Search

ObjectivesWomen with Turner syndrome (TS) are frequently counselled against pregnancy due to lack of data and unclear aortic dissection risk. However, with advances in fertility therapy, more women with TS are contemplating pregnancy. This study compared rates of adverse cardiovascular (CV) outcomes among: (1) pregnant and non-pregnant women with TS and (2) pregnant women with TS with/without structural heart disease.MethodsRetrospective analysis of pregnant and age-matched non-pregnant controls with TS (2005–2017) across 10 CV centres was done. Data were collected at initial evaluation in pregnancy and outcomes were assessed to 6 months postpartum. Adverse CV events were defined as CV death, aortic dissection/rupture and/or aortic intervention. Non-pregnant age-matched controls were followed over the same time period.ResultsSixty-eight pregnancies were included (60 women, mean age 33 years, 48% primigravid, 49% fertility therapy, 80% structurally normal heart, 25% XO karyotype). Based on American Society of Reproductive Medicine criteria, 10 pregnancies occurred in women stratified to high-risk category. There were no CV events in the pregnant women or in the non-pregnant women with TS. Obstetric events complicated 12 (18%) pregnancies with 9 (13%) attributed to hypertensive disorder of pregnancy. Fetal events included small for gestational age neonates (18%), preterm delivery (15%) and fetal death (3%).ConclusionsThis study helps to refine the approach to pregnancy in women with TS. Among women with TS without structural heart disease, pregnancy does not impose an increased risk of CV outcomes. Among women with TS with structural heart disease, the risk of pregnancy is not as prohibitive as previously described but does require ongoing evaluation.

High quality information is critical for informed decision-making in pregnancy following a prenatal diagnosis of sex chromosome aneuploidy. The goal of this study was to define the spectrum of outcomes in patients with prenatally diagnosed 45,X/46,XX mosaic Turner syndrome in order to provide a better basis for genetic counseling at the time of intrauterine diagnosis. Phenotype data for twenty-five patients with prenatally diagnosed 45,X/46,XX mosaicism were collected by retrospective chart review and, when possible, semi-structured telephone interview. Existing data from a cohort of 58 patients with postnatally diagnosed 45,X/46,XX mosaicism were used for comparison. Relative to those diagnosed postnatally, prenatal patients were more likely to have normal growth and normal secondary sexual development, less likely to manifest distinctive Turner syndrome features such as nuchal webbing and edema, and had significantly fewer renal defects. These differences underscore the need for a nuanced approach to prenatal counseling in cases of 45,X/46,XX mosaicism.

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome (Hay-Wells syndrome, MIM #106220) is a rare autosomal dominant ectodermal dysplasia syndrome. It is due to mutations in the TP63 gene, known to be a regulatory gene with many downstream gene targets. TP63 is important in the differentiation and proliferation of the epidermis, as well as many other processes including limb and facial development. It is also known that mutations in TP63 lead to skin erosions. These erosions, especially on the scalp, are defining features of AEC syndrome and cause significant morbidity and mortality in these patients. It was this fact that led to the 2003 AEC Skin Erosion Workshop. That conference laid the groundwork for the International Research Symposium for AEC Syndrome held at Texas Children's Hospital in 2006. The conference brought together the largest cohort of individuals with AEC syndrome, along with a multitude of physicians and scientists. The overarching goals were to define the clinical and pathologic findings for improved diagnostic criteria, to obtain tissue samples for further study and to define future research directions. The symposium was successful in accomplishing these aims as detailed in this conference report. Following our report, we also present 11 manuscripts within this special section that outline the collective clinical, pathologic, and mutational data from 18 individuals enrolled in the concurrent Baylor College of Medicine IRB-approved protocol: Characterization of AEC syndrome. These collaborative findings will hopefully provide a stepping-stone to future translational projects of TP63 and TP63-related syndromes.

A medical genetics clinic is a unique and complex environment in which care requires a combination of medical knowledge, social intelligence, and emotional sensitivity. We offer a few pearls from our medical genetics clinic that we hope will help the pediatric or general dermatologist when caring for patients with known or suspected genetic disorders. This paper addresses five main topics: When is it more than just atopic dermatitis? How should the clinician approach blistering in the newborn period? What is mosaicism? When is genetic testing useful? Where can clinician, patients, and families turn for available resources?

