Epidemiology of aplasia cutis congenita: A population-based study in Europe.

BACKGROUND: Aplasia cutis congenita (ACC) is a rare congenital anomaly characterized by localized or widespread absence of skin at birth, mainly affecting the scalp. Most information about ACC exists as individual case reports and medium-sized studies. OBJECTIVES: This study aimed to investigate the epidemiology of ACC, using data from a large European network of population-based registries for congenital anomalies (EUROCAT). METHODS: Twenty-eight EUROCAT population-based registries in 16 European countries were involved. Poisson regression models were exploited to estimate the overall and live birth prevalence, to test time trends in prevalence between four 5-year periods and to evaluate the impact of the change of coding for ACC from the unspecific ICD9-BPA code to the specific ICD10 code. Proportions of ACC cases associated with other anomalies were reported. RESULTS: Five hundred cases were identified in the period 1998-2017 (prevalence: 5.10 per 100,000 births). Prevalence across 5-year periods did not differ significantly and no significant differences were evident due to the change from ICD9 to ICD10 in ACC coding. Heterogeneity in prevalence was observed across registries. The scalp was the most common site for ACC (96.4%) and associated congenital anomalies were present in 33.8% of cases. Patau and Adams-Oliver syndromes were the most frequent among the associated chromosomal anomalies (88.3%) and the associated genetic syndromes (57.7%), respectively. 16% of cases were associated with limb anomalies and 15.4% with congenital heart defects. A family history of ACC was found in 2% of cases. CONCLUSION: To our knowledge, this is the only population-based study on ACC. The EUROCAT methodologies provide reliable prevalence estimates and proportions of associated anomalies.

Interfamilial clinical variability in four Polish families with cranioectodermal dysplasia and identical compound heterozygous variants in WDR35.

Cranioectodermal dysplasia (CED) is a rare autosomal recessive disorder primarily characterized by craniofacial, skeletal, and ectodermal abnormalities. CED is a chondrodysplasia, which is part of a spectrum of clinically and genetically heterogeneous diseases that result from disruptions in cilia. Pathogenic variants in genes encoding components of the ciliary transport machinery are known to cause CED. Intra- and interfamilial clinical variability has been reported in a few CED studies and the findings of this study align with these observations. Here, we report on five CED patients from four Polish families with identical compound heterozygous variants [c.1922T>G p.(Leu641Ter) and c.2522A>T; p.(Asp841Val)] in WDR35. The frequent occurrence of both identified changes in Polish CED families suggests that these variants may be founder mutations. Clinical evaluation of the CED patients revealed interfamilial clinical variability among the patients. This includes differences in skeletal and ectodermal features as well as variability in development, progression, and severity of renal and liver insufficiency. This is the first report showing significant interfamilial clinical variability in a series of CED patients from unrelated families with identical compound heterozygous variants in WDR35. Our findings strongly indicate that other genetic and non-genetic factors may modulate the progression and expression of the patients' phenotypes.

RASopathies: A significant cause of polyhydramnios?

OBJECTIVE: The aim of the study is to determine the prevalence of RASopathies in a polyhydramnios cohort selected by postnatal medical genetics evaluation. METHODS: In this retrospective study, we reviewed 622 pregnancies with polyhydramnios seen at Lucile Packard Children's Hospital between 2008 and 2017. The findings from 131 cases evaluated by Medical Genetics were included in our final analysis. Genetic testing information was extracted to determine the rate of chromosomal or single gene conditions focusing on the RASopathies. Additional variables collected were: maternal characteristics, ultrasound findings, and the severity and timing of diagnosis of polyhydramnios. RESULTS: Postnatal genetic testing or clinical examination identified a genetic disorder in 63 (48.1%) cases, more than half (n = 33) of which had a single gene condition. Postnatal testing revealed an underlying RASopathy in 15 (11.5%) cases. An underlying RASopathy was significantly associated with the severity and timing of polyhydramnios (p < 0.05). CONCLUSION: Focusing on a selected cohort postnatally evaluated by Medical Genetics, our study identified a chromosomal or genetic disorder in almost half of pregnancies complicated by polyhydramnios. Specifically, an underlying RASopathy was found in 11.5% of cases with 13/15 of these cases having additional ultrasound findings.

Cleft Lip and Palate in Ectodermal Dysplasia.

