentially leading to LEH dropped from over 0.5 in 1-year olds to around 0.1 in 3-5-year olds. Only models with heterogeneity of frailty could describe late childhood and adolescent mortality. Further, it was shown that only a model with continuously varying frailty preserved heterogeneity to adulthood. Among young adult females and males in all adult ages, people with LEH experienced a higher mortality than people without it. Among males, the mortality rate ratio (MRR) was 2.28. The analyses indicate that the MRR gives an unbiased estimate for the extra risk of dying for adult males with LEH. The values of the case fatality rates for young children might be slightly biased upward because of a higher than average number of older children and adolescents dying with LEH.

Large forehead: A novel sign of undiagnosed coeliac disease

Background. The development of cranial proportions is the result of genetic, embriogenetic and environmental factors. Coeliac disease is a genetically inherited disease that is frequently diagnosed in adulthood in individuals, in whom the disease runs unidentified for years and can affect child growth from the moment of dietary gluten introduction up to the moment of gluten withdrawal following diagnosis. Data on the effects of gluten on craniofacial development in coeliac children are not available. Aim. The aim of the present study is to evaluate gluten-related effects on face development in patients with undiagnosed coeliac disease and their clinical relevance. Methods. The study was a prospective, multivariate analysis. Face photographs of adult patients with coeliac disease and healthy controls were marked at six reference points and distances and the ratios among distances were measured by computer program software. Results. The main finding of the study is that Caucasian Mediterranean adult coeliac individuals tend to have a peculiar aspect of the face characterised by a larger forehead when compared to general population controls. Conclusion. The craniofacial morphology of patients with coeliac disease reveals an altered pattern of craniofacial growth. This is the first report of alterations of craniofacial development in coeliac disease. This alteration is a clinical sign that should be included among the extraintestinal manifestation of coeliac disease. It has a frequency comparable to other signs or symptoms such as anaemia and short stature and is a better predictor of coeliac disease than other signs such as recurrent aphthous stomatitis, recurrent abortion and dental enamel hypoplasia. A large forehead is a sign easily evident visually or with very simple measurements; computer analysis is not required for the general practitioner. This sign along with the presence of other clinical signs and symptoms, should alert a physician to test a patient for coeliac disease.

Dental fluorosis and other enamel disorders in 12 year-old Nigerian children

The objectives were to determine the prevalence of dental fluorosis and other enamel disorders in the study population assess the degree of fluorosis and calculate the average number of teeth affected by different enamel disorders among 12 year old Nigerian children. The World Health Organization pathfinder methodology for oral health surveys was employed involving the index age 12 years. The target population was school children in the Mainland Local Government Area of Lagos State Nigeria. Two hundred children aged 12 years with equal number of boys and girls were examined. The childrens dentition were examined in a wet state for dental fluorosis tetracycline staining enamel hypoplasia enamel opacities and enamel mutilation. Dental fluorosis was present in 36.5% 21.5% had tetracycline stains 16.0% had enamel opacities 7.0% had enamel hypoplasia and 2.5% presented with enamel mutilation. Based on the Deans index 29.6% had very mild fluorosis and 7.5% had mild fluorosis. The average number of teeth affected by enamel defects in this study population was 10.8 teeth for tetracycline stain 6.3 teeth for enamel hypoplasia 4.6 teeth for enamel opacities and 1.0 tooth for enamel mutilation. The high prevalence of fluorosis suggests that the children are exposed to higher than optimal level of fluoride. It is therefore necessary to carry out further studies to determine the levels and sources of fluoride available to these children with the view to control the intake. This may involve the introduction of paediatric toothpastes with lower fluoride levels. The presence of tetracycline stains and enamel hypoplasia is indicative of a high level of childhood diseases. It is expedient that immunization against childhood diseases as well as health education and promotion efforts are intensified while restorative dental care is made available to the children to treat the enamel disorders. (authors)

Exploring the relationship between hypoplasia and odontometric asymmetry in Isola Sacra, an imperial roman necropolis