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine.

This article contains the author's views on genetic counseling in cases concerning the epidermolysis bullosa syndromes. The provision of genetic counseling entails absolutes such as diagnosis, natural history, treatment, mode of inheritance, recurrence risks/prenatal diagnosis and referral. The genetic counselor needs to be informed and informative and answer all the needs of the patients and their families reliably both at the initial consultation and subsequently as needed over the course of the patient's life.

Variable expression and penetrance of dominantly inherited disorders present problems in diagnosis and counseling. The variation in clinical findings within a family with an autosomal dominant skeletal dysplasia is presented. In some members only shortened metacarpals were found, as seen in classic Brachydactyly E. Others presented with more severe and generalized skeletal involvement, such as is found in some of the spondyloepiphyseal dysplasias. This family may represent the true spectrum of Brachydactyly E; they may be affected with a specific spondyloepiphyseal dysplasia; or they may represent a new syndrome. The authors favor the first possibility and feel that this family serves to emphasize the importance of examining all affected members in a kindred with an autosomal dominant disease.

Holt-Oram syndrome is an autosomal dominant disorder with variable expression. From a review of published pedigree data and of a family reported here, we have found that penetrance is 100 % if appropriate studies, including wrist radiographs, are performed. There does not appear to be a significant maternal effect on the severity of expression in affected offspring.

Turner syndrome is a chromosomal disorder due to an absent or abnormal X chromosome. The two most typical features are short stature and gonadal dysgenesis. There is a wide range of other phenotypic features, many of which are thought secondary to lymphedema during embryogenesis. Reviewed are common sequelae of lymphatic obstruction, as well as common tooth and skin findings.

We describe a family with woolly hair and ulerythema ophryogenes spanning four generations. Both woolly hair and ulerythema ophryogenes have been associated with Noonan syndrome and cardiofaciocutaneous syndrome (CFC), two disorders with considerable phenotypic overlap. This family did not exhibit any of the other findings characteristic of either Noonan syndrome or CFC, similar to a previously described pedigree with hereditary woolly hair. Woolly hair elicits a broad differential diagnosis, including woolly hair nevus and several genodermatoses. Our report reviews the evaluation of woolly hair and discusses the conditions associated with this physical finding.

Areas of blanched skin in children may be seen as an independent finding or in association with vascular birthmarks. We performed a retrospective chart review to identify and describe infants with areas of ventral midline blanching in the presence of segmental infantile hemangiomas. We identified nine full-term infants with partial or full segmental hemangiomas and areas of midline ventral blanching. Additional ventral wall defects were seen in five patients. Six had cardiac anomalies and six had intracranial anomalies. Five were diagnosed with definite PHACE (posterior fossa, hemangioma, arterial, cardiac, and eye abnormalities) syndrome and three had possible PHACE syndrome. Eight were complicated by ulceration. Treatment varied according to the case. Ventral blanching, even in the absence of overt midline defects, can be seen in infants with segmental hemangiomas at risk for PHACE syndrome. We hypothesize that midline blanching may represent a minor manifestation of a developmental ventral defect.

Purpose of reviewThis article reviews the disorders of patterned dyspigmentation and discusses the pathogenesis of the pigmentary changes.Recent findingsA range of cytogenetic abnormalities has been detected in patterned pigmentary disease. This molecular heterogeneity correlates with the wide spect

Malignant melanoma is rare in childhood and has never been reported to cause pancytopenia due to bone marrow metastases in a child. We report a 3-year-old boy with a large congenital melanocytic nevus who presented with bone pain and pancytopenia due to diffuse bone and bone marrow infiltration with metastatic melanoma without an identifiable primary site. Despite treatment with imatinib mesylate there was no response and the patient died with progressive disease. This case illustrates an unusual presentation of bone marrow failure secondary to malignant melanoma in a young child with symptomatic metastatic marrow infiltration, a rarely reported site of melanoma involvement in adults or children.