OBJECTIVE: Ectodermal dysplasia (ED) comprises multiple syndromes that affect skin, hair, nails, and teeth, and sometimes are associated with orofacial clefting. The purpose of this study is to (1) identify the prevalence and characteristics of cleft lip and/or palate (CL/P) in patients with ED and (2) describe the management and outcomes. DESIGN: Retrospective review from 1990 to 2019. PATIENTS: All patients with ED treated at Boston Children's Hospital. MAIN OUTCOMES MEASURES: Prevalence of CL/P was calculated and clinical details recorded: phenotypic anomalies, cleft type, operative treatment, and results of repair. RESULTS: Of 170 patients with a purported diagnosis of ED, 24 (14%) had CL/P. Anatomic categories were bilateral CL/P (67%), unilateral CL/P (8%), and cleft palate only (25%). The most common ED syndrome (37%) was ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC). Pathogenic variants in TP63 were the most frequent finding in the 11 patients who had genetic testing. Aberrations from a typical clinical course included failure of presurgical dentofacial orthopedics, dehiscence of nasolabial adhesion, and total palatal absence requiring free-flap construction. Two patients had prolonged postoperative admission for respiratory infection. High fistula (8%) and velopharyngeal insufficiency (33%) rates reflected the predominance of bilateral complete forms. CONCLUSIONS: As in other types of syndromic CL/P, cleft phenotypic expression in ED is more severe than the general cleft population. Further studies are needed to correlate genotype and phenotype for the distinct syndromes included in the ED spectrum.

Aplasia cutis congenita in Korea: Single center experience and literature review.

BACKGROUND: Aplasia cutis congenita (ACC) is a rare congenital malformation characterized by a localized absence of skin. which most commonly affects the scalp. We performed the present study to elucidate the basic clinical data regarding ACC in Korea, including demographics, clinical features, radiological and therapeutic results. METHODS: Fifty-nine patients (70 lesions) with ACC (35 from our department and 24 from a Koreamed database search) were enrolled. We assessed demographics, family and obstetrical histories, clinical features (multiplicity, subtype, size, shape, hair collar sign, location, and Frieden's classification), and radiologic and therapeutic results. RESULTS: The mean age of patients was 2.62 years, with a male-to-female ratio of 1.03. A minority of patients had a family history (three patients), birth trauma (one patient), maternal drug use (two patients), or human immunodeficiency virus infection (one patient) during pregnancy, and fetus papyraceus of placental infarcts (two patients). Six patients (6/59, 10.17%) had multiple lesions. Scarring was the most common manifestation (39/70, 55.71%). The scalp was the most commonly affected site (50 cases, 71.43%). Thirty-nine patients (66.10%) met Frieden's type I classification (scalp ACC without multiple anomalies). Radiological investigations were performed in 30 patients (30/59, 50.85%) with abnormal findings in eight patients. Twenty-five patients (42.37%) were managed conservatively, and 17 patients (28.81%) were treated with local wound care. CONCLUSIONS: This is the first and largest study assessing the basic clinical data of ACC in Korea. The results of the present study could be useful for pediatricians and dermatologists who routinely manage ACC.

Pain in individuals with RASopathies: Prevalence and clinical characterization in a sample of 80 affected patients.

Pain in individuals with RASopathies is a neglected topic in literature. In this article, we assessed prevalence and profile of pain in a sample of 80 individuals affected by RASopathies. The study sample included individuals with Noonan syndrome (N = 42), Costello syndrome (N = 17), and cardio-facio-cutaneous syndrome (N = 21). A set of standardized questionnaires and scales were administered (VAS/numeric scale, r-FLACC, Wang-Baker scale, NPSI, BPI, NCCPC-R) to detect and characterize acute and chronic pain and to study the influence of pain on quality of life (PEDs-QL, SF-36) and sleeping patterns (SDSC); revision of past medical history and multisystemic evaluation was provided. Available clinical data were correlated to the presence of pain. High prevalence of acute (44%) and chronic (61%) pain was documented in the examined sample. Due to age and intellectual disability, acute pain was localized in 18/35 individuals and chronic pain in 33/49. Muscle-skeletal and abdominal pain was more frequently reported. The intensity of acute and chronic pain interfered with daily activities in 1/3 of the sample. Pain negatively impacted on QoL and sleeping patterns. This work documents that pain is highly prevalent in RASopathies. Future studies including subjective and objective measures of pain are required to discriminate a somatosensory abnormality from an abnormal elaboration of painful stimuli at a central level.