Anthropological studies reporting odontometric asymmetry values or dental enamel hypoplasia frequencies use these markers as a record of physiological perturbations occurring during dental development. While both markers indirectly suggest the amount of relative stress a population might have experienced, a relationship between the two has been explored only recently in the literature. In this study, we address the possibility of such a relationship in two ways. First, Kendall's tau B correlations test the degree of relationship on the level of the individual between hypoplasia presence/absence (P/A) and severity of hypoplasia appearance (PS) data for the anterior dentition and directional (DA) and fluctuating asymmetry (FA) data for concurrently developing molars pairs. Second, an F-test explores between-group (ranked hypoplastic individuals and non-hypoplastic individuals) variance about the mean, expecting the hypoplastic individuals to be more variable. The sample consists of 72 individuals from the Isola Sacra necropolis, which is associated with Portus, the port city of ancient Rome. Results indicated only a very weak predictive relationship between some variables and few significant differences in variation. However, variance follows trends in published literature. Possible explanations for the lack of interaction on the level of the individual include both etiological and genetic susceptibility factors that are significant in and of themselves as they suggest a more complex reading of the hard tissue evidence for stress in archaeological populations.

Environmental stress in the Early Mediaeval Slavic population at Borovce (Slovakia)

Several palaeopathological indicators examined in skeletal samples are caused by stress during childhood and remain visible in adults. In this study, dental enamel hypoplasia was observed in 451 individuals from the Early Mediaeval (8th to beginning of 12th c. AD) Slavic skeletal series at Borovce (Slovakia). The presence of enamel hypoplasia was scored in all types of deciduous and permanent teeth. More than one-fourth (27.2%) of the individuals with preserved permanent teeth showed enamel hypoplasia. No significant differences in the occurrence of the enamel lesions were found between males and females. The age at development of hypoplasias was estimated for 74 individuals by measuring the distance of the defect from the cemento-enamel junction. The hypoplastic defects appeared most frequently between 2.5 and 3.0 years. Following the trends observed in the distribution of age at development of the enamel lesions between subadults and adults, individuals stressed earlier in life had a reduced ability to cope with later insults. High prevalence of enamel hypoplasia, especially among 10–14-year-old growing juveniles, has led to the assumption that the Borovce population lived a considerably long period under conditions of high environmental pathogen load, and probably also suffered from some nutritional deficiencies.

An inter-site comparison of enamel hypoplasia in bison: implications for paleoecology and modeling Late Plains Archaic subsistence

Bison bison mandibular molars from the Late Plains Archaic kill/butchery sites of Buffalo Creek (Wyoming) and Kaplan-Hoover (Colorado) exhibit significant frequencies of dental enamel hypoplasia (DEH), a defect believed to reflect information about physiological status of individual animals. This study provides a methodology to estimate the ontogenetic and seasonal timing of DEH formation in bison dentition. Integration of these estimates with data from bison life history and grassland ecology allows inferences on age- and season-specific factors exacerbating periodic physiological declines that were recorded in the form of enamel hypoplasias. Differences between assemblages indicate regional variability in grassland conditions, with data from Buffalo Creek pointing to recurrent drought that reduced forage capacity and contributed to physiological stress in bison over two consecutive years. Seasons of physiological stress reflected in the DEH correspond to each of the three kill events at the locality, suggesting that predictability of bison behavior in this location was a critical factor in influencing the seasonal timing and location of repeated hunting episodes. Unlike Buffalo Creek, timings of stress episodes are not consistent with season of death in the Kaplan-Hoover bison assemblage, suggesting that favorable grassland conditions were the primary factor influencing timing of this large single-kill event in order to provision for the upcoming winter. DEH analysis represents a developing approach in the construction of models addressing key aspects of local grassland and bison ecology as well as offers unique insights into the hunting strategies and subsistence decisions of Late Plains Archaic foragers.

Leprosy and mortality in the Medieval Danish village of Tirup.

