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The etiology of hypospadias and cryptorchidism, which are the two most common genital anomalies in males, has not been elucidated. Although prenatal exposure to endocrine-disrupting chemicals (EDCs) may increase the risks of hypospadias and cryptorchidism, the associations have not been confirmed. Therefore, we performed a meta-analysis to establish the relationships between prenatal exposure to EDCs and male genital anomalies. A systematic search of PubMed, EMbase, and Cochrane Library CENTRAL for relevant published studies providing quantitative data on the associations between prenatal EDCs exposure and hypospadias/cryptorchidism in humans was conducted. In total, sixteen case-controlled studies were included. Prenatal exposure to overall EDCs was associated with an increased risk of hypospadias in males (OR, 1.34, 95 % CI 1.12 to 1.60). Although there was no statistically significant association between overall EDCs exposure and cryptorchidism (OR, 1.11, 95 % CI 0.99 to 1.24), exposure to phenol substances was associated with an increased risk of cryptorchidism (OR, 1.81, 95 % CI, 1.12 to 2.93). Using the GRADE tool, we found the overall evidence to be of moderate certainty. In conclusion, the current evidence suggests prenatal EDCs exposure may increase the risk of hypospadias in males.

Background: There are a growing number of reports on the association between air pollution and the risk of congenital anomalies. However, the results are inconsistent and most studies have only focused on the association of air pollution with congenital heart defects and orofacial clefts.Objectives: Using an exploratory study design, we aimed to identify congenital anomalies that may be sensitive to maternal exposure to specific air pollutants during the periconceptional period.Methods: We conducted a case-control study of 7426 subjects born in the 15 years between 1999 and 2014 and registered in the European Registration of Congenital Anomalies and Twins Northern Netherlands (EUROCAT NNL). Concentrations of various air pollutants (PM10, PM2.5, PM10-2.5, NO2, NOx, absorbance) were obtained using land use regression models from the European Study of Cohorts for Air Pollution Effects (ESCAPE). We linked these data to every subject in the EUROCAT NNL registry via their full postal code. Cases were classified as children or fetuses born in the 15-year period with a major congenital anomaly that was not associated with a known monogenic or chromosomal anomaly. Cases were divided into anomaly subgroups and compared with two different control groups: control group 1 comprised children or fetuses with a known monogenic or chromosomal anomaly, while control group 2 comprised all other non-monogenic and non-chromosomal registrations.Results: Using control group 1 (n = 1618) for analysis, we did not find any significant associations, but when we used control group 2 (ranges between n = 4299 and n = 5771) there were consistent positive associations between several air pollutants (NO2, PM2.5, PM10-2.5, absorbance) and the genital anomalies subgroup.Conclusion: We examined various congenital anomalies and their possible associations with a number of air pollutants in order to generate hypotheses for future research. We found that air pollution exposure was positively associated with genital anomalies, mainly driven by hypospadias. These results broaden the evidence of associations between air pollution exposure during gestation and congenital anomalies in the child. They warrant further research, which should also focus on possible underlying mechanisms.

Urethral duplication in a female is a rare congenital anomaly. The clinical presentation varies from being asymptomatic to double stream, incontinence, genital anomalies, and urinary infections. The management is also tailor made to the clinical presentation. We describe a case of urethral duplication in an adult female who presented to us with clitoral voiding.

Congenital unilateral renal agenesis is a relatively frequent condition at birth diagnosed mostly incidentally. Despite the excellent prognosis, unilateral renal agenesis is associated with an increased risk of other structural abnormalities, including genital malformations. The authors present two cases of asymptomatic adolescents with known congenital unilateral renal agenesis and associated genital malformations solely diagnosed during puberty—a man with Zinner syndrome and a female with Mayer-Rokitansky-Küster-Hauser syndrome.

Adolescence is a distinctive stage in human development during which many simple and complex medical conditions can present for the first time. Paediatric and adolescent gynaecological conditions need careful multidisciplinary clinical management with a sensitive approach understanding the patients' psychological and physiological circumstances. The objective of this study is to review the tertiary paediatric and adolescent gynaecology service in Leeds, United Kingdom and to present an overview of the various conditions that present to such a clinic. A total of 985 patients were seen over a 16-year period and the increasing number of patients seen over this time establishes the need for such a service to exist. Complex developmental anomalies of the genital tract and disorders of sexual differentiation formed a major portion of the referrals. Presence of a significant number of referrals for simple gynaecological conditions including menstrual irregularities, gynaecological pain, vulvovaginitis, polycystic ovary syndrome and concerns about labial appearance indicates the reluctance of general gynaecologists and general practitioners to manage such conditions in young patients. This emphasizes the need for continued education of primary health care professionals and establishment of clear guidelines and care pathways for the management of this special patient group.