Acro-Dermato-Ungual-Lacrimal-Tooth Syndrome: An Uncommon Member of the Ectodermal Dysplasias.

Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome is a rare form of autosomal dominant ectodermal dysplasia due to mutations in the TP63 gene, a locus that has also been implicated in other syndromic forms of ectodermal dysplasia. It shares many phenotypic characteristics with other TP63 gene mutation syndromes, often making an accurate diagnosis difficult. Long-term management and follow-up of the various sequelae of ectodermal dysplasia require an accurate diagnosis. We report a familial case of ADULT syndrome in a daughter, mother, and son and provide a brief review of the clinical characteristics of this syndrome.

Hair loss in infancy.

Hair diseases represent a significant portion of cases seen by pediatric dermatologists although hair has always been a secondary aspect in pediatricians and dermatologists training, on the erroneous basis that there is not much information extractable from it. Dermatologists are in the enviable situation of being able to study many disorders with simple diagnostic techniques. The hair is easily accessible to examination but, paradoxically, this approach is often disregarded by non-dermatologist. This paper has been written on the purpose of trying to serve in the diagnostic process of daily practice, and trying to help, for example, to distinguish between certain acquired and some genetically determined hair diseases. We will focus on all the data that can be obtained from our patients' hair and try to help on using the messages given by hair for each patient. Quite often it is extremely hard to distinguish between abnormality and normality in neonatal hair aspects. We will specially focus in the most common physiological changes that may mislead to an incorrect diagnosis. Specific treatment for those hair diseases that do have one, and basic general approach to improve the cosmetic appearance of hair, will be also be discussed for those hair disturbances that do not have a specific treatment.

Ectodermal dysplasia and cholesteatoma: A cross-sectional analysis of otologic issues.

OBJECTIVES: Previous studies have also associated cleft palate with increased cholesteatoma risk. Despite this close relation, the incidence of cholesteatoma and associated otologic issues in patients with ectodermal dysplasia types highly associated with cleft palate (EDT-ACPs) has not been formally analyzed. This study provides insight to guide clinicians caring for patients with ED types associated with cleft palate. METHODS: Individuals with TP63 disorders and Goltz syndrome/Focal Dermal Hypoplasia in the National Foundation for Ectodermal Dysplasia database were contacted for participation in an online REDCap survey from Sept-Dec '22. Descriptive statistics were generated using SAS JMP Pro 17 statistical software. RESULTS: 65 individuals participated in the survey (response rate approx. 18 %). The median [IQR] age was 22 [14, 43], 41 (63 %) were female, and Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate Syndrome (EEC) was most common (n = 26, 40 %). We found that, among our respondents with a history of cleft palate, the incidence of cholesteatoma was 39 %. Among respondents without a history of cleft palate, the incidence of cholesteatoma was 13 % CONCLUSIONS: Otologic issues, such as cholesteatoma, can have permanent implications including hearing loss that can be minimized by early identification and treatment. The estimated incidence of cholesteatoma among our participants is far above the estimated incidence of cholesteatoma in the general population with and without a history of cleft palate, suggesting an independent contribution of EDT-ACPs to the risk of cholesteatoma.

Prevalence and Patient Characteristics of Ectodermal Dysplasias in Denmark.