Leprosy was a well-recognized and dreaded disease in Denmark in the Middle Ages (AD 1000-1536). A large fraction of the population was affected by leprosy in the 13th century. This paper analyzes the correlation between signs of leprosy and risk of dying in the small Danish village of Tirup (AD 1150-1350). Seven different dichotomous osteological lesions indicative of leprosy are analyzed, and it is possible to score at least one of these conditions on 135 skeletons of adult or adolescent people (aged 14 or more). Scores were transformed to a statistic, lambda, indicating the likelihood that the person to whom the skeleton belonged suffered from leprosy. The analyses indicate that the prevalence of leprosy among adult people in Tirup was 26% (95% confidence interval, 17-35%). The lambda statistic indicates that people who died with signs of leprosy did not differ in the distribution of age at death from those who did not have such signs. Skeletons showing dental enamel hypoplasia were less likely to come from skeletons with high lambda-values. The association between lambda and dental enamel hypoplasia indicates a relationship between stress in early childhood (ages 1-6 years) and subsequent development of signs of leprosy.

Life stress on the Roman limes in continental Croatia

The purpose of the paper is to analyze and compare the demographic profiles and disease frequencies between a skeletal series from Zmajevac, a settlement on the Danubian limes, and a composite "non-limes" skeletal series consisting of human osteological remains from three large urban settlements to the west of the limes; roman Mursa (modern Osijek), Cibalae (Vinkovci) and Certissia (Strbinci). To determine if life stresses were different in settlements on the limes the age and sex distribution in Zmajevac was compared to the composite "non-limes" series. All skeletons were also analyzed for the presence of dental pathology, dental enamel hypoplasia, cribra orbitalia, trauma, and physical stress. Data collected from the skeletal series show that, with the exception of some indicators of physical stress, no significant differences in quality of life is evident. Both series are characterized by an under-representation of subadults from the youngest age category and by similar average adult male and female ages at death. In Zmajevac the average ages at death for adult males and females were 40.0 and 39.0 years respectively, in the composite "non-limes" series 37.4 years for both males and females. The frequencies of dental disease, subadult stress indicators, and trauma are similar in both series. The only consistent difference between the two series is noted in the frequencies of skeletal markers of physical stress, in particular the frequencies of vertebral osteoarthritis and Schmorl's defects. Total male and total female vertebral osteoarthritis frequencies in the two series are significantly different, as is the difference in total male frequencies of Schmorl's defects. Young adult males in the Zmajevac series seem to have been experiencing particularly heavy physical strain on the vertebral column. They exhibit significantly higher frequencies of both vertebral osteoarthritis and Schmorl's defects than young adult males from the composite non-limes series.

A Preliminary Assessment of Health and Disease in Human Skeletal Remains from Shi San Hang: A Prehistoric Aboriginal Site on Taiwan

A preliminary assessment of the health and disease of 23 (15 males and eight females) of the most complete and best preserved adult skeletons from the Shi San Hang site (ca 1800-500 B.P.), Taipei Prefecture, Taiwan, is made. Overall, the prehistoric inhabitants of Shi San Hang were relatively healthy. Adult mean statures indicate that the Shi San Hang adults were slightly taller than living Taiwan aboriginals. While moderately high frequencies of dental enamel hypoplasia (37.1%) and cribra orbitalia (38.9%) are observed in these remains, the overall health of these prehistoric inhabitants was good. Low frequencies of premortem tooth loss (0.3%), dental caries (1.0%), and dental abscessing (0.7%), and moderately low frequencies of periodontal disease observed in these remains suggest a mixed economy. Sex differences in the frequencies of some indicators in this prehistoric Taiwan aboriginal skeletal series suggest possible gender-related occupational/cultural uses of teeth. With the exception of spondylolysis in three individuals, bone trauma is rare. There is no evidence of general or specific infectious disease in these remains. Degenerative joint disease is not marked in the specimens examined. Limited comparisons of the results of this study are made with modern and prehistoric skeletal series from surrounding regions of Asia and the Pacific.