The field of pediatric dermatology continues to be enriched by the insights offered through molecular genetics. For some genetic skin disorders, including neurofibromatosis, tuberous sclerosis complex, and several forms of epidermolysis bullosa, genetic research has resulted in an evolving understanding of the relationship between genotype and phenotype, with the ability to predict some of the features of these disorders on the basis of the genetic defect. However, widespread use of molecular genetics for diagnostic testing of these disorders has not been possible because of genetic heterogeneity, limited availability, and reduced sensitivity. The appropriate use of genetic services is emphasized in this, the molecular era.

Two brothers demonstrated a severe variant of trichothiodystrophy. Both had brittle hair, developmental delay with severe failure to thrive, recurrent infections, cataracts, and angioendotheliomas of the liver at autopsy. The elder died at 12 weeks, the younger at 6 months. The younger had the typical appearance of banded hair on polarizing microscopy and a low cystine content measured by ion exchange chromatography. The history, clinical findings, and basic defects of trichothiodystrophy are discussed.

Hay-Wells syndrome is an autosomal dominant condition characterized by ankyloblepharon filiforme adnatum, ectodermal dysplasia, and cleft palate with or without associated cleft lip (AEC syndrome). Although several reported patients had eroded skin at birth and recurrent scalp infections, these are not generally regarded as major features of the disorder. In our experience, denuded skin at birth and chronic scalp erosions complicated by infection are common features of this syndrome. Aggressive wound care in conjunction with early administration of topical or systemic antibiotics is suggested.

We report on the prenatal diagnosis of epidermolysis bullosa letalis with pyloric atresia in a pregnancy not known to be at risk for this condition. Elevated maternal serum alpha-fetoprotein levels led to ultrasonography which demonstrated gastric dilatation, consistent with pyloric atresia, and echogenic particles in the amniotic fluid, the "snowflake sign," previously described in two pregnancies of fetuses with disorders of skin sloughing. Amniotic fluid alpha-fetoprotein was markedly elevated and the acetylcholinesterase was positive. The diagnosis of epidermolysis bullosa letalis with pyloric atresia was confirmed after delivery by electron microscopy of fetal skin which showed typical changes of hypoplastic absent hemidesmosomes and separation along the dermal-epidermal junction. None of these abnormal prenatal findings are consistently present in pregnancies with epidermolysis bullosa with pyloric atresia. Thus, although useful when abnormal, when the test results are normal, the need for confirmatory fetoscopy and fetal skin biopsy remains.

Background Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by tumors and hamartomas in several organs including the skin. Objective We sought to describe a new type of complex hamartoma in patients with TSC. Methods This was a retrospective clinical and histopathologic evaluation of 6 cases. Results The skin lesions consisted of large, painless, infiltrated plaques that were first noticed at birth or during early infancy on the abdomen, thigh, back, or scalp. In time, the plaques became studded with numerous follicular comedo-like openings and cysts containing and draining a keratinous or purulent material. The main histopathologic features were: abundant collagen deposition in the dermis and extending into the underlying fat; concentric, perifollicular fibrosis surrounding hair follicles; and comedones and keratin-containing cysts lined by infundibular epithelium, some of which were ruptured with secondary granulomatous reaction. Five of the 6 patients had a clinical diagnosis of TSC. Limitations Genetic testing was performed in only one patient. Conclusion This distinctive folliculocystic and collagen hamartoma has not been recognized previously in association with TSC.

Inherited epidermolysis bullosa encompasses a number of diseases, with the common finding of blister formation, after minor mechanical trauma to the skin. In some forms significant, if not eventually fatal, extracutaneous disease activity may occur. In recent years application of newer technologies has contributed substantially to an overall understanding of this collection of inherited diseases. Concurrently, many new phenotypes have been recognized, in part the result of ongoing prospective patient registries in the United States and abroad. Unfortunately, this has resulted in a massive literature that may appear to be confounded by seemingly excessive or arbitrary subdivision of epidermolysis bullosa variants. With these concerns in mind a subcommittee was established by the National Epidermolysis Bullosa Registry to summarize the current literature and to make recommendations as to the best clinical and laboratory criteria for the practical diagnosis and subclassification of patients with inherited epidermolysis bullosa.