Importance: Ectodermal dysplasias constitute a group of rare genetic disorders of the skin and skin appendages with hypodontia, hypotrichosis, and hypohidrosis as cardinal features. There is a lack of population-based research into the epidemiology of ectodermal dysplasias. Objective: To establish a validated population-based cohort of patients with ectodermal dysplasia in Denmark and to assess the disease prevalence and patient characteristics. Design, Setting, and Participants: This nationwide cohort study used individual-level registry data recorded across the Danish universal health care system to identify patients with ectodermal dysplasias from January 1, 1995, to August 25, 2021. A 3-level search of the Danish National Patient Registry and the Danish National Child Odontology Registry was conducted to identify patients with diagnosis codes indicative of ectodermal dysplasias; patients registered in the Danish RAREDIS Database, the Danish Database of Genodermatoses, and local databases were also added. The search results underwent diagnosis validation and review of clinical data using medical records. Of 844 patient records suggestive of ectodermal dysplasias, 791 patients (93.7%) had medical records available for review. Positive predictive values of the diagnosis coding were computed, birth prevalence was estimated, and patient characteristics were identified. Data analysis was performed from May 4 to December 22, 2023. Results: The identified and validated study cohort included 396 patients (median [IQR] age at diagnosis, 13 [4-30] years, 246 females [62.1%]), of whom 319 had confirmed ectodermal dysplasias and 77 were likely cases. The combined positive predictive value (PPV) for ectodermal dysplasia-specific diagnosis codes was 67.0% (95% CI, 62.7%-71.0%). From 1995 to 2011, the estimated minimum birth prevalence per 100 000 live births was 14.5 (95% CI, 12.2-16.7) for all ectodermal dysplasias and 2.8 (95% CI, 1.8-3.8) for X-linked hypohidrotic ectodermal dysplasias. A molecular genetic diagnosis was available for 241 patients (61%), including EDA (n = 100), IKBKG (n = 55), WNT10A (n = 21), TRPS1 (n = 18), EDAR (n = 10), P63 (n = 9), GJB6 (n = 9), PORCN (n = 7), and other rare genetic variants. Conclusions and Relevance: The findings of this nationwide cohort study indicate that the prevalence of ectodermal dysplasias was lower than previously reported. Furthermore, PPVs of the search algorithms emphasized the importance of diagnosis validation. The establishment of a large nationwide cohort of patients with ectodermal dysplasias, including detailed clinical and molecular data, is a unique resource for future research in ectodermal dysplasias.

Clinical, genetic, epidemiologic, evolutionary, and functional delineation of TSPEAR-related autosomal recessive ectodermal dysplasia 14.

TSPEAR variants cause autosomal recessive ectodermal dysplasia (ARED) 14. The function of TSPEAR is unknown. The clinical features, the mutation spectrum, and the underlying mechanisms of ARED14 are poorly understood. Combining data from new and previously published individuals established that ARED14 is primarily characterized by dental anomalies such as conical tooth cusps and hypodontia, like those seen in individuals with WNT10A-related odontoonychodermal dysplasia. AlphaFold-predicted structure-based analysis showed that most of the pathogenic TSPEAR missense variants likely destabilize the ß-propeller of the protein. Analysis of 100000 Genomes Project (100KGP) data revealed multiple founder TSPEAR variants across different populations. Mutational and recombination clock analyses demonstrated that non-Finnish European founder variants likely originated around the end of the last ice age, a period of major climatic transition. Analysis of gnomAD data showed that the non-Finnish European population TSPEAR gene-carrier rate is ∼1/140, making it one of the commonest AREDs. Phylogenetic and AlphaFold structural analyses showed that TSPEAR is an ortholog of drosophila Closca, an extracellular matrix-dependent signaling regulator. We, therefore, hypothesized that TSPEAR could have a role in enamel knot, a structure that coordinates patterning of developing tooth cusps. Analysis of mouse single-cell RNA sequencing (scRNA-seq) data revealed highly restricted expression of Tspear in clusters representing enamel knots. A tspeara -/-;tspearb -/- double-knockout zebrafish model recapitulated the clinical features of ARED14 and fin regeneration abnormalities of wnt10a knockout fish, thus suggesting interaction between tspear and wnt10a. In summary, we provide insights into the role of TSPEAR in ectodermal development and the evolutionary history, epidemiology, mechanisms, and consequences of its loss of function variants.

Prevalence and clinical features of Costello syndrome and cardio-facio-cutaneous syndrome in Japan: findings from a nationwide epidemiological survey.