Type 1 Diabetes and Celiac Disease: Overview and Medical Nutrition Therapy

In patients with celiac disease (gluten-sensitive enteropathy, or GSE), ingestion of the gliadin fraction of wheat gluten and similar molecules (prolamins) from barley, rye, and possibly oats causes damage to the intestinal epithelium. The injury results from an abnormal T-cell response against gliadin. Thus, GSE is a disease in which host susceptibility must be combined with a specific environmental trigger to affect injury.1 Typically, patients with GSE have chronic diarrhea and failure to thrive. However, some patients present with short stature, flatulence, or recurrent abdominal pain. Dermatitis herpetiformis, a pruritic papular rash, is directly related to GSE.2 Other atypical presentations are increasingly recognized, among them iron-deficiency anemia, osteopenia/osteoporosis, short stature, dental enamel hypoplasia, arthritis and arthralgia, chronic hepatitis/hypertransaminasemia, and neurological problems. GSE has also been found in asymptomatic individuals who nonetheless have evidence of intestinal mucosal injury on biopsy.1 An association of diabetes with GSE has been observed since the late 1960s. In recent years, it has become clear that the incidence of GSE in patients with type 1 diabetes is substantial. A prevalence rate of 4–6% in type 1 diabetes has been reported.3–5 Some of the variation in prevalence can be attributed to the different diagnostic criteria used in the studies. The majority of patients with GSE are asymptomatic4 or are not aware of symptoms. Some patients present with problems recognized only retrospectively as resulting from celiac disease; it is common for “asymptomatic” patients to report improved health or sense of well-being when following a gluten-free diet. Up to one-third of patients may have unexplained failure to thrive, abdominal pain, or short stature.3,6 More controversial is the question of whether GSE affects blood glucose control. A study by Acerini et al.7 in a type 1 diabetic population found …

Preliminary Observations of Some Paleopathological Conditions in Historic and Modern Human Skeletal Remains from Ishigaki Island, Ryukyu Islands, Japan.

This study investigates some aspects of skeletal and dental paleo-pathology, including cribra orbitalia, dental enamel hypoplasia, trauma, osteoarthritis, periostitis and osteomyelitis. The sample consists of the skeletal remains of 33 individuals from the medieval and early modern periods, found on Ishigaki Island, Ryukyu Islands, Japan. High frequencies of cribra orbitalia and enamel hypoplasias suggest that the Ishigaki people may have experienced many severe nutritional deficiency stresses, infectious diseases, and/or parasitism during early childhood. This study further reports a markedly high frequency of periostitis and two cases of osteomyelitis in bones of the lower leg, probably the result of a specific infection, such as treponematosis.

Enamel hypoplasia in the deciduous teeth of great apes: variation in prevalence and timing of defects.

The prevalence of enamel hypoplasia in the deciduous teeth of great apes has the potential to reveal episodes of physiological stress in early stages of ontogenetic development. However, little is known about enamel defects of deciduous teeth in great apes. Unresolved questions addressed in this study are: Do hypoplastic enamel defects occur with equal frequency in different groups of great apes? Are enamel hypoplasias more prevalent in the deciduous teeth of male or female apes? During what phase of dental development do enamel defects tend to form? And, what part of the dental crown is most commonly affected? To answer these questions, infant and juvenile skulls of two sympatric genera of great apes (Gorilla and Pan) were examined for dental enamel hypoplasias. Specimens from the Powell-Cotton Museum (Quex Park, UK; n = 107) are reported here, and compared with prior findings based on my examination of juvenile apes at the Cleveland Museum of Natural History (Hamman-Todd Collection; n = 100) and Smithsonian Institution (National Museum of Natural History; n = 36). All deciduous teeth were examined by the author with a x10 hand lens, in oblique incandescent light. Defects were classified using Fédération Dentaire International (FDI)/Defects of Dental Enamel (DDE) standards; defect size and location on the tooth crown were measured and marked on dental outline charts. Enamel defects of ape deciduous teeth are most common on the labial surface of canine teeth. While deciduous incisor and molar teeth consistently exhibit similar defects with prevalences of approximately 10%, canines average between 70-75%. Position of enamel defects on the canine crown was analyzed by dividing it into three zones (apical, middle, and cervical) and calculating defect prevalence by zone. Among gorillas, enamel hypoplasia prevalence increases progressively from the apical zone (low) to the middle zone to the cervical zone (highest), in both maxillary and mandibular canine teeth. Results from all three study collections reveal that among the great apes, gorillas (87-92%) and orangutans (91%) have a significantly higher prevalence of canine enamel defects than chimpanzees (22-48%). Sex differences in canine enamel hypoplasia are small and not statistically significant in any great ape. Factors influencing intergroup variation in prevalence of enamel defects and their distribution on the canine crown, including physiological stress and interspecific dento-gnathic morphological variation, are evaluated.

