Prenatal profile of Pallister-Killian syndrome: Retrospective analysis of 114 pregnancies, literature review and approach to prenatal diagnosis.

Pallister-Killian syndrome (PKS) is a tissue limited mosaic disorder, characterized by variable degrees of neurodevelopmental delay and intellectual disability, typical craniofacial findings, skin pigmentation anomalies and multiple congenital malformations. The wide phenotypic spectrum of PKS in conjunction with the mosaic distribution of the i(12p) makes PKS an underdiagnosed disorder. Recognition of prenatal findings that should raise a suspicion of PKS is complicated by the fragmentation of data currently available in the literature and challenges in diagnosing a mosaic diagnosis on prenatal testing. Ultrasound anomalies, especially congenital diaphragmatic hernia, congenital heart defects, and rhizomelic limb shortening, have been related to PKS, but they are singularly not specific and are not present in all affected fetuses. We have combined prenatal data from 86 previously published reports and from our cohort of 114 PKS probands (retrospectively reviewed). Summarizing this data we have defined a prenatal growth profile and identified markers of perinatal outcome which collectively provide guidelines for early recognition of the distinctive prenatal profile and consideration of a diagnosis of PKS as well as for management and genetic counseling.

Hair in newborns and infants: clinical and dermoscopic evaluation of 45 cases.

BACKGROUND: The literature still lacks comprehensive assessments on the features of neonatal hair and scalp characteristics. OBJECTIVES: To evaluate the clinical and dermoscopic features of scalp hair in newborns, including measurement of hair density, length and diameter. METHODS: Forty-five newborns were recruited for the study. For each patient, data regarding sex, age at consultation, delivery method, gestational age and maternal age at delivery were collected. A clinical score of hair density was created by investigators in order to divide the neonates into two groups: group 1 included neonates with poor and slightly poor hair density and group 2 included neonates with quite good and good hair density. Each patient underwent scalp videodermatoscopy. RESULTS: Based on their clinical score, 15 newborns had good hair density, while 30 had poor hair density. Among the parameters evaluated by the investigators, only weight at birth significantly correlated with neonatal hair density. Two neonates presented a frontal-temporal pattern of hair loss. Videodermatoscopy revealed that nine neonates, all in the poor hair density group, had a particular hair shaft dermoscopic feature, characterized by the presence of widespread thin hair. CONCLUSION: On the basis of the results obtained from our study, we propose a new classification of transient neonatal hair loss. We have found two different hair types: 'neonatal type', rarely observed, that appears in the first 4 weeks of life with a frontal-temporal pattern; and 'classic type', more frequently observed, appearing at 8-12 weeks of life with a predominant occipital pattern.

Eruption delay in a 47 XXY male: a case report.

BACKGROUND: The 47,XXY syndrome, or Klinefelter syndrome, though it is a rare occurrence, it is the most common sex choromosome disorder affecting male subjects. This syndrome is underdiagnosed and seldomly before puberty. In this case, diagnosis was made before birth, through chorion villus sampling. CASE REPORT: A 16 month-old Italian male with 47 XXY syndrome showed the absence of primary teeth, with a delay of about 8-10 months, whereas during the first 15 months of life the auxological development has been normal both in weight and height (about 50th percentile). We assumed that this delay may be linked with Klinefelter syndrome, as sexual chromosomes play an important role in the dental development.

Mowat-Wilson syndrome: facial phenotype changing with age: study of 19 Italian patients and review of the literature.

Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, and characterized by typical face, moderate-to-severe mental retardation, epilepsy, Hirschsprung disease, and multiple congenital anomalies, including genital anomalies (particularly hypospadias in males), congenital heart defects, agenesis of the corpus callosum, and eye defects. Since the first delineation by Mowat et al. [Mowat et al. (1998); J Med Genet 35:617-623], approximately 179 patients with ZEB2 mutations, deletions or cytogenetic abnormalities have been reported primarily from Europe, Australia and the United States. Genetic defects include chromosome 2q21-q23 microdeletions (or different chromosome rearrangements) in few patients, and ZEB2 mutations in most. We report on clinical and genetic data from 19 Italian patients, diagnosed within the last 5 years, including six previously published, and compare them with patients already reported. The main purpose of this review is to underline a highly consistent phenotype and to highlight the phenotypic evolution occurring with age, particularly of the facial characteristics. The prevalence of MWS is likely to be underestimated. Knowledge of the phenotypic spectrum of MWS and of its changing phenotype with age can improve the detection rate of this condition.

An intermediate phenotype between Hay-Wells and Rapp-Hodgkin syndromes in a patient with a novel P63 mutation: confirmation of a variable phenotypic spectrum with a common aetiology.

The ankyloblepharon-ectodermal defects-cleft lip and palate (Hay-Wells or AEC) and the Rapp-Hodgkin syndrome (RHS) are rare autosomal dominant ectodermal dysplasias due to mutations in the transcription factor gene P63. Both are caused by mutations affecting SAM or TID domains of TP63 protein. The two disorders share common features and may represent different phenotypic expressions of the same clinical entity. To date more than 20 P63 mutations have been described associated with AEC and RHS, the majority of which are missense or nonsense mutations. Molecular heterogeneity cannot account for the clinical heterogeneity, because the same mutations were observed both in patient with RHS and with AEC syndrome. Here we report on a novel P63 mutation (the first repeat variation described in the gene) in a patient showing overlapping phenotype of AEC and RH syndromes.

[Italian guidelines and recommendations for prevention and treatment of pain in the newborn]. / Linee-guida e raccomandazioni per la prevenzione ed il trattamento del dolore nel neonato.