Costello syndrome and cardio-facio-cutaneous (CFC) syndrome are congenital anomaly syndromes characterized by a distinctive facial appearance, heart defects, and intellectual disability. Germline mutations in HRAS cause Costello syndrome, and mutations in KRAS, BRAF, and MAP2K1/2 (MEK1/2) cause CFC syndrome. Since the discovery of the causative genes, approximately 150 new patients with each syndrome have been reported. However, the clinico-epidemiological features of these disorders remain to be identified. In order to assess the prevalence, natural history, prognosis, and tumor incidence associated with these diseases, we conducted a nationwide prevalence study of patients with Costello and CFC syndromes in Japan. Based on the result of our survey, we estimated a total number of patients with either Costello syndrome or CFC syndrome in Japan of 99 (95% confidence interval, 77-120) and 157 (95% confidence interval, 86-229), respectively. The prevalences of Costello and CFC syndromes are estimated to be 1 in 1,290,000 and 1 in 810,000 individuals, respectively. An evaluation of 15 adult patients 18-32 years of age revealed that 12 had moderate to severe intellectual disability and most live at home without constant medical care. These results suggested that the number of adult patients is likely underestimated and our results represent a minimum prevalence. This is the first epidemiological study of Costello syndrome and CFC syndrome. Identifying patients older than 32 years of age and following up on the patients reported here is important to estimate the precise prevalence and the natural history of these disorders.

Prevalence of atopic disorders and immunodeficiency in patients with ectodermal dysplasia syndromes.

BACKGROUND: Ectodermal dysplasia (ED) syndromes are a diverse group of disorders that affect multiple ectodermally derived tissues. Small studies and case reports suggest an increase in atopy and primary immunodeficiencies (PIDs) among patients with ED syndromes. OBJECTIVE: To determine the prevalence of clinical symptoms suggestive of atopy or immunodeficiency among a large cohort of children with ED syndromes. METHODS: A 9-page questionnaire was mailed to families who were members of the National Foundation for Ectodermal Dysplasias. The surveys were completed by parents of children younger than 18 years with a diagnosis of an ED syndrome or carrier state. Portions of the questionnaire were adapted from previously validated questionnaires developed by the International Study of Asthma and Allergies in Childhood (ISAAC). RESULTS: We received 347 completed questionnaires (41%). When compared with the 13- to 14-year-old children surveyed by ISAAC, we found both all-aged and age-matched children with ED syndromes, respectively, had significantly higher rates of asthma (32.2% and 37.2% vs 16.4%), rhinitis symptoms (76.1% and 78.3% vs 38.9%), and eczema (58.9% and 48.9% vs 8.2%). The prevalence of physician-diagnosed food allergies (20.7%) and PIDs (6.1%) in these ED patients also exceeded known rates in the general pediatric population. CONCLUSION: This large-scale, retrospective study demonstrates a greater reported prevalence of symptoms suggestive of atopic disorders and PIDs among children with ED syndromes than the general pediatric population. A combination of genetic and environmental factors in ED syndromes may contribute to breaches of skin and mucosal barriers, permitting enhanced transmission and sensitization to irritants, allergens, and pathogens.

Recognizable neonatal clinical features of aplasia cutis congenita.

BACKGROUND: Aplasia cutis congenita (ACC), classified in nine groups, is likely to be underreported, since milder isolated lesions in wellbeing newborns could often be undetected, and solitary lesions in the context of polymalformative syndromes could not always be reported. Regardless of form and cause, therapeutic options have in common the aim to restore the deficient mechanical and immunological cutaneous protection and to limit the risk of fluid leakage or rupture of the exposed organs. We aimed to review our institutional prevalence, comorbidities, treatment and outcome of newborns with ACC. METHODS: We conducted a retrospective study including all newborns affected by ACC and admitted at the University Mother-Child Department from October 2010 to October 2019. Anthropometric and clinical characteristics of ACC1 versus a non-isolated ACC group were analyzed. RESULTS: We encountered 37 newborns, 16 with ACC1 versus 21 with non-isolated ACC. The incidence rate of 0.1% in ACC1 was higher than expected, while 19% of cases showed intrafamilial autosomal dominant transmission. Higher birth weight centile, though lower than reference population, being adequate for gestational age, normal Apgar score and euglycemia characterizing ACC1 resulted associated to a rapid tissue regeneration. Non-isolated ACC, in relation to concomitant congenital anomalies and higher prematurity rate, showed more surgical and medical complications along with the risk of neonatal death. Specifically, newborns with ACC4 were characterized by the frequent necessity of abdominal wall defect repair, responsible for the occurrence of an abdominal compartment syndrome. CONCLUSION: Prompt carefully assessment of the newborn with ACC in order to exclude concomitant other congenital malformations, provides clues to the underlying pathophysiology, and to the short-term prognosis. Family should be oriented toward identification of other family members affected by similar pathology, while obstetric history should exclude initial multiple pregnancy with death of a co-twin, placental anomalies and drug assumption. Molecular-genetic diagnosis and genetic counseling are integrative in individualized disease approach.