Intensification of Agriculture at Ban Chiang: Is There Evidence from the Skeletons?

Human skeletal remains excavated in 1974 -1975 at Ban Chiang, a premetal to Bronze/Iron Age site located in northeastern Thailand, are used to examine the health effects of sedentism and agricultural intensification. The archaeological sequence provides evidence for the introduction of iron and water buffalo in the Middle period, suggesting the beginning of intensified agriculture. The effects of this agricultural intensification on the paleodemography, health, and patterns of traumatic injury of Ban ChiangÕs early inhabitants is examined. The skeletal and dental attributes examined include palaeodemographic parameters, dental caries, dental enamel hypoplasia, cribra orbitalia, stature, skeletal infections, and trauma. The results of this analysis are mixed. There are decreases in life expectancy and mean age-at-death that are consistent with a decline in health over time, but evidence for an increase in fertility, expected with intensified agriculture, is not found. Expected temporal increases in dental enamel hypoplasia and adult cribra orbitalia are documented. However, the expected decline in adult stature and expected increases in dental caries, cribra orbitalia in subadults, skeletal infection, and traumatic injury are not found. Overall, the skeletal indicators support continuity in Ban Chiang health, suggesting continuous reliance on a broadly based subsistence system. These findings do not fit the typical pattern demonstrated for other human groups experiencing the transition to sedentism and intensified agriculture and may support the contention that Southeast AsiaÕs archaeological sequence differs markedly from those studied elsewhere in the world.

Dental Paleopathology in a Serbian Medieval Population

Analysis of the pattern of dental disease in two Late Medieval populations from cemeteries excavated at archaeological sites in western Serbia was based on the study of tooth wear, ante-mortem tooth loss, caries, dental enamel hypoplasia, alveolar resorption, abscesses and calculus. The findings reported here show a high prevalence of attrition, alveolar resorption and caries, which suggest an abrasive diet and poor oral hygiene.

A disease-associated glycine substitution in BP180 (type XVII collagen) leads to a local destabilization of the major collagen triple helix.

BP180 is a homotrimeric transmembrane protein with a carboxy-terminal ectodomain that forms an interrupted collagen triple helix. Null type mutations in the BP180 gene produce a recessive subepidermal blistering disease, non-Herlitz junctional epidermolysis bullosa. Like the null mutations, a glycine substitution (G627V) within the longest BP180 collagenous domain (COL15) is also associated with the recessive skin disease; however, unlike the null mutations, this glycine substitution appears to act in a dominant fashion to give rise to a novel form of random pitting dental enamel hypoplasia. The dominant effects of this mutation were thought to be due to alterations in the assembly and/or stability of this BP180 collagenous region. To further investigate this issue, a structural analysis was performed on recombinant forms of the wild type and G627V mutant BP180 ectodomain. Both proteins were found to form collagen-like triple helices with very similar Stokes radii and melting temperatures and exhibited very similar rates of synthesis, secretion and turn-over. Tryptic digestion analysis revealed that the mutant G627V-sec180e contains an additional highly sensitive proteolytic site that maps within the region of the mutation. Thus, the disease-associated G627V mutation in BP180 does not grossly alter protein structure, but causes a local destabilization of the triple-helix that exposes sensitive residues to the in vitro effects of trypsin and possibly affects its structure-function in vivo.

Patterns of dental enamel defects at ancient Mendes, Egypt.