Objective.Clinical observations suggested that growth abnormalities may be present in children with ectodermal dysplasia (ED) syndromes. This study characterizes the longitudinal pattern of growth in a cohort of children with the ED syndromes. We hypothesized that (1) linear and ponderal growth abnormalities are present in children with ED from infancy through adolescence, and (2) linear and ponderal growth abnormalities differ among the clinical variants of these disorders.Methods.We studied 138 children who had ED and were registered with the National Foundation for Ectodermal Dysplasias, 74% of whom had clinical features consistent with the hypohidrotic EDs (HEDs). Height (or length) and weight measurements were obtained by standardized techniques and from review of available medical records. We converted these measurements to weight-for-height (children younger than 5 years and Results.Mean weight-for-age, weight-for-height, and BMI-for-age z scores but not height-for-age z score, were significantly lower in children with the ED syndromes than in the reference population. Mean weight-for-age and weight-for-height z scores but not BMI-for-age or height-for-age z scores increased significantly with increasing age. The mean height-for-age z score of children with the ED syndromes other than the HEDs was significantly lower than that of children with the HEDs.Conclusions.Growth abnormalities, measured as weight deficits, were present at an early age in children with the ED syndromes and persisted through adolescence. Height deficits were seen only in children with ED syndromes other than HEDs. Clinicians should evaluate carefully children with ED syndromes for growth abnormalities.

Although most children with Turner's syndrome are under the care of specialists, the authors of this article suggest that most affected women can best be served by their primary care practitioners, with the use of informed judgment about the need for referral to specialists. This article reviews current concepts in the genetics, diagnosis, and management of Turner's syndrome.

Purpose: To determine whether pregnancy increases the risk of renal or pulmonary complications in women with tuberous sclerosis complex (TSC). Methods: We surveyed female members of the Tuberous Sclerosis Alliance and reviewed the files of adult women seen in our genetics clinics for complications of TSC. Results: Among 145 individuals, there was no significant difference in incidence of renal and pulmonary involvement between the pregnant and never-pregnant groups, although there were differences in age at diagnosis (25 vs. 16) and current age (41 vs. 35). There was no significant difference in the rate of renal complications (57% vs. 67%, P = 0.62) or pneumothorax (40% vs. 38%, P = 1.00) for the pregnant and never-pregnant groups, respectively. Pregnancy loss in women with TSC did not differ from population risks. Conclusions: Pregnancy does not increase the risk of developing renal or pulmonary complications in women with TSC.

The goals of this study were to test the hypothesis that girls with Turner syndrome (TS) experience growth failure early in life and to establish model-based normative growth charts for 0- to 8-year-old American girls with TS. Full-term girls with TS who had 5 or more measurements of height obtained during their first 10 years of life prior to initiation of growth hormone, estrogen and/or androgen therapy were eligible for this study. A nonlinear mixed-effects model comprising the first two components of the infancy-childhood-puberty (ICP) model of growth was fitted to the longitudinal height measurements and compared with those of healthy American girls. Height measurements (n = 1,146) from 112 girls with TS (45,X: 57.1%; 45,X/46,XX: 12.5%; 46,X, iso(X): 4.5%, and other: 25.9%) were analyzed. Mean height SDS fell from –0.68 at birth to –1.60 at 1 year, –1.80 at 2 years and –1.95 at 3 years. When compared to controls (676 girls, 4,537 measurements), girls with TS grew more slowly due to three principal factors: a slow growth rate of the infancy component, a slow growth rate at the onset of the childhood component, and delayed onset of the childhood component. Traditional concepts of growth failure in TS should be revised. Physicians should consider the diagnosis of TS in any girl with unexplained failure to thrive or short stature, even in the first 3 years of life.

Background Junctional epidermolysis bullosa–pyloric atresia syndrome is recognized as a distinct autosomal recessive entity. Affected infants present with skin fragility and inability to feed due to intestinal obstruction. Despite successful surgical repair of the anatomical defect, the outcome is poor owing to poor feeding, malabsorption, failure to thrive, and sepsis. Observations In 70 cases of intestinal obstruction and epidermolysis bullosa reported in the medical literature and the 3 reported here, surgical intervention was attempted 51 times. In all except 16 infants, death occurred before age 11 months (mean age, 70 days). Renal involvement and continued failure to thrive accompanied the skin disease in survivors, who ranged in age from 30 days to 16 years (mean age, 4.0 years). Conclusions The poor prognosis of this condition must be considered when decisions are made regarding surgical correction. Attempting surgical correction may be warranted in individual circumstances, but withholding surgical intervention and providing palliative support is an acceptable alternative.