Pontocerebellar hypoplasia (PCH) can occur as an isolated entity or part of a syndrome. PCH has been reported with facial dysmorphism, ocular anomalies, and genital anomalies, but the co-occurrence of all four has not been previously described. We report on four patients, born to two consanguineous families that are not related to one another, with distinctive facial features (short forehead, laterally extended, medially flared eyebrows), corneal dystrophy, underdevelopment of labioscrotal folds, and nonprogressive PCH. In addition, the patients show hair extruding from the lactiferous ducts, which to our knowledge has not been described before. The parental consanguinity, affected siblings of both genders, and absent manifestations in parents, indicate an autosomal recessive pattern of inheritance as most likely. (C) 2016 Wiley Periodicals, Inc. Türkiye Bilimsel Ve Teknolojik Araştırma Kurumu ( Tübitak )

Carriers of isodicentric Y (idicY) mosaicism exhibit a wide range of clinical features, including short stature, gonadal abnormalities, and external genital anomalies. However, the phenotypic spectrum for individuals carrying an idicY and a 46, XX cell line is less clearly defined. A more complete description of the phenotype related to idicY is thus essential to guide management related to pubertal development, fertility, and gonadoblastoma risk in mosaic carriers. Findings from the evaluation of twin females with an abnormal karyotype, 48, XX, +idic(Yq) x2/47, XX, +idic(Yq)/46, XX, are presented to highlight the importance of interdisciplinary care in the management of multifaceted disorders of sex development.

Studies estimate that the incidence of genital anomalies could be as high as 1 in 300 births. While it is rare for an infant to present with truly ambiguous genitalia, it is plausible that the pediatric nurse will encounter a patient with disorders of sexual development in his or her career. Cases of disorders of sexual development are challenging due to complexities of diagnosis, gender assignment, uncertain outcomes, treatment options, and psychosocial stressors. This article discusses the evaluation and management of children with disorders of sexual development and the nurse's role as child advocate and family educator.

Context:\ud The focus of care in disorders of sex development (DSD) is often directed to issues related to sex and gender development. In addition, the molecular etiology remains unclear in the majority of cases.\ud Objective:\ud To report the range of associated conditions identified in the international DSD (I-DSD) Registry.\ud Design, Setting, and Patients:\ud Anonymized data were extracted from the I-DSD Registry for diagnosis, karyotype, sex of rearing, genetic investigations, and associated anomalies. If necessary, clarification was sought from the reporting clinician.\ud Results:\ud Of 649 accessible cases, associated conditions occurred in 168 (26%); 103 (61%) cases had one condition, 31 (18%) had two conditions, 20 (12%) had three conditions, and 14 (8%) had four or more conditions. Karyotypes with most frequently reported associations included 45,X with 6 of 8 affected cases (75%), 45,X/46,XY with 19 of 42 cases (45%), 46,XY with 112 of 460 cases (24%), and 46,XX with 27 of 121 cases (22%). In the 112 cases of 46,XY DSD, the commonest conditions included small for gestational age in 26 (23%), cardiac anomalies in 22 (20%), and central nervous system disorders in 22 (20%), whereas in the 27 cases of 46,XX DSD, skeletal and renal anomalies were commonest at 12 (44%) and 8 (30%), respectively. Of 170 cases of suspected androgen insensitivity syndrome, 19 (11%) had reported anomalies and 9 of these had confirmed androgen receptor mutations.\ud Conclusions:\ud Over a quarter of the cases in the I-DSD Registry have an additional condition. These associations can direct investigators toward novel genetic etiology and also highlight the need for more holistic care of the affected person.