The dental remains of 88 individuals from Old Kingdom, First Intermediate, and Greco-Roman periods at the ancient Egyptian site of Mendes (Tell er-Rub(c)a) were examined for dental enamel hypoplasia, and the results reported here provide some of the first comparative data on enamel defects in ancient Egypt. Overall, 48% of the individuals in the sample have one or more teeth with hypoplasia, with 17% of permanent teeth and 8% of deciduous teeth affected. The permanent teeth account for 87% of the total number of affected teeth, a prevalence over deciduous teeth that is significant at alpha = 0.05. Permanent and deciduous teeth display different patterns of hypoplasia, with the former exhibiting both discrete pitting and linear furrowing, and the latter exhibiting only pits. Teeth with linear defects significantly outnumber those with pits by a factor of more than three to one. Only permanent canines display more than one lesion on a tooth, with a mean of 1.4 defects per affected tooth. Although calculation of the age of insult from lesion position is imprecise, it appears that stress episodes occurred most commonly between approximately 3-5 years of age. The presence of pits in the deciduous dentition, however, suggests that physiological stresses began in utero. There is no statistically significant difference in the frequency of enamel defects between males and females. An observed decrease in the frequency of defects from the Old Kingdom period to the subsequent First Intermediate and Greco-Roman periods is not significant at alpha = 0.05, although such a decrease is expected given epigraphic and other data that refer to prolonged drought and malnutrition in the late Old Kingdom. The calculated chi(2) value of 3.83 is significant at the 0.10 level, however, and since our sample is rather small and the magnitude of the chi-square statistic is a function of sample size, we recommend that future research investigate further the relationship between the frequency of enamel defects and the time period in which they occur.

Rapp-Hodgkin syndrome with palmoplantar keratoderma, glossy tongue, congenital absence of lingual frenum and of sublingual caruncles: Newly recognized findings

We report on a boy with Rapp-Hodgkin syndrome (RHS) or Rapp-Hodgkin ectodermal dysplasia. He had sparse, wiry, slow growing and uncombable hair, but no pili torti or pili canaliculi characteristic of RHS. He also had sparse eyelashes and eyebrows, and obstructed lacrimal puncta and epiphora. Bilateral bony external auditory canal stenosis led to hearing loss. The mouth was small with repaired bilateral cleft lip and palate. Oral manifestations included hypodontia, microdontia, unerupted mandibular premolars with well formed roots, large dental pulp spaces, enamel hypoplasia, multiple caries, glossy tongue, and congenital absence of lingual frenum and of sublingual caruncles including submandibular and sublingual salivary duct openings. Palmo-plantar keratoderma, unerupted premolars, congenital absence of lingual frenum, sublingual caruncles, glossy tongue, and pili canaliculi seen in the patient are newly recognized findings of this syndrome. Overlapping findings of RHS ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC), and ankyloblepharon-ectodermal defects-cleft lip and palate syndrome (AEC) are discussed.

Problems in the Methodology of Dental Enamel Hypoplasia Analyses

This article summarizes the issues and problems surrounding the subject of dental enamel hypoplasia (DEH). The methodology of several research studies, ranging from paleopathological to studies of living children, have been analysed and critiqued. The critiques are used to demonstrate where weaknesses may occur in this type of paleopathological study, and how they might be improved. This summary indicates that age formation and enamel development standards, and severity of the enamel disruption must be more carefully and universally applied to paleopathological and anthropological data. Standardized techniques for measurement of DEH are also essential for accurate and reliable research conclusions.

Evidence for genetic anticipation in the oculodentodigital syndrome

Oculodentodigital syndrome (O.D.) is an autosomal dominant disorder comprising facial anomalies, syndactyly, microcorneae, dental enamel hypoplasia, and leukodystrophy. We describe a four generation family with O.D. in which anomalies such as syndactyly appear congenitally, whereas neurological (i.e., leukodystrophic) signs and symptoms tend to be expressed in a more severe form and/or at an earlier age of onset in successive generations of the kindred. This pattern of phenotypic expression is consistent with the phenomenon of genetic anticipation, and we suggest that O.D. may be a trinucleotide repeat disorder. Am. J. Med. Genet. 71:36–41, 1997. © 1997 Wiley-Liss, Inc.