Three successive generations of women with anhidrotic/hypohidrotic ectodermal dysplasia

We describe the findings of anhidrotic/hypohidrotic ectodermal dysplasia in three successive generations of a family. All three women had variable alopecia, anhidrosis, hypodontia and malar hypoplasia. Chromosomal studies revealed a defect of the 2q12 region in all three patients. Previous studies have reported rare cases of autosomal dominant ectodermal dysplasia associated with defects in the 2q11-13 region1. These rare disorders are characterized by common anomalies of at least two elements of the ectoderm and its appendages--namely, the skin, teeth, hair, nails and sweat glands. These patients also frequently have chronic dental problems with early loss of teeth and recurrent lung, ear and nose infections secondary to a defect in mucous membrane function. The majority of reported cases of ectodermal dysplasias have historically been X-linked recessive, but our findings indicate that an autosomal version may be more prevalent than previously thought.     

Eruption age of teeth in Nigeria

Present study was carried out on 1,022 boys and 646 girls of various age groups. In this study, an attempt has been made to estimate the eruption age of teeth in various age groups, ranging from 6 to 23 years in Northern Nigerian population. From the data collected a mean have been provided for the eruption age of each tooth. The differences noticed in the eruption ages between boys and girls are not very marked. However, a few points of interest may be mentioned. The lateral incisor, first premolar and Canine erupt earlier amongst girls. The first molar and the central incisor seem to erupt earlier among boys than girls. The teeth of the lower jaw erupt before those of the upper jaw. The Nigerian's wisdom teeth erupt with some constancy between 14-21st years. The third molar tooth fails to erupt in 5% individuals. The second premolar was absent in 0.5% populations.     

Aplasia cutis congenita, congenital heart lesions, and frontonasal cysts in four successive generations

We report a family with four known generations of individuals in the maternal family tree with aplasia cutis congenita (ACC) of the scalp, congenital heart lesions, brachydactyly, and frontonasal cysts. This is the first reported finding of craniofacial, digital, and cardiac abnormalities associated with ACC, likely representing a new variant of the autosomal dominant hidrotic ectodermal dysplasia subtype. These rare disorders are characterized by common anomalies of at least two elements of the ectoderm and its appendages, namely the skin, teeth, hair, nails, and sweat glands. These patients also frequently have chronic dental problems with early loss of teeth, and recurrent lung, ear, and nose infections secondary to a defect in mucous membrane function. The clinical findings in these patients are delineated and compared to patients with other forms of ectodermal dysplasia in the literature.     

A longitudinal study of growth in Newcastle upon Tyne adolescents

White Newcastle upon Tyne schoolchildren born in 1962 were examined at approximately half-yearly intervals from 9 to 17 years of age. During the last year of compulsory education losses to follow-up became selective with respect to socio-economic background, and the results reported here are restricted to 564 boys and 669 girls seen regularly between the ages of 10 and 15 years at least. Newcastle adolescents were slightly shorter and lighter than the London children on whom Tanner's British Standards were based. The longitudinal pattern of skinfold changes in boys was different from that observed in girls. Differences in height attained between occupational groups were well established by the age of five years, and the same was true of differences between family-size groups for children with fathers in manual occupations. It is inferred that differences in height between occupational and family-size groups resulted more from differences in leg than in trunk length. At age 15, the correlations of height attained with maternal height were 0.42 and 0.43, and with birthweight 0.25 and 0.28, for boys and girls respectively. Adjustment, by regression, of heights attained for birthweight, age at peak height velocity and maternal height diminished differences between occupational and family-size groups. After such adjustment, heights significantly lower than average were found only among subjects with fathers in unskilled manual occupations and with large families. Among subjects with fathers in manual occupations, subscapular and triceps skinfolds and arm circumference decreased significantly with increasing family size.     

A new method for assessment of dental maturity using the individual curve of number of erupted permanent teeth

A new method for the evaluation of dental age in healthy children, using the curve of the total number of erupted permanent teeth, is presented. The method is based on the observation that the curves of the total number of teeth erupted are parallel and similar in shape in different individuals provided that logarithms are used for both age and number of erupted teeth. The chronological age for a specific reference point on the eruption curve was determined graphically in individual subjects. At this age each child has reached the same degree of dental maturity. A group of 133 healthy boys and 137 girls was examined annually for seven years. The mean age at the reference point of the tooth eruption curve was 8.75 years for the boys and 8.44 years for the girls.     