Disorders of sex development (DSD) is a group of sexual differentiation disorders resulting in genital anomalies with defects in gonadal hormone synthesis and/or incomplete genital development. These conditions result in problems concerning the sex assignment of the child. This study aims to describe the clinical features, diagnosis and management of children with DSD in southern Thailand.The medical records of 117 pediatric patients diagnosed with DSD during the period of 1991-2011 were retrospectively reviewed.Disorders of sex development were categorized into 3 groups: sex chromosome abnormalities (53.0%), 46,XX DSD (29.9%) and 46,XY DSD (17.1%). The two most common etiologies of DSD were Turner syndrome (36.8%) and congenital adrenal hyperplasia (29.9%). Ambiguous genitalia/intersex was the main problem in 46,XX DSD (94%) and 46,XY DSD (100%). Sex reassignment was done in 5 children (4.3%) at age of 3-5 years: from male to female in 4 children (1 patient with congenital adrenal hyperplasia, 1 patient with 45,X/46,XY DSD, and 2 patients with 46,XX ovotesticular DSD) and from female to male in 1 patient with 46,XX ovotesticular DSD. Of the total 20 children with 46,XY DSD, 16 (80%) were raised as females.Management of DSD children has many aspects of concern. Sex assignment/reassignment depends on the phenotype (phallus size) of the external genitalia rather than the sex chromosome.

Introduction. Urogenital congenital anomalies are among the most common congenital anomalies and very frequent pathology in paediatric urology. Health care systems strive to shorten the duration and reduce the costs of hospitalization, while maintaining treatment effectiveness. Objective. To evaluate the duration of hospital stay of surgically treated patients with congenital urogenital anomalies and estimate the possibility of using fast track surgery principles in paediatric urology in the local settings of a developing country. Methods. Retrospective non-randomized study included 552 patients who had been surgically treated at the Urology Department of the University Children?s Hospital, during 2010. In line with their congenital anomalies, all patients were classified in one of four groups: I - upper urinary tract anomalies (252 patients); II - genital anomalies (164 patients); III - testicular anomalies (76 patients) and IV - associated anomalies (60 patients). We analyzed the total duration of stay as well as preand post-operative stay in the hospital. Results. The average duration of hospitalization was 4.7?4.0 days. Patients with testicular anomalies stayed for the shortest period (2.3?1.9 days) (p

The present stud- was conducted to evaluate the usefulness of dih-drotestosterone (DHT) binding assa- of skin fibroblasts for the differential diagnosis in infants of testicular feminization s-ndrome (TFS) from other disorders with genital anomalies. DHT binding was measured in the fibroblasts derived from the patients with intersex or genital anomalies such as TFS, incomplete TFS, pure gonadal agenesis, retentio testis, Klinefelter's s-ndrome, testicular d-sgenesis, adrenogenital s-ndrome, and Turner's s-ndrome. All patients except the TFS patients exhibited normal binding capacit- in fibroblasts from either genital or nongenital skins. The patients with TFS were 3 and 6 -ear-old siblings whose diagnosis had not been made completel- b- g-necological examination and routine laborator- tests, but the binding assa- contributed to making the exact diagnosis of these patients. DHT binding of skin fibroblasts from normal males and females was 11.5±8.6 (S. D.) fmoles/mg cell protein in nongenital skin, whereas the DHT binding assa- of these patients showed that the maximal number of binding sites was under 0.5 fmoles/mg cell protein. These results suggest that DHT binding assa- of skin fibroblasts is useful also for the prospective differential diagnosis of TFS in infant and prepubertal patients and that treatment for TFS might be planned from infanc-.

Objectives Many concerns have been raised regarding the treatment and long-term outcome of infants born with complex genital anomalies. Debate among clinicians, psychologists, ethicists, and patient advocate groups regarding the optimal management of these individuals is ongoing. Although determining the most appropriate gender is a difficult task, this review will help clarify some of the issues at hand. Methods A literature review which addresses the challenges of advising families about gender identity in infants and children with disorders of sex development. Results The evidence for endocrine effects on neurobiological development with regard to sexual behavior is compelling, although the existing outcome studies are largely anecdotal and somewhat contradictory. Conclusions Gender assignment in infants born with a disorder of sex development remains only one of the many difficult decisions faced by both the treatment team and the family. Improved long-term follow-up of these patients will provide much needed feedback on previous and contemporary management.

A sibship is reported of three brothers who all manifested short stature and identical facial, digital, and genital anomalies consistent with Aarskog's syndrome. In addition, all manifested ophthalmoplegia and growth delay of prenatal onset, features uncommon among patients previously reported with this syndrome. The mother had some of the digital anomalies seen in her three boys, but otherwise was unaffected. The pattern of inheritance seen in our family and in those previously reported indicates that the syndrome is either X-linked recessive or autosomal dominant, with limited expression in the female.