Unusual skin lesions were present at birth in four infants with Turner syndrome. The skin changes in these patients appear to have resulted either from in utero entrapment or pinching of edematous skin or from redundant skin remaining after in utero resolution of lymphedema. Distention by lymphedema is thought to cause several of the phenotypic characteristics seen in patients with Turner syndrome, including nuchal webbing and nail changes. In three of these patients the clinical appearance of the skin changes was similar to cutis verticis gyrata, marked by fixed thickened plaques in folds.

OBJECTIVE: Although hypopigmented macules are an important manifestation of tuberous sclerosis (TS), the probability of TS in healthy individuals who have hypopigmented macules is unknown. The purpose of this study was to establish the prevalence of hypopigmented macules among a cross section of the general white population. STUDY DESIGN: The skin of 423 white individuals younger than 45 years of age was screened for hypopigmented macules with ambient incandescent and fluorescent light and a Wood lamp. Indirect ophthalmoscopy was performed in patients with unexplained hypopigmentation to screen for retinal manifestations of TS. RESULTS: Twenty individuals (4.7%) had at least one hypopigmented macule. Of these, four had more than one macule. None had more than three. Two (8%) of the 25 hypopigmented macules were identified only with a Wood lamp. Indirect ophthalmoscopy was performed in 13 (65%) of these 20 individuals. None showed the retinal findings of TS. CONCLUSIONS: The prevalence of hypopigmented macules in the general population has been underestimated. The presence of a few hypopigmented macules on the skin of an otherwise healthy individual without a family history of TS need not prompt an evaluation to rule out this disorder. (J P EDIATR 1996;129:355-61)

Prenatal diagnosis of embryonic and fetal abnormalities is a multidisciplinary field of medicine whose techniques have been applied to an increasing number of inherited and sporadic disorders and malformations. Prenatal diagnosis for epidermolysis bullosa (EB) by fetoscopy was first reported in 1980.1 Since that initial report, numerous successful diagnoses and exclusions of EB in pregnancies at risk have been published.

Thirteen patients with hypopigmentation of the skin characteristic of hypomelanosis of Ito, and with developmental disabilities or structural malformations, or both, were examined at our center. Eight were found to have abnormal karyotypes in lymphocytes, fibroblasts, or both. No single clinical feature was predictive of chromosome imbalance in this group of patients. Cytogenetic findings included a balanced de novo X-autosome translocation; ring 10; 45,X/46,X,+ring; mosaic del 13q11 (fibroblasts); mosaic triploidy (fibroblasts); mosaic tetrasomy 12p (fibroblasts); mosaic apparently balanced 15;22 translocation (peripheral blood); and mosaic trisomy 18 (peripheral blood). Hypomelanosis of Ito is characterized by swirly hypopigmentation or depigmentation of the skin with or without other malformations. Autosomal dominant, autosomal recessive, and X-linked dominant inheritance have been suggested but not confirmed. Chromosomal aneuploidy has also been reported. We believe that hypomelanosis of Ito is an etiologically heterogeneous physical finding, and recommend karyotyping of multiple tissues of all patients with abnormal cutaneous pigmentation associated with developmental delay or structural malformations.