Effect of under-nutrition on permanent tooth emergence among Rajputs of Himachal Pradesh,India

Background: The sequence and emergence of permanent teeth are considered to be largely under genetic control. However, some environmental factors have also been reported to influence tooth emergence.

Aim: To investigate the effect of under-nutrition on the emergence of permanent teeth in a sample of Rajput children from part of Solan District in Himachal Pradesh State of India.

Subjects and methods: This study is based on a cross-sectional sample of 509 school-going boys and girls ranging in age from 5–14 years. The emergence of the first 28 teeth was investigated. The nutritional status of each subject was evaluated using stature and weight expressed as SD scores of weight-for-age, stature-for-age and weight-for-stature of the NCHS reference data.

Results: Mandibular teeth tended to emerge earlier than the maxillary teeth in both sexes and, except pre-molars, emergence was earlier in girls. Simple correlation between number of emerged teeth and stature (0.871 in girls, 0.855 in boys) and weight (0.814 in girls, 0.791 in boys) was significant (p ≤ 0.05), but on partialling out the effect of age, values of partial correlation were low and not significant. Under-nourished children of both sexes (those with SD scores of ? 2 SD or less) had fewer erupted teeth compared to normal children (with SD scores of ? 1 SD and over), according to weight-for-age as well as stature-for-age. However, the differences were less marked in older age groups, that is those above 11 years. When the number of emerged teeth was analysed according to weight-for-stature there was no clear difference in the number of emerged teeth between under-nourished (wasted) and normal children.

Conclusions: Past long-term and chronic under-nutrition may result in delayed emergence of permanent teeth, particularly in younger age groups.     

Morbidity in early childhood: differences between girls and boys under 10 years old.

The aim of the study was to investigate the differences in presented morbidity and use of health services among boys and girls in early childhood. The study was performed using data collected by the continuous morbidity registration project of the department of general practice at Nijmegen University. All recorded morbidity, referrals to specialists and admissions to hospitals were recorded by the registration project. The study population included children born in four practices from 1971 to 1984. The children were followed up until the age of five years and if possible until the age of 10 years. The morbidity of the children had been categorized into three levels of seriousness of diagnosis and 15 diagnostic groups as part of the registration project. Boys presented more morbidity than girls in the first years of their lives. For the age group 0-4 years this was true for all levels of seriousness of diagnosis except the most serious. In this younger age group significantly more boys than girls suffered respiratory diseases, behaviour disorders, gastroenteritis and accidents. Girls suffered from more episodes of urinary infection than boys in both age groups. More boys were referred to specialists and admitted to hospital than girls. The findings of this study suggest that not only inborn factors can explain the sex differences in presented morbidity and use of health services in early childhood. In particular, differences between girls and boys in terms of non-serious morbidity and referral and admission rates suggest a different way of handling health problems in boys and girls in early childhood both by parents and doctors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases

Hypohidrotic and anhidrotic ectodermal dysplasia (HED/EDA) is a rare genodermatosis characterized by abnormal development of sweat glands, teeth, and hair. Three disease-causing genes have been hitherto identified, namely, (1) EDA1 accounting for X-linked forms, (2) EDAR, and (3) EDARADD, causing both autosomal dominant and recessive forms. Recently, WNT10A gene was identified as responsible for various autosomal recessive forms of ectodermal dysplasias, including onycho-odonto-dermal dysplasia (OODD) and Sch?pf-Schulz-Passarge syndrome. We systematically studied EDA1, EDAR, EDARADD, and WNT10A genes in a large cohort of 65 unrelated patients, of which 61 presented with HED/EDA. A total of 50 mutations (including 32 novel mutations) accounted for 60/65 cases in our series. These four genes accounted for 92% (56/61 patients) of HED/EDA cases: (1) the EDA1 gene was the most common disease-causing gene (58% of cases), (2)WNT10A and EDAR were each responsible for 16% of cases. Moreover, a novel disease locus for dominant HED/EDA mapped to chromosome 14q12-q13.1. Although no clinical differences between patients carrying EDA1, EDAR, or EDARADD mutations could be identified, patients harboring WNT10A mutations displayed distinctive clinical features (marked dental phenotype, no facial dysmorphism), helping to decide which gene should be first investigated in HED/EDA.     