In the last decade, significant progress in the knowledge and management of external genital anomalies has been achieved, including an improved understanding of epidemiology and pathophysiology of these anomalies, the identification of etiologic genetic defects, and significant improvements in surgical approaches that have decreased complications and improved cosmetic outcomes. We highlight the most clinically important advances of the commonly encountered external genital anomalies.

Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 ( ZEB2) gene. The syndrome is characterized by typical facial features, moderate-to-severe mental retardation, epilepsy and variable congenital malformations, including Hirschsprung disease, genital anomalies, congenital heart disease, agenesis of the corpus callosum, and eye defects. The prevalence of Mowat-Wilson syndrome is currently unknown, but it seems that Mowat-Wilson syndrome is underdiagnosed, particularly in patients without Hirschsprung disease. We report here the first Egyptian case of Mowat-Wilson syndrome who was conceived by intracytoplasmic sperm injection. The patient manifested bilateral sensorineural hearing loss—a new feature not previously reported in cases of Mowat-Wilson syndrome. This report describes the first Egyptian patient of Mowat-Wilson syndrome who was conceived after intracytoplasmic sperm injection, and provides a new evidence for the inclusion of deafness among the congenital defects of the syndrome.

Genetic evidence for a novel gene(s) involved in urogenital development on 10q26. Background Although the frequent association between distal 10q monosomy and urogenital anomalies suggests the presence of a gene(s) for urogenital development on distal 10q, molecular deletion mapping has not been performed for the putative gene(s). In this study, we examined genotype-phenotype correlations in patients with distal 10q monosomy. Methods This study consisted of six karyotypic males (cases 1 through 6) and four karyotypic females (cases 7 through 10) with 10q26 monosomy. Cases 3 through 5 and 7 through 10 had urinary anomalies such as vesicoureteral reflux and hypoplastic kidney, and cases 1 through 6, 8, and 9 exhibited genital anomalies such as micropenis, hypospadias, cryptorchidism, and hypoplastic labia majora. Fluorescence in situ hybridization (FISH) for 10q telomere, whole chromosome 10 painting, and microsatellite analysis for 35 loci on distal 10q were performed in cases 1 through 8. Results FISH and whole chromosome painting confirmed distal 10q monosomy in cases 1 through 8. Microsatellite analysis revealed that hemizygosity for the region distal to D10S186 was shared by cases with urinary anomalies and that for the region distal to D10S1248 was common to cases with genital anomalies. Furthermore, it was indicated that PAX2, GFRA1, and EMX2 on distal 10q, in which the deletions could affect urinary and/or genital development, were present in two copies in cases 1 through 8. Conclusions The results suggest that a novel gene(s) for urinary development and that for genital development reside in the approximately 20cm region distal to D10S186 and in the approximately 10cm region distal to D10S1248, respectively, although it remains to be determined whether the two types of genes are identical or different.

PubMed ID: 10771823, Severely involved female child with Multiple Pterygium Syndrome (Escobar) is described. She had the typical findings of the syndrome such as multiple pterygiums, characteristic facial appearance, genital anomalies. She also had bilateral optic atrophy. This is the first case described so far with optic atrophy in Multiple Pterygium Syndrome (Escobar).

Acro-cardio-facial syndrome (ACFS) is an infrequently reported, variable condition characterized by split-hand and split-foot malformation and congenital heart defect (CHD), along with cleft lip and palate, genital anomalies, unusual face and intellectual disability. An autosomal recessive pattern of inheritance has been suggested because of affected sibs born to unaffected parents and parental consanguinity; the cause is unknown. We describe a newborn with the clinical manifestations of ACFS in whom a deletion of the region 6q21-q22.3 was detected by array CGH. We compare the clinical features of the present patient with earlier reported patients with similar 6q deletions and patients diagnosed with ACFS. The similarities between these patient groups suggest that ACFS may be a microdeletion syndrome caused by loss of the 6q21-22.3 region. The recurrence in families may be explained by prenatal germline mosaicism. Alternatively, ACFS may be a genetically heterogeneous disorder which can also be caused by biallelic mutations of an autosomal recessive gene.

