Congenital malformations in Japanese macaques (Macaca fuscata) at Takasakiyama

From the late 1960s to the early 1970s, many congenitally malformed infants were born into provisioned Japanese macaque troops. Although the exact cause of this problem was not determined, the occurrence of malformations decreased thereafter. We examined possible factors such as total population size, number of adult females, birth rate, and volume of provisioned food. Agrichemicals attached to provisioned food are suspected as the main cause, as other factors were found to have no influence. Many more malformations were seen in males compared with females, in feet compared with hands, and in the fourth compared with other digits. We confirmed that the frequency of congenital malformation was high during the 1960s through to the mid-1970s when increased levels of provisioned food were given and that the incidence of congenital malformations was also elevated among wild macaques during this time.     

Classification of the abnormality concept

This paper deals with congenital malformations in man and presents a classificatory system for them. It first distinguishes abnormalities from normal variation and then further separates between primary and secondary structural disorders. Secondary disorders are those which are due to disturbances in primary normal tissues. Every maldevelopment which originates in prenatal life, is a congenital malformation. The level at which the malformation occurs must be considered, i. e. whether it is at the organism level, organ level, tissue, cell or subcellular level. A standardized system is absolutely necessary if the incidence of malformations is to be compared throughout the world.     

In vitro fertilization (IVF) in Sweden: risk for congenital malformations after different IVF methods

BACKGROUND: The possible excess of congenital malformations in infants born after in vitro fertilization (IVF) has been much discussed in the literature, with controversial conclusions. This population based study is aimed at analyzing the presence of congenital malformations in a large group of infants born after IVF and to compare malformation risk both with that of all infants born and according to IVF method used. METHODS: Infants born after IVF during the period 1982-2001 were ascertained from all IVF clinics in Sweden. The presence of congenital malformations was identified from three national health registers: the Swedish Medical Birth Register, the Swedish Registry of Congenital Malformations, and the Swedish Hospital Discharge Register. The IVF children were compared with all children born in Sweden during the same period and recorded in the Swedish Medical Birth Register. RESULTS: Among 16,280 IVF children (30% conceived after intracytoplasmatic sperm injection [ICSI]) a 42% excess of any congenital malformation was found, explainable by parental characteristics and in some cases by the high rate of multiple births. Among these children, 8% had a congenital malformation, and 5% had a relatively severe condition. For neural tube defects, choanal atresia, and alimentary tract atresia, an additional risk increase was seen. There was no difference in malformation rate according to IVF method except for an excess of hypospadias after ICSI. CONCLUSIONS: An increased risk for congenital malformations occurs after IVF, similar for the different IVF techniques used, and mainly a consequence of parental characteristics. A few specific conditions show an extra increase in risk.     

When hormone defects cannot explain it: Malformative disorders of sex development

The birth of a baby with malformations of the genitalia urges medical action. Even in cases where the condition is not life‐threatening, the identification of the external genitalia as male or female is emotionally essential for the family, and genital malformations represent one of the most stressful situations around a newborn. The female or male configuration of the genitalia normally evolves during fetal life according to the genetic, gonadal, and hormonal sex. Disorders of sex development occur when male hormone (androgens and anti‐Müllerian hormone) secretion or action is insufficient in the 46,XY fetus or when there is an androgen excess in the 46,XX fetus. However, sex hormone defects during fetal development cannot explain all congenital malformations of the reproductive tract. This review is focused on those congenital conditions in which gonadal function and sex hormone target organ sensitivity are normal and, therefore, not responsible for the genital malformation. Furthermore, because the reproductive and urinary systems share many common pathways in embryo‐fetal development, conditions associating urogenital malformations are discussed. Birth Defects Research (Part C) 102:359–373, 2014. © 2014 Wiley Periodicals, Inc.     

A familial tetraphocomelia syndrome involving limb deformities,cleft lip,cleft palate,and associated anomalies —A new syndrome

Summary This paper reports a rare malformation syndrome which is observed in two sibs (brother and sister) of a family. It consists of nearly symmetric reductive defects of the limbs, flexon contractures of various joints, cleft lip and cleft palate, multiple minor abnormalities including capillary hemangioma of the forehead, hypoplastic cartilages of ears and nose, micrognathia, intrauterine growth retardation, and possibly mental retardation. Chromosomes of both parents and propositi are normal. Genetic data suggest autosomal recessive inheritance.     