Background. Turner syndrome (gonadal dysgenesis with sex chromosome abnormalities) is recognized to be a disorder in which cardiovascular malformations are common. The prevalence and natural history of these findings, the risk for aortic dissection, and the occurrence of cardiovascular disease have all been the subject of debate, as have been the American Academy of Pediatrics recommendations for cardiac screening of patients with Turner syndrome.Objective. To evaluate a large population of patients both cross-sectionally and longitudinally to determine the prevalence of cardiovascular malformations, the risk for dissection of the aorta, to determine whether there are phenotype:karyotype correlations that can allow for specific recommendations, and to devise an appropriate screening protocol.Design and Methods. Data have been collected for patients with Turner syndrome. These individuals have been seen in an ongoing clinic established for the study of the natural history of Turner syndrome. Data from physical examinations, evaluations by cardiologists, echocardiography results, medical and surgical complications, medical records, and causes of death were analyzed. A total of 244 of 462 individuals in this population with karyotype-proven Turner syndrome could be evaluated because echocardiograms had been obtained. In addition, the medical literature was reviewed for occurrences of aortic dissection in patients with Turner syndrome.Results. A total of 136 (56%) of 244 of these patients had cardiovascular abnormalities, 96 (71%) were structural, 40 (29%) were functional, including hypertension (HBP), mitral valve prolapse and conduction defects. Coarctation of the aorta and bicuspid aortic valve, alone or in combination, comprised >50% of the cardiac malformations. Bicuspid valve was often not detected by examination, but only by echocardiography. Aortic dissection occurred in three of the patients. In one, it was traumatic; in a second, it occurred at the site of coarctation repair. The third patient had long-standing HBP with malignant obesity. In the literature, there have been 42 case reports of aortic dissection in Turner syndrome. In all except 5, predisposing risk factors of coarctation, bicuspid aortic valve, and/or HBP were present. Of these 5, sufficient information regarding predisposing risk factors was provided for only 2. No phenotype:karyotype correlations could be drawn with any certainty.Conclusions. When the diagnosis of Turner syndrome is made, a screening echocardiogram should be obtained. Referral to a cardiologist first may be appropriate, but physical examination does not substitute for visualization. Individuals with and without evidence of structural cardiac malformations should be monitored for HBP on a lifelong basis. In the absence of structural cardiac malformations or HBP, the risk for aortic dissection appears small, and repeated echocardiography or magnetic resonance imaging to follow aortic root diameters does not appear to be warranted based on data currently available. Protocols for following patients with structural malformations need to be individualized, and wholesale recommendations have little merit. A longitudinal study using magnetic resonance imaging or cardiac echocardiography to establish normal parameters for aortic root diameters and to follow aortic root changes is needed.

I read with great interest the article by Luther and colleagues in a recent issue of theArchives 1 reviewing their herculean analysis of the development of melanocytic nevi over time in children. However, the authors presented no information regarding patients' family histories of melanocytic nevi. Although Luther et al looked at predisposing risk factors that may be genetic in origin, eg, hair color and skin color, they did not appear to evaluate what is probably the single most important factor in regard to the development of nevi: the presence of nevi in a parent. My second concern is whether there is any correlation between the number of nevi at the first visit and the number developed over time. In other words, do children who have greater numbers of nevi in early childhood have a higher risk to develop even proportionately greater numbers over time, or is sun exposure itself

Epidermolysis bullosa simplex—Dowling-Meara (EBS-DM) is a severe form of EBS, with oral and nail involvement as well as severe skin blistering. Reports1,2of treatment with 5-hydroxytryptamine—2 antagonists reducing the severity of blisters in subjects with EBS-DM prompted us to study cyproheptadine hydrochloride therapy in 13 individuals with a diagnosis of EBS-DM confirmed by electron microscopic examination. Participants served as their own controls. There was a 2-week observational period, an initial 6-week period during which cyproheptadine was taken daily, a 4-week period with no treatment, and a second 6-week regimen of daily administration of cyproheptadine. Standard dosages of cyproheptadine were used.3The study was designed in this manner in an attempt to compensate for temporal variation in blister formation as well as variations in season, weather, and activity levels of the participants. Subjects were asked to record the number of blisters lanced each day rather than the

Advances in technology have resulted in an explosion of information about the molecular bases of human inheritance and human disease. Much of the new terminology is daunting, and it is becoming increasingly difficult to remain current. This article briefly reviews some of the changes in our understanding of the rules of inheritance and recurrence risks for genetic disorders. Further readings are suggested, and a glossary of technical terms is provided. ( Arch Dermatol. 1993;129:1409-1416) You and I grew up in simpler times when the laws of Mendel the geneticist were immutable and pure. (As Melodie Williams and F. Clarke Fraser pointed out in their article on Clouston ectodermal dysplasia [ Can Med Assoc J. 1967;96:36-38], the laws of Mendel the monk are frequently transgressed.) Peas were round or wrinkled, eyes were blue or brown, and your parents' blood groups were, hopefully, compatible with yours. Once we had mastered the concepts of autosomal