An accurate diagnosis of fetal genitourinary abnormality is essential because some genitourinary abnormalities are associated with pulmonary hypoplasia, which ultimately affects the neonatal outcome. Adrenal masses are rare; however, presence of any lesion located at the superior pole of the kidney should raise the possibility of an adrenal mass. Fetal genital anomalies are rare as well and some of the most difficult to diagnose. A combination and pattern of findings allows for specific diagnosis of renal tract abnormalities. This article reviews the imaging appearance of fetal genitourinary abnormalities with perinatal imaging correlation where available.

Multiple pterygium syndrome is a rare, inherited disorder manifested by growth retardation, facial or genital anomalies, and widespread musculoskeletal deformities. Pterygia are the predominant hallmark of the syndrome. Five children with multiple pterygium syndrome were treated from 1978 to 1987. Treatment involved both upper and lower pterygia and contractures. The results of treatment and modalities used are discussed and a protocol suggested.

Pfeiffer-type cardiocranial syndrome (MIM 218450) was first delineated in 1987; several further patients have been reported confirming this as a distinct nosological entity. The aetiology of this condition remains unknown although an autosomal recessive pattern of inheritance has been suggested following the description of sib pairs. A patient is described with features of this condition including sagittal suture synostosis, growth retardation, learning difficulties, hypertelorism, low-set ears, micrognathia, congenital heart defects and genital anomalies. Telomere studies on blood and skin samples identified a de novo unbalanced rearrangement resulting in partial monosomy for 1p36.1 to pter and partial trisomy for 17q25.1 to qter. This case provides the first insight into the possible aetiology of this condition.

A 7 year old boy with minor facial anomalies, the Rieger eye malformation, reduced vision, genital anomalies, and severe mental retardation had deletion of the segment 4q24-- >q26. His phenotypically normal father had a balanced insertion of that segment into the distal long arm of chromosome 6: 46, XY, ins (6 ; 4) (q26 ; q24q26). Microsatellite loci flanking the RIEG gene on 4q25 were deleted giving indirect evidence of deletion of this locus. This finding and the normal ocular findings in the insertion carrier father show that haplotype insufficiency can cause the Rieger eye malformation.

Aarskog-Scott syndrome (ASS) is an X-linked disorder characterized by facial, skeletal and genital anomalies, including penoscrotal transposition in males. We report on a girl from a family with ASS who exhibits a transposition of the clitoris.

Congenital anomalies of the external genitalia occur in 2–3 per 100 infants. These anomalies might bring variable degrees of morbidity to the infant and often constitute diagnostic challenges for health professionals. We present a case report of a fetus with bilateral vulvar cysts diagnosed during the third trimester ultrasound. The cysts spontaneously regressed before birth and the newborn showed no genital anomalies at birth.

Objective: To evaluate the surgical feasibility and the long-term anatomic and functional results of a new procedure that uses the endoscopic approach to treat uterovaginal agenesis, known as Rokintansky syndrome. Design: Evaluation of surgical feasibility and recording of clinical data over a 12-month follow-up. Setting: Tertiary referral center for the treatment of female genital malformations. Patient(s): Fifty-two patients with vaginal agenesis. Intervention(s): The laparoscopic version of the Vecchietti method was used to create a neovagina. Main Outcome Measure(s): Anatomic success was defined as a neovagina ≥6 cm long, allowing easy introduction of two fingers, within 6 months after corrective surgery. Functional success was considered achieved if the patient reported satisfactory sexual intercourse starting from 6 months after surgery. Result(s): The surgical procedure was performed with no major complications and with 100% anatomic success; functional success was obtained in 98.1% of the study population. Conclusion(s): In patients with Rokitansky syndrome, the laparoscopic approach for creating a neovagina by the Vecchietti method is simple, safe, and effective.

Objectives This is a report of five cases of abnormal fetal genitalia detected by routine prenatal ultrasound. Methods Retrospective review was conducted to identify all cases of abnormal fetal genitalia identified by routine obstetrical ultrasound at our institution in which postpartum follow-up was available. Results Five cases of prenatal sonographically diagnosed abnormal fetal genitalia were confirmed postnatally. The abnormalities include ambiguous genitalia, severe hypospadias with unilateral cryptorchidism, megalourethra, and concealed penis. In all cases, other anomalies were discovered during the prenatal ultrasound. Conclusions Prenatal ultrasound may detect a variety of abnormalities of the fetal genitalia.

A 12-year-old girl with a syndrome of short stature, mental retardation and multiple, distinctive skeletal anomalies such as craniosynostosis, hamate-capitate fusion, first rib gaps, Klippel-Feil anomaly and Scheuerman-like kyphosis is reported.