Trps1 is necessary for normal temporomandibular joint development

Mutation of the human TRPS1 gene leads to trichorhinophalangeal syndrome (TRPS), which is characterized by an abnormal development of various organs including the craniofacial skeleton. Trps1 has recently been shown to be expressed in the jaw joints of zebrafish; however, whether Trps1 is expressed in the mammalian temporomandibular joint (TMJ), or whether it is necessary for TMJ development is unknown. We have analyzed (1) the expression pattern of Trps1 during TMJ development in mice and (2) TMJ development in Trps1 knockout animals. Trps1 is expressed in the maxillo-mandibular junction at embryonic day (E) 11.5. At E15.5, expression is restricted to the developing condylar cartilage and to the surrounding joint disc progenitor cells. In Trps1 knockout mice, the glenoid fossa of the temporal bone forms relatively normally but the condylar process is extremely small and the joint disc and cavities do not develop. The initiation of condyle formation is slightly delayed in the mutants at E14.5; however, at E18.5, the flattened chondrocyte layer is narrowed and most of the condylar chondrocytes exhibit precocious chondrocyte maturation. Expression of Runx2 and its target genes is expanded toward the condylar apex in the mutants. These observations underscore the indispensable role played by Trps1 in normal TMJ development in supporting the differentiation of disc and synoviocyte progenitor cells and in coordinating condylar chondrocyte differentiation.     

Apple Down 152: A putative case of syphilis from sixth century AD Anglo‐Saxon England

This report describes a putative case of a treponemal infection observed on a skeleton of a young male adult from the Apple Down Anglo‐Saxon cemetery dating to the sixth century AD, accompanied by grave goods indicative of a high status burial. The skeleton is well preserved and almost complete. The pathological evidence includes an extensive area of lytic destruction to the frontal bone of the skull, widespread profuse bilateral symmetrical periosteal reaction affecting scapulae, clavicles, arms, legs, hands, feet and ribs. There is also evidence of gummatous destruction on some of the long bones. Application of a differential diagnosis of all probable diseases exhibiting the individual symptoms leads to a clear conclusion that the person was infected with a treponemal pathogen. The skeleton shows none of the stigmata associated with the congenital form of treponemal disease. We propose that the evidence suggests a possible case of venereal syphilis rather than one of the endemic forms of treponemal disease. This diagnosis is based on the geographical pathogen range, the apparent low prevalence of the disease, significant social upheaval at the time, the high social status and early age of death of the individual. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc.     

Morphological observations on the congenital malformation of limbs in the Japanese monkey

Congenital malformation of limbs is found in many troops of the Japanese monkey. The author morphologically examined more than ten monkeys with such malformations by means of palpation and Röntgenographing. Anatomical dissection was performed on two of these monkeys. Malformation manifests a considerable variety of forms, from the reduction or absence of fingers to almost total lack of limbs, and is prone to occur in the region of the third finger, the center of malformation, occasionally showing a “split” or “cleft” hand or foot. The latter tendency is more conspicuous in the hand than in the foot. In a word, most of the malformations are characterized by congenital amputation, though the degree varies considerably. The occurrence of supernumerary digits was not found and fusion between fingers was rare. One of the most interesting anatomical results found may be the continuation or fusion between muscles which are normally opposed to each other in action. The occurrence of malformation is more frequent in the male than in the female, and in the hand than in the foot. Little is known about the causes of such malformations, except that they do not occur, at least, according to dominant inheritance.     

A prehistoric example of polydactyly from the Iron Age site of Simbusenga, Zambia

Human burials, dated AD 1100-1500, were examined from the Iron Age site of Simbusenga, located some 35 miles northwest of Victoria Falls in Zambia. Pedal polydactyly was discovered in the fragmentary remains of a young adult of indeterminate sex aged 14-25. The preaxial form of polydactyly is indicated with bilateral involvement of the first metatarsals. There is incomplete hypoplastic duplication of both first metatarsals with broad heads for the metatarsal-phalangeal joints. No digital malformations were found in the other seven individuals with feet and/or hands from the site. Several studies point to autosomal dominance for cases of isolated polydactyly, but inheritance and patterning of preaxial polydactyly are still incompletely understood. The condition is also found in conjunction with genetic malformation syndromes such as Acrocephalypolysyndactyly, Lambotte, Oro-facio-digital, and VATER. High frequencies of polydactyly are reported for African and African-American populations, but further analysis reveals that the bulk of previously reported cases of polydactyly are representative of the postaxial form as opposed to the preaxial expression seen here.     

