Costello syndrome: phenotype, natural history, differential diagnosis, and possible cause.

We describe 8 patients affected with Costello syndrome including an affected sib pair and review the literature on 29 previously reported cases. We emphasize an association with advanced parental age, which is consistent with autosomal dominant inheritance with germline mosaicism. The pathogenesis appears to involve metabolic dysfunction, with growth disturbance, storage disorder appearance, acanthosis nigricans, hypertrophic cardiomyopathy, and occasional abnormalities of glucose metabolism. Although the cause is currently unknown, Costello syndrome is interesting because of a potential genetic-metabolic etiology.

The face of Job.

We evaluated facial features in 9 patients from 7 kindreds with Job syndrome. Consistent features included prominent forehead with deep-set eyes, increased width of the nose, a full lower lip, and thickening of the nose and ears. The mean alar width (Z score = +3.9) and outer canthal distance (Z score = +2.2) were significantly increased. A recognizable face of Job syndrome exists.

Socioeconomic change and patterns of growth in the Andes.

Changes in the pattern of growth over a 20-year period are described for a combined rural and semi-urban population in the District of Nuñoa (Puno) in southern Peruvian Andes. Over the past two decades, Andean regions have experienced many socioeconomic changes, including the implementation of agrarian reform policies and increased integration into a market economy. Local changes in Nuñoa have included improved transportation networks, new markets, an expanded public school system, and improved health care facilities. Secular trends in stature and weight have been found to be associated with social and economic development throughout the developing world, including Peru. The purpose of this paper is to present the findings from a re-study of growth in the Nuñoan population, and to assess whether changing conditions in Nuñoa have resulted in secular increases in growth. A cross-sectional sample of 1,466 children and adults and mixed-longitudinal sample of 404 children (age 3-22), measured between 1983 and 1984, are compared to similar samples collected from the same location between 1964 and 1966. Adolescents are taller, heavier, and somewhat fatter in the present population, although these differences diminish or disappear in adulthood. Age of maturation, peak growth velocities, and cessation of growth may come 1 to 2 years earlier than in the 1960s. As was found in earlier studies, growth velocities are low, the adolescent growth spurt is small, and sexual dimorphism is delayed. No secular trends in adult stature were found. Thus, the effects of social and economic change on nutrition, health, and growth in the population are uneven and generally unclear. This points to inequalities in access to the benefits of change throughout the region.

Urethral obstruction sequence and lower limb deficiency: evidence for the vascular disruption hypothesis.

We reviewed five unreported examples and 23 previously reported cases of urethral obstruction sequence with associated lower limb deficiency. There was no evidence of amniotic bands or exposure to vasoactive drugs during pregnancy in any case. In three infants a gangrenous lesion at the distal part of the affected leg was found; in another three infants, necrotic tissue was noted in the stump of the affected leg. This type of lesion can be explained only on a vascular ischemic basis. In five cases, signs of compression of the external iliac artery by the grossly distended bladder, by grossly distended ureters, or both were found. A vascular disruption in the territory of the external iliac artery caused by compression by the distended urinary tract is the proposed mechanism for the associated limb deficiency.

The ethnographic context of illness among single-women-headed households in rural Peru.

Peru is undergoing many deleterious economic and social changes, and the health consequences for families headed by single women is of special concern. However, not all single mothers' families may be at similar risk of morbidity. My purpose in the present study was to determine whether variation in illness prevalence was associated with ostensibly small differences in socioeconomic resources and physical living conditions in areas like Peru. I used both qualitative and quantitative methods in this study. The sample included single-women-headed households from the rural Nuñoa District, located in the southern Peruvian Andes (N = 22 families with 90 individuals). Quantitative cross-sectional survey results suggested that the mother's formal education, the availability of a latrine, drinking water contamination, the gender ratio of the household, and the quality of the social support network were key risk factors. They statistically predicted 35-91% of the morbidity variance between families (p < or = .03-.0001). I illustrate these findings in three ethnographic case studies. The case studies show how the degree of illness among single-women-headed families was affected by small differences in their social and physical living conditions.