Height and height velocity in early, average and late maturers followed to the age of 25: a prospective longitudinal study of Swedish urban children from birth to adulthood

A sample of 103 Swedish boys and 80 Swedish girls followed longitudinally were grouped into early, average and late maturers on the basis of age at peak height velocity. In girls there were significant differences in height between the maturity groups from 5 to 14 years of age, but the final height did not differ between the groups. In boys there were significant differences in height between the maturity groups from 12 to 16 years, no significant difference at the age of 17 years, and from 18 years of age and on, late-maturing boys were significantly taller than the early maturity boys. From 21 years and onwards they were also taller than the average-maturing boys. Thus final height differed significantly between the late-maturing boys and the other two maturity groups of boys, averaging 6.5 cm and 4.2 cm, respectively.     

Twenty-four cases of the EEC syndrome: clinical presentation and management.

Twenty-four cases of EEC syndrome were identified as part of a nationwide study. Ectodermal dysplasia, by study definition, was present in all cases and hair and teeth were universally affected. Nail dysplasia was present in 19 subjects (79%) and the skin was affected in 21 (87%). The presence of hypohidrosis was not noted as a predominant feature in the syndrome and its occurrence appeared to depend on the presence of all other features. Distal limb defects from simple syndactyly to tetramelic cleft hand and foot were identified, including preaxial anomalies. Orofacial clefting was identified in 14 cases (58%) and lacrimal duct anomaly in 21 (87%). Significant clinical problems encountered were chiefly cosmetic or ophthalmological, but conductive deafness and genitourinary problems in some cases required surgical intervention. Altered self-image was also noted in some cases. Multidisciplinary management is necessary with the early involvement of the clinical geneticist. Developmentally, the EEC syndrome and related disorders represent disorders of ectodermal/mesodermal interaction. Candidate regions include 7q21.3, the "ectrodactyly" locus; other candidates include developmental genes implicated in the ectodermal/mesodermal interactive process.     

Standard RUS skeletal maturation of Tokyo children

A total of 704 girls and 753 boys, all healthy, from 3 to 18 years of age, from Tokyo and its suburbs, were radiographed on the left hand and wrist in 1986. Their RUS (TW2) skeletal maturity was estimated, the 50th-centile skeletal maturity scores were obtained, and the smoothed RUS maturity curves were determined applying the cubic spline function to the 50th-centile scores. On this maturity curve the score at each 0·1 year of chronological age was obtained and allocated as a given RUS skeletal age. This set of scores and ages we termed the TW2-J RUS, i.e. the Japanese TW2 RUS maturity standard. Comparing this RUS standard with the British standard, the Belgian, the southern Chinese, and the northern Indian, it became clear that Japanese children's RUS skeletal maturity progresses rapidly during puberty (after ages 9 in girls and 11 in boys), and that the maximum score difference between neighbouring age groups was observed at ages 12·5 in girls and 14·5 in boys on the spline-smoothed curve. Japanese children attain the adult stage 1 or 2 years earlier than other groups of children (at ages 15 in girls and 16 in boys).     

A syndrome of hypohidrotic ectodermal dysplasia with normal teeth, peculiar facies, pigmentary disturbances, psychomotor and growth retardation, bilateral nuclear cataract, and other signs.

This paper describes a 7-year-old girl with trichodysplasia, normal teeth, onychogryposis, hypohidrosis, psychomotor and growth retardation, dry and warm skin with follicular hyperkeratosis, pigmentary disturbances (hyper- and hypochromic spots), bilateral nuclear cataract, dermatoglyphic anomalies, and other signs. This condition is considered a new form of ectodermal dysplasia.     

Novel EDAR mutation in tooth agenesis and variable associated features

Tooth agenesis (TA) is the developmental absence of one or more permanent teeth. We report on 10 members of a Pakistani family afflicted with TA with variable associated features inherited in autosomal dominant fashion with full penetrance. The malformation is bilateral in the majority of cases, and hallmark feature is the absence of lateral and central incisors and canines whereas first and second premolars are involved less often. Affected individuals also have pronounced variable features associated with TA such as diastema between central incisors, overgrown labial frenum, peg-shaped lower incisors, delayed exfoliation, over-erupted upper incisors and malocclusion but have no other signs of ectodermal dysplasia. Through linkage analysis coupled with exome sequencing, we identified novel nonsense variant EDAR c.1302G>A, p.(Trp434*). The variant is deduced to create a premature termination codon that leads to the deletion of the 15 C-terminal residues. Heterozygous EDAR variants most commonly cause hypohydrotic ectodermal dysplasia, but recently one nonsense and 10 missense variants have been reported in nonsyndromic TA, some with few mild features of hypohydrotic ectodermal dysplasia. The phenotype in the family we present, the largest with EDAR-related TA reported to date, is highly variable and without any signs of ectodermal dysplasia.     