Paleoepidemiology of a central California prehistoric population from Ca-Ala-329: II. Degenerative disease

Degenerative lesions are scored and frequencies of involvement are computed for a skeletal collection from Ca-Ala-329, a prehistoric site on the southeastern side of San Francisco Bay, dating from 500 A.D. up to European contact. A large earthmound site, excavations conducted there by San Jose State University retrieved close to 300 burials. For this epidemiological analysis, reasonably complete and aged skeletons representing 77 adult females and 90 adult males are available. Degenerative changes are scored macroscopically in an ordinal fashion for the large fibro-cartilagenous joints between adjacent vertebral bodies (vertebral osteophytosis) as well as the small apophyseal articulations of the spine. In addition, in the peripheral skeleton degenerative changes are scored in the temporo-mandibular, shoulder, elbow, hip, and knee joints as well as the small articulations of the hands and feet. The most common degenerative changes in the spine are seen between the vertebral bodies of the lower lumbar region. In the peripheral skeleton the highest involvement of degenerative disease is seen in the hands and feet. Compared to other relevant osteological samples, this group of hunting-gathering California Indians shows more degenerative changes than settled agriculturists (from Pecos Pueblo, New Mexico) but substantially less frequent involvement than in arctic hunters (Alaskan Eskimos).     

Anophthalmos with limb anomalies (Waardenburg opththalmo-acromelic syndrome): report of a new Italian case with renal anomaly and review

Anophthalmos with limb anomalies (Waardenburg Opththalmo-Acromelic Syndrome) is a very rare autosomal recessive multiple congenital anomaly syndrome, first described by Waardenburg et al. in 1961 (MIM 206920). It is characterized by mono or more often bilateral anophthalmia/microphthalmia and foot malformations, which can be observed in 91% of the patients. The most common anomaly of the feet is the presence of four toes. The hands are affected bilaterally in 77% of the cases. The most characteristic anomaly is the synostosis of the fourth and fifth metacarpals. To date, 33 cases from 19 families have been reported. We present an Italian case of anophthalmia with limb anomalies and a renal malformation, which has never been described in the literature.     

Associated malformations in cases with congenital diaphragmatic hernia

The etiology of congenital diaphragmatic hernia (CDH) is unclear and its pathogenesis is controversial. Because previous reports have inconsistently noted the type and frequency of malformations associated with CDH, we assessed these associated malformations ascertained between 1979 and 2003 in 334,262 consecutive births. Of the 115 patients with the most common type of CDH, the posterolateral, or Bochdalek-type hernia, 70 (60.8%) had associated malformations. These included: chromosomal abnormalities (n = 21, 30.0%); non-chromosomal syndromes (Fryns syndrome, fetal alcohol syndrome, De Lange syndrome, CHARGE syndrome, Fraser syndrome, Goldenhar syndrome, Smith-Lemli-Opitz syndrome, multiple pterygium syndrome, Noonan syndrome, and spondylocostal dysostosis); malformation sequences (laterality sequence, ectopia cordis); malformation complexes (limb body wall complex) and non syndromic multiple congenital anomalies (MCA) (n = 30, 42.9%). Malformations of the cardiovascular system (n = 42, 27.5%), urogenital system (n = 27, 17.7%), musculoskeletal system (n = 24, 15.7%), and central nervous system (n = 15, 9.8%) were the most common other congenital malformations. We observed specific patterns of malformations associated with CDH which emphasizes the need to evaluate all patients with CDH for possible associated malformations. Geneticists and pediatricians should be aware that the malformations associated with CDH can often be classified into a recognizable malformation syndrome or pattern (57.1%).     

Fallot's tetralogy in a European brown bear (Ursus arctos)

A congenital heart malformation was diagnosed in a free-ranging adult female European brown bear (Ursus arctos) found dead due to intraspecific violence. At necropsy, the heart had all four features of Fallot's tetralogy. No further malformations were identified in the animal, which was of normal size and weight for its age, in normal body condition, and had probably borne young. The heart condition was considered to have contributed to death during an attack by another bear.     