PIP: The purpose of this study was to determine whether illness prevalence was associated with small differences in socioeconomic and living conditions in the Nunoa District of Peru where 9800 people lived. Between 1960 and 1984, the average annual infant mortality rate was 134.8 deaths/1000 live births. The focus was on single mothers and their families in the town of Nunoa and in a clan village called Sincata. In the town, mean household size was 5.2 (SD=1.9) persons. In Sincata, families were smaller, with an average of 4.9 (SD=2.3) persons. Single women generally had smaller families. Formal education for adults in the town averaged 6.4 (SD=2.4) years. Adults in Sincata had only 3.8 (SD=2.3) years of education. Representative Nunoa (n=96 families, totaling 371 persons) and Sincata (n=25 families, totaling 110 persons) samples were obtained. Of the 121 households, 22 were headed by single mothers. The structured interview responses regarding individual illnesses, demographic characteristics, socioeconomic circumstances, and physical living conditions were analyzed by correlation and multiple regression statistics. The use of a latrine, the level of the mother's formal education, the source of drinking water, and the household sex ratio together predicted 91% of the variance in reported symptom levels. Illness duration was correlated with mother's education (p=.0007). Mother's education also was connected to a disruptive effect of illness on work (p.0014). Variance in household child stature for age was strongly predicted by drinking water source and social support network quality (p0014). Water source alone predicted 35% of weight-for-age variance (p=.03). The social resources of the mother and the physical living conditions statistically predicted 35-91% of the morbidity variance among single-women-headed families (p=.03-.0001). These findings are illustrated in three ethnographic case studies.

Development of human palmar and digital flexion creases.

To determine the timing of the development of the various palmar and digital creases, we examined the hands of 100 human fetuses obtained after therapeutic abortion. The fetuses ranged in age from 7 to 19 fetal weeks, with age being established by menstrual period dates and ultrasound examination before termination. Our observations show that palmar and digital creases develop between 8 and 13 fetal weeks. Digital creases are well defined by 10 weeks; palmar creases are consistently seen by 13 weeks of gestation. The volar pads are present from 8 to 14 fetal weeks. A hand malformation or specific insult that occurs before the time of crease development and that alters the form or function of the fetal hand can cause secondary alterations increase patterns of the hand.

Femoral hypoplasia-unusual facies syndrome in infants of diabetic mothers.

Three children with the femoral hypoplasia-unusual facies syndrome are described. Two had the characteristic facial pattern of upslanted palpebral fissures, long philtrum with thin upper lip, micrognathia, and hypoplastic alae nasi. The other, an infant girl who died within 24 hours after birth, had a cleft lip, which distorted some of the other features. She also had a cleft palate, as did one of the two older boys. All three children had ear defects, upper limb involvement, and rib, vertebral, lower extremity, and genitourinary tract abnormalities. The infant girl died of lung hypoplasia associated with dysplastic kidneys and widely patent ductus arteriosus. All three were infants of diabetic mothers, one mother having developed overt diabetes in the first trimester of pregnancy. A literature review of 36 reported cases of FH/UFS revealed 12 individuals who were IDMs, establishing a strong relationship of the syndrome with maternal diabetes. A multifactorial inheritance model fits with the reported patients, with the relationship to diabetes, and with the similarity of FH/UFS to caudal regression, another condition related to maternal diabetes.

The Robin sequence as a consequence of malformation, dysplasia, and neuromuscular syndromes.

The Robin sequence is a pathogenetically and etiologically heterogeneous conditions that can be an isolated defect or one feature of many different syndromes. The association of this pattern of malformation with neuromuscular conditions has been alluded to in the literature but not well documented. We report a family with a distinct neuromuscular condition that includes the Robin sequence and discuss the human syndromes and animal models in which the Robin sequence occurs.

Confirmation of the Cohen syndrome.

In 1973 Cohen et al reported a new syndrome in two siblings and an unrelated individual, consisting of obesity, mental retardation, hypotonia, limb abnormalities, and a characteristic craniofacial appearance. Since then no similar cases have appeared in the literature. This report firmly establishes the Cohen syndrome as a distinct clinical entity by presenting four additional patients, including a sibling pair of normal parents, suggesting autosomal recessive inheritance. One of our four patients has normal intelligence, indicating that mental deficiency is a variable feature of the syndrome.