Self-Assessment of Oral Health-Related Quality of Life in People with Ectodermal Dysplasia in Germany.

Background: Ectodermal dysplasia describes a heterogeneous group of hereditary, congenital malformations involving developmental dystrophies of ectodermal structures. The aim of this study was to analyse the oral health-related quality of life (OHRQoL) in people with ectodermal dysplasia and to evaluate the influence of different variables. Methods: The study was designed as an anonymous epidemiological survey study among people with ectodermal dysplasia to evaluate oral symptoms, satisfaction with the health system and their respective OHRQoL using the validated German version of the OHIP-14 (Oral Health Impact Profile) questionnaire. Results: When asked about oral symptoms, 110 of the participants provided responses, of which 109 (99.09%) described oral symptoms. The average age of the female participants at the time of diagnosis was 17.02 years (range: 0 to 48 years), the average age of men was 5.19 years (range: 0 to 43 years). The average OHIP-14 overall score for female participants was 12.23 points (SD: 12.39), for male participants an average OHIP score of 11.79 points was recorded (SD: 11.08 points). Difficulty in finding a dentist (p = 0.001), and the dissatisfaction with the health system (p = 0.007) showed a negative impact on the OHRQoL. Conclusion: People with ectodermal dysplasia rate their OHRQoL worse than is usually prevalent in the normal German population (4.09 points); women are diagnosed with "ectodermal dysplasia" later than men. Participants who reported difficulties in finding a dentist for treatment exhibited higher OHIP values. Likewise, dissatisfaction with the health system demonstrated a negative impact on the oral health-related quality of life.

Head and neck manifestations and quality of life of patients with ectodermal dysplasia.

OBJECTIVES: Ectodermal dysplasias (EDs) are a group of genetic disorders characterized by deficient ectodermal and mesodermal development. Studies examining resultant otolaryngologic issues are few. The objectives of this study were to delineate the head and neck manifestations and quality of life in EDs. STUDY DESIGN AND SETTING: For 75 individuals, comprehensive histories were taken and otolaryngologic examinations were performed, and subjects rated their otolaryngologic symptom severity. A validated quality of life instrument (SF-8) was administered. RESULTS: The majority of subjects had a diagnosis of hypohidrotic ED (72%). Otolaryngologic conditions included otitis media (28%), cerumen impaction (48%), nasal obstruction/crusting (51%), heat intolerance (76%), and eczema (39%). Physical findings included peg teeth/hypodontia (76%), alopecia (41%), nasal crusting (41%), and saddle nose deformity (44%). Quality of life scores were generally high. Overall, health was rated "good to excellent" by 87 percent. CONCLUSION: Patients with ED frequently experience significant otolaryngologic symptoms, although most patients report a good quality of life. SIGNIFICANCE: A greater understanding of the otolaryngologic issues in ED should help facilitate diagnosis and improve management.

Lobster-claw hand: a manifestation of EEC syndrome.

The combination of ectrodactyly, ectodermal dysplasia, and cleft lip with or without cleft palate (EEC syndrome) is a rare type of congenital anomaly. It usually occurs as an autosomal-dominant trait or less commonly in a sporadic form. In this complex, multiple congenital anomaly syndrome, any of the three cardinal manifestations may present with variable expressions.

Genetic hair and nail disorders.

Hair and nails are skin appendages that share with other ectodermal tissues a common developmental pathway. Inherited disorders affecting these two structures therefore very often involve other epithelial components and present with multiple anomalies, generating both physical and psychological distress among patients and their families. The present review briefly describes major recent advances in our understanding of hair and nail genodermatoses.

Urinary tract involvement in EEC syndrome: a clinical study in 25 Brazilian patients.

We have evaluated 25 patients (14 isolated and 11 familial cases) with the EEC syndrome for genitourinary (GU) tract anomalies through intravenous pyelogram (IVP), voiding urethrocystography, and sonographic examination. Fifty-two percent of the patients (7 isolated and 6 familial cases) had involvement of the urinary tract, with no significant difference between isolated and familial cases. The present data seem to reflect the best estimate of the prevalence of genitourinary anomalies in patients with the EEC syndrome.