Activity pattern,smoking habits,and somatometric variables of the Czechoslovakian population

Summary A total of 3762 subjects of both sexes, natives of Czechoslovakia, ranging in age from 12–55 years, were examined. Both anamnestic data and selected anthropometric variables were evaluated. The proportion of non-smokers for adult males was 47–56%, and for adult females was 54–74% of the population. The proportion of subjects not engaged in any type of physical activity decreases in boys between 12 and 18 years from 28 to 16%, in girls between 12 and 15 years from 25 to 22%; from then on the trend reverses and the percentage rises up to 42% in men and 65% in women. The number of subjects participating in competitive sporting activity reaches its peak at 18 years, when 46% of boys and 43% of girls compete, but than decreases quickly. 12 year old girls are taller and heavier than boys but at 15 years the relationship is reversed. The LBM at the age of 12 is equal in boys and girls, but from then till 18 years the increase is larger in boys. The LBM weight in adults remains steady, women attaining 77% of the value found in men. The skinfold increases with age similarly in both sexes, except for an interval between 12 and 18 years, when girls show a steeper increase. Adult women attain 121–160% of the values characteristic for men. The grip strength of the right hand equals about 50 kp in adult men and 30 kp in adult women. Within the age range followed, it remains unaffected by age.More than 50 specialists assisted in gathering the pertinent data     

Variants of the ectodysplasin A1 receptor gene underlying homozygous cases of autosomal recessive hypohidrotic ectodermal dysplasia

Hypohidrotic ectodermal dysplasia (HED) is a rare genetic condition resulting from defective development of ectodermal derivatives, such as hair, teeth, and sweat glands. Autosomal recessive (AR) forms of HED may be caused by pathogenic variants of the ectodysplasin A1 receptor (EDAR) gene that encodes a receptor involved in the NF-κB signaling pathway. Here, we describe three cases of AR-HED in families of Turkish, Austrian, and German-American origin (with or without known consanguinity). In these cases, two out-of-frame deletions and a pathogenic missense variant of EDAR were found to be disease-causing due to reduced availability of the respective messenger RNA or impaired interaction of the encoded protein with its binding partner leading to diminished signal transduction. The same missense variant, c.1258C>T (p.Arg420Trp), has actually been reported to be restricted to the Icelandic population and to be associated with non-syndromic tooth agenesis but not HED. As our patient has no known relationship to Icelandic individuals and displays a rather severe HED phenotype, we suggest that EDAR-Arg420Trp is a more widespread variant, possibly with variable clinical expressivity.     

Skeletal maturity in Belgian youths assessed by the Tanner-Whitehouse method (TW2)

Reference data for skeletal maturity (TW2 method) of the hand and wrist are provided for large representative samples of Belgian boys and girls. The sample of Belgian boys consisted of 21 174 boys aged 12 to 20 years studied in a nationwide cross-sectional and longitudinal study on the physical fitness of secondary schoolboys (1969–1974). The girls' sample consisted of 9698 6–19-year-old Flemish girls studied cross-sectionally (1979–1980). Both samples were multi-stage stratified cluster samples of entire school classes. All skeletal maturity assessments of the boys were made by the same observer (GB). His estimations agreed quite closely with those of the originators of the method. The skeletal age assessments of the girls were made by two observers trained by GB. Both observers showed high intra-observer reliability after training, and during the assessments. Moreover their ratings compared favourably with those of GB and the originators of the method.

Smoothed percentile curves of the maturity scores (TW2-20 bone, RUS and CARP scores) were calculated by means of cubic splines using a stepwise regression procedure for the selection of suitable knots. In the boys, the TW2 scores (20 bone and RUS) increase linearly between 12 and 14·5 years of age, slow down for a while, and then increase again, while the CARP scores increase linearly between 12 and 15 years of age. In girls, the 20-bone maturity scores increase nearly linearly from 6 through 9·5 years of age, accelerate until 11·0 years followed by a smaller increase; RUS scores increase curvilinearly from 6 years of age onwards; and Carp scores increase almost linearly between 6·0 and 12·5 years of age. Belgian boys are advanced in RUS scores but are delayed for the carpal bones as compared with the British standards. The Belgian girls show advancement for both scales as compared with the British reference data. The skeletal maturation of youths from several other continental European countries corresponds more closely with the Belgian than with the British data. The reference data presented herein most probably provide suitable standards for youths of West-European countries.     