Hypohidrotic ectodermal dysplasia (HED) is a welldescribed, X-linked recessive disorder characterized by hypohidrosis, hypodontia, and hypotrichosis in males. Reports of similarly affected females have suggested autosomal recessive inheritance in some families. The evidence for two clinically identical but genetically distinct disorders is not convincing, however. In two families with X-linked recessive inheritance of HED, the condition was severe in females. A critical review of previously reported cases of presumed autosomal recessive HED suggests that an autosomal recessive form of the condition identical to the X-linked HED may not exist. All sporadic instances of females with classic HED should be considered to be X-linked recessive, and counseling for X-linked recessive inheritance as well as autosomal recessive inheritance should be given.

A variety of procedures have been recommended for post-mortem examination of stillbirths to determine the cause of the loss of the pregnancy and to provide an estimate of the risk of recurrence. We studied the relative usefulness of several such techniques, including gross and microscopical autopsy, photography, radiography, bacterial cultures, and chromosome studies. In 44 (35 per cent) of 124 cases of stillbirth or early neonatal death, structural physical abnormalities were evident at autopsy. In 35 of the 44 cases the abnormalities were due to chromosomal, single-gene, or polygenic disorders. The single most useful examination was the gross autopsy. Analysis of the various procedures suggests that when resources are limited, gross autopsy, photography, radiography, and bacterial cultures should be performed in all cases of stillbirth and early neonatal death, but that karyotyping and histopathology may be used selectively. This approach should minimize the use of expensive, low-yield procedures without compromising the ability to provide information for purposes of genetic counseling.

Prenatal diagnosis for many genodermatoses is available by amniocentesis, ultrasonography, chorionic villus sampling, and fetoscopy. As knowledge about the basic biochemical and DNA defects for the inherited disorders of the skin is gained, more disorders will be amenable to antenatal detection. Included is a discussion of currently available techniques and disorders successfully diagnosed or excluded.

Congenital leukemia is a rare disease that can become manifest soon after birth. Cutaneous involvement consists of red, brown, or purple papules and nodules, and confluent areas of purpura. The diagnosis is established by the presence of leukemic cells in biopsy specimens of bone marrow and involved skin, and by immunocytochemical characterization of these cells. We report a case of congenital monocytic leukemia with a normal karyotype, whose disease underwent temporary spontaneous regression.

The hereditary palmar-plantar keratodermas are a heterogeneous group of disorders characterized by hyperkeratosis of the palms and soles and distinguishable by other clinical characteristics, associated abnormalities, and mode of inheritance. We report a family with a new autosomal dominant condition with clinical similarities to mal de Meleda and Greither's disease. Biochemical characteristics before and during treatment with oral isotretinoin were typical of hyperproliferative epithelium with expression of the 48-kd keratin. Ultrastructural abnormalities were qualitatively reduced during treatment, but the abnormal keratohyaline aggregations were still seen. Clinical improvement with treatment was marked and directly correlated with dosage.

Rapp-Hodgkin ectodermal dysplasia is an autosomal dominant condition characterized by distinctive craniofacies, cleft lip or palate, dental hypoplasia with caries, dystrophic nails, and decreased to absent sweat glands and hair follicles. We report the third family to be described, and distinguish the condition from similar syndromes.

This paper presents results from a detailed assessment of the psycho-social adaptation of a group of adult women with Turner syndrome. Thirty subjects, 21 to 48 years of age, participated in an evaluation of social and psychiatric status. The evaluation included a semi-structured interview designed to assess current social functioning and past psychiatric and social history. Subjects completed two self-report questionnaires as well: the Tennessee Self-Concept Scale and the Carroll Rating Scale for Depression. The results reveal a significant subgroup of subjects reporting major psychiatric difficulties and endorsing a considerably impaired sense of self-esteem. These women presented as very dissatisfied with themselves and their lives. These findings are not consistent with previous reports in which women with Turner syndrome have been described as having an unusually high tolerance for stress and being emotionally inert.