CHARGE Association in newborns: a registry-based study

The CHARGE Association is a nonrandom occurrence of congenital malformations that has been described in clinical series. Reported patients have been selected on the basis of certain prior criteria. In this article, we try to identify a congenital malformation pattern corresponding to the CHARGE Association, using statistical methods and analyzing 5,260 infants with multiple malformations collected from four large registries of congenital malformations. Care was taken to identify a number of confounding characteristics that can influence the ascertainment and registration of specific congenital malformations. We have identified a cluster of malformations that generally agreed with the current clinical definition of the CHARGE Association and have added some further malformations (e.g., facial clefts). We demonstrate that others (e.g. , esophageal atresia) are probably not part of the pattern. Heart defects (H in the acronym) seems to be less helpful in identifying infants with the association. We suggest a method to select infants who probably represent the CHARGE Association for analyses of possible risk factors.     

二噁英致大鼠先天骨骼发育畸形中软骨细胞的病理学改变

目的探讨大鼠骨骼发育过程中环境类致畸因子对大鼠骨骼发育的先天性致畸作用。方法应用不同剂量的环境类致畸因子-二噁英（2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD）构建先天性Wistar大鼠骨骼发育畸形动物模型;茜素红染色法制作并观察透明骨骼标本;采用光镜和透射电镜观察胎鼠趾骨骨化中心的软骨细胞病理学变化及细胞超微结构的改变。结果TCDD在5～15μg／kg浓度下诱导了大鼠骨骼发育畸形,畸形包括：内翻足、脊柱裂、腭裂、无尾畸形等,并存在剂量依赖性生物学效应;光镜下可见在畸形胎鼠的肢端骨化中心软骨发生带缩小,软骨细胞变性。透射扫描电镜下见软骨细胞核内粗面内质网扩张,核基质降解,线粒体嵴不规则。结论在高雌激素水平下,TCDD可以诱导大鼠骨骼发育畸形;TCDD可能通过干扰软骨细胞的形态和功能代谢,引起原发性骨化中心的结构紊乱而发挥骨骼致畸效应。     

Early fetal growth delay detected by ultrasound marks increased risk of congenital malformation in diabetic pregnancy.

Ninety-nine insulin-dependent diabetic women with regular menstrual histories were examined by ultrasonic scanning in the seventh to 14th weeks of pregnancy. As judged by the crown-rump length 38 fetuses were smaller than normal. The term early growth delay is suggested for this phenomenon. Nine fetuses had major congenital malformations, and seven of them were smaller than normal in early pregnancy (p less than 0.02). The risk of fetal malformation in diabetic pregnancy increases with the severity of the diabetes. Early fetal growth delay is apparently another risk marker, in this series indicating a risk of 18% (7/38). The combination of severe maternal diabetes (White''s classes D and F) and early growth delay yielded a risk of major congenital malformation of 27% (6/22). These observations suggest a common mechanism behind early growth delay and induction of abnormal embryogenesis (and maybe even fetal death). The mechanism is unknown but probably influenced by the quality of regulation of diabetes.     

Bias in congenital malformations information from the birth certificate

An analysis of 1983 data from California birth certificates, and from the California Birth Defects Monitoring Program case registry, showed that there is a bias in reporting of congenital malformations on the birth certificate. Hospitals with many births erroneously report lower malformation rates than do hospitals with few births. The bias is partly due to the source of information; larger hospitals are more likely to get their information about malformations from the obstetrician than from the pediatrician. Since malformation data recorded on the birth certificate is both incomplete and biased, at present it is advisable to use these data for epidemiologic analyses with great caution.     

The frequency of genetic disease and congenital malformation among patients in a pediatric hospital

A sample of 12,801 admissions to a pediatric hospital was surveyed in 1969-70 to determine the prevalence of disease which could be classified as “genetic” in origin or related to “congenital malformation”.“Genetic” admissions accounted for 11.1% of the total while 18.5% were for congenital malformations; about 2% (unknown group) were probably genetic. Therefore about one third of all admissions represent the effect of abnormal gene-environment interrelations at some point in the development or life of the patient.The “genetic” patient is admitted more often to a medical service while the patient with congenital malformation usually goes to a surgical service; the former stays 7.3 days and the latter 8.6 days. A disproportionate number of patients staying longer than 10 days were found in the group with congenital malformations. Seventy percent of the patients with multiple admissions (3.2% of all admissions) have genetic illness or congenital malformation.