Cross-sectional reference values for height, weight and body mass index of school children living in Tehran, Iran

AIM: The aim of the study was to create reference values for weight, height and body mass index (BMI) of school children living in Tehran. METHOD AND SAMPLES: The study subjects consisted of 1,420 girls between 6 and 17 years of age and 1,515 boys between 6 and 15 years of age. Samples were collected by a multistage sampling method from schools in different areas of Tehran. All participants were established to be healthy and their height, weight and BMI evaluated. Reference standard values estimated by the LMS method using LMS Light software and 3rd, 5th, 10th, 25th, 50th, 75th, 90th, 97th and 85th (only for BMI) centiles were constructed and the results compared with US reference values. RESULTS: The centiles provided a good fit to the data. In boys, there were some significant differences of mean standard deviation scores (SDS) of height and BMI from zero, but there were no significant differences in weight. In girls, the mean SDS of height, weight and BMI were significantly lower than zero, especially for 7-9 years of age. Among 12-13-year-old girls, the mean SDS of height, weight and BMI came closer to zero, and the differences were not significant. Thereafter, although girls seemed to be shorter than US reference measures, their weight and BMI did not differ from reference values significantly. CONCLUSION: Our results for boys between 6 and 15 years are comparable with US reference values; however, the US reference values, especially for height, are not applicable for Iranian girls between 6 and 17 years.     

Tooth emergence in Australian Aboriginals

Patterns of dental development in 125 Australian Aboriginal boys and girls, in a growth study at Yuendumu in the Northern Territory of Australia, were compared with Australians of European origin using mean tooth emergence curves constructed from the emergence times of right and left side permanent teeth. There were two active phases of tooth emergence separated by a quiescent period of 1.4 years in boys and 1.0 years in girls. Phase one included emergence of the first 12 teeth, that is the first permanent molars and all incisors; phase two included emergence of the canines, premolars and second molars. In Aboriginal girls most teeth emerged earlier than in boys. Compared with the European-descended, the Aboriginal children displayed earlier emergence of most teeth during phase two and a shorter quiescent period between the two phases, an emergence pattern similar to that reported in other non-European populations. In Aboriginals the process tooth emergence and subsequent alignment is aided by adequate space and compensatory bone growth growth in the alveolar regions. These factors, as well as the genetic differences between groups, contribute to the earlier emergence of teeth during phase two in the Aboriginal children.     

The prevalence of X-linked hypohidrotic ectodermal dysplasia (XLHED) in Denmark, 1995–2010

X-linked hypohidrotic ectodermal dysplasia (XLHED) is characterised by hypohidrosis, sparse hair, and teeth abnormalities. Infants with XLHED have an increased risk of death by hyperpyrexia. XLHED is the most common form of hypohidrotic ectodermal dysplasia (HED); however, no population-based prevalence estimates are available. We aimed to: 1) estimate the prevalence of XLHED in the Danish population per January 1, 2011; 2) identify the most frequent age at time of diagnosis; and 3) quantify the most frequent clinical feature associated with XLHED.Materials and methodsWe conducted a nationwide cross-sectional study (1995–2010). We leveraged national medical registries and data from clinical departments to categorise XLHED cases into three groups: 1) Molecularly-confirmed XLHED; 2) Clinically-diagnosed HED (registered with ICD-10 Q 82.4); and 3) Possible HED (registered with sufficient clinical features based on a clinical algorithm that we designed).ResultsWe identified 90 molecularly-confirmed XLHED, 146 clinically-diagnosed HED, and 988 possible HED cases between 1995 and 2010 (total n = 1224). The prevalence was 21.9 per 100,000 overall and 1.6 per 100,000 when restricting to molecularly-confirmed XLHED cases. The most frequent age at time of XLHED diagnosis occurred between the ages of 11 and 18 years. Teeth abnormalities occurred in 79% of all cases and 52% of molecularly-confirmed cases as a primary clinical marker.ConclusionWe present the first ever population-based prevalence estimates of XLHED and suggest that the prevalence of XLHED may be higher than previously estimated. Diagnosis occurs most frequently during adolescence and teeth abnormalities were the most frequent clinical marker of XLHED.