The multiple pterygium syndrome is a rare autosomal recessive condition characterised by arthrogryposis multiplex congenita, pterygia of the neck, fingers, and antecubital, popliteal, and intercrural areas, growth retardation, and facial, vertebral, and genital anomalies. We present two unrelated patients of 17 and 6 years of age, respectively, affected with this condition. We describe the natural history of their disorder since birth and review the spectrum of phenotypic variation of the multiple pterygium syndrome in 25 published cases.

Magnetic resonance imaging, a new radiographic modality that is not dependent on ionizing radiation or intravenous contrast agents, was used to identify undescended testes in 11 patients. Of 14 undescended testes 13 were identified and the only testis that was not seen was in a patient with surgically proved unilateral anorchism. We also used magnetic resonance imaging in 9 patients with various types of intersex. The anatomy of the corpora cavernosa, vagina, uterus and gonads was well seen in each instance.

Agenesis of the bladder is a rare anomaly involving the development of the urogenital sinus. We report on 3 patients who survived the initial perinatal period and 2 are alive for more than 4 years. Renal and genital anomalies accompany this abnormality, and recurrent urinary tract infections and incontinence are prominent. Treatment of choice is urinary diversion in the hope of stabilizing renal function and an antirefluxing procedure is deemed preferable.

Congenital malformation continues to be a major problem for infants of diabetic mothers. Over a seven-year period, 199 insulin-requiring diabetic mothers were delivered at Vanderbilt University Medical Center. Con genital anomalies were identified in 26 (13%) newborns. There was no significant difference in the incidence of fetal anomalies between the various categories of White's classification of maternal diabetes mellitus. A review of proposed etiologies of anomalies in diabetic pregnancies is presented, and suggestions are made for the manage ment of women with dia betes desiring to conceive.

Six cases with a coexistence of endometriosis and genital anomalies among 112 patients with external endometriosis and 90 patients with genital anomaly were detected. Three cases of severe endometriosis associated with uterovaginal duplication, unilateral renal agenesis and ipsilateral blind vagina and the latter in a patient with Rokitansky-Kuster-Hauser syndrome are presented. Another case with obstructive genital anomaly without endometriosis is also presented. The histogenetic mechanisms of endometriosis are discussed. The transplantation theory is not sufficient to explain all the cases and, therefore, the theory of celomic metaplasia and the theory of müllerian remains or Cullen's theory, as well as the intervention of genetic-constitutional, immunologic, hormonal and other factors must also be considered.

Data of 13,037 live-born infants from a hospital in Tehran, Iran were analysed for congenital malformations and genetic diseases. The results showed that the rates of joint dislocation, eleft lip, cleft palate and finger anomalies are similar to those of the other populations. The rates of chromosomal, thorax and abdominal, external genital anomalies and other syndromes were higher compared with other populations, whereas the rates of multiple births and limb anomalies were lower.

A case of the Smith-Lemli-Opitz syndrome is reported in an 18-month-old boy. He presented with antenatal and postnatal growth retardation, microcephaly, convergent strabismus, broad based nose with upturned nares, a narrow high-arched palate, genital anomalies, and bilateral cutaneous syndactyly of his second and third toes. He had a normal male karyotype. The parents of the child are second cousins, a fact considered to be supporting evidence for an autosomal recessive mode of inheritance in this syndrome. Dermatoglyphic analyses of the family and in other reported cases, suggest little of diagnostic value in this technique.

Analysing 90 cases of different genital anomalies in phenotypic females a new pathogenetical classification is presented. The different anomalies are classified in 5 groups of disorders in the steps of genital development: gonadal determination, differentiation and development, genital ducts differentiation and development. Symptoms in reproductive age, diagnostic approach and therapeutic possibilities with particular attention to assisted reproduction are presented.

We report a brother and sister affected by a constellation of malformations, including cleft palate, cardiac defect, genital anomalies, and ectrodactyly (CCGE). A similar association has been reported previously by Richieri-Costa and Orquizas in a male patient born to consanguineous parents. An autosomal recessive pattern of inheritance is proposed for this syndrome.

I would like to point out two additional reports of this syndrome from the literature [Elias et al., 1978; Goeminne, 1981] and present another family with the combination of mullerian duct-distal limb anomalies (Fig. 1). In addition, several members of this family have external ear anomalies