OBJECTIVE: Despite accumulating evidence that procedural pain experienced by preterm infants may have acute detrimental and even long-term effects on an infant's subsequent behavior and neurological outcome, neonates admitted to Neonatal Intensive Care Units still frequently experience acute and prolonged uncontrolled pain. Many invasive and surgical procedures are routinely performed at the bedside in the NICU without adequate pain management. AIM: To develop evidence-based guidelines and recommendations for pain control and prevention in Italian i.e. heel lancing, venipuncture and percutaneous venous line positioning, tracheal intubation, mechanical ventilation, lumbar puncture, chest tube positioning, for certain surgical procedures performed at the NICU, e.g. central venous cutdown, surgical PDA ligation, and cryotherapy, laser therapy for ROP, and for postoperative pain management. CONCLUSION: Adequate pain prevention and management should be an essential part of standard health care at the NICU, and recognizing and assessing sources of pain should be routine in the day-to-day practice of physicians and nurses taking care of the newborn. We hope these guidelines will contribute towards increasing the NICU caregiver's awareness and understanding of the importance of adequate pain control and prevention.

Congenital malformations in twins: an international study.

Data provided by nine registries based in European and Latin America countries were analyzed to assess whether there is an excess of malformations in twins compared to singletons. Specific congenital malformations were coded according to the ninth revision of the International Classification of Diseases (ICD). Malformation rates and rate ratios (RR) for twins compared to singletons were calculated for each registry, and the homogeneity of the RRs was tested using the test of Breslow and Day. If departure from homogeneity in the different registries was not significant, registry-adjusted RRs with 95% confidence intervals were calculated. Overall, among 260,865 twins, 5,572 malformations were reported. A total of 101 different types of malformations or groups of defects was identified, and a homogeneous estimate of the RRs among registries was found for 91.1% of the malformations. Thirty-nine of the 92 malformations with homogeneous estimates of RRs were more common in twins than in singletons. For the remaining nine malformations, heterogeneous estimates of RRs were obtained. This study confirms the majority of already known associations and further identifies previously unreported malformations associated with twins. In conclusion, there is an excess of malformations in twins compared with singletons, and all anatomical sites are involved. The number of specific malformations associated with twins is higher than that previously reported in smaller studies.

Limb defects associated with major congenital anomalies: clinical and epidemiological study from the International Clearinghouse for Birth Defects Monitoring Systems.

Although limb defects associated with other congenital anomalies are rarely studied, they may provide insights into limb development that may be useful for etiologic studies and public health monitoring. We pooled data from 11 birth defect registries that are part of the International Clearinghouse for Birth Defects Monitoring Systems. We identified 666 infants, born from 1983 through 1993, who had a non-syndromal limb defect plus at least one other major malformation (rate 12.9/100,000 population). We used observed/expected ratios and log-linear models to detect association patterns. We found that specific limb defects occurred with relatively distinct sets of malformations. Preaxial limb defects occurred more frequently with microtia, esophageal atresia, anorectal atresia, heart defects, unilateral kidney dysgenesis, and some axial skeleton defects; postaxial defects with hypospadias; transverse defects with craniofacial defects, micrognathia, ring constrictions, and muscular defects; intercalary defects with omphalocele; split hand/foot with encephalocele; and amelia with anorectal atresia, omphalocele, severe genitalia defects, unilateral kidney dysgenesis, gastroschisis, and ring constriction. Log-linear modeling identified higher order associations among some of these same malformations.

The spectrum of congenital anomalies of the VATER association: an international study.

The spectrum of the VATER association has been debated ever since its description more than two decades ago. To assess the spectrum of congenital anomalies associated with VATER while minimizing the distortions due to small samples and referral patterns typical of clinical series, we studied infants with VATER association reported to the combined registry of infants with multiple congenital anomalies from 17 birth defects registries worldwide that are part of the International Clearinghouse for Birth Defects Monitoring Systems (ICB-DMS). Among approximately 10 million infants born from 1983 through 1991, the ICB-DMS registered 2,295 infants with 3 or more of 25 unrelated major congenital anomalies of unknown cause. Of these infants, 286 had the VATER association, defined as at least three of the five VATER anomalies (vertebral defects, anal atresia, esophageal atresia, renal defects, and radial-ray limb deficiency), when we expected 219 (P<0.001). Of these 286 infants, 51 had at least four VATER anomalies, and 8 had all five anomalies. We found that preaxial but not other limb anomalies were significantly associated with any combination of the four nonlimb VATER anomalies (P<0.001). Of the 286 infants with VATER association, 214 (74.8%) had additional defects. Genital defects, cardiovascular anomalies, and small intestinal atresias were positively associated with VATER association (P<0.001). Infants with VATER association that included both renal anomalies and anorectal atresia were significantly more likely to have genital defects. Finally, a subset of infants with VATER association also had defects described in other associations, including diaphragmatic defects, oral clefts, bladder exstrophy, omphalocele, and neural tube defects. These results offer evidence for the specificity of the VATER association, suggest the existence of distinct subsets within the association, and raise the question of a common pathway for patterns of VATER and other types of defects in at least a subset of infants with multiple congenital anomalies.

An international collaborative study of the epidemiology of esophageal atresia or stenosis.

Epidemiologic data were analyzed for a total of 2,693 infants with esophageal atresia registered in nine congenital malformation registries around the world. The average recorded prevalence at birth was 2.6 per 10,000 births, with a significant variability among programs--and sometimes within a program--and a maximum prevalence of above 3 per 10,000 births. Clusters of infants with esophageal atresia were observed but may be random. An increasing rate was seen during the period 1965 to 1975 (Norway, South America, Sweden). The type of esophageal atresia was specified in only 439 cases, but no major differences were seen in the epidemiologic characteristics of infants with the most common type (distal fistula) and infants with other types. There was an excess of low birth weight and preterm birth, and infants with esophageal atresia had a birth weight 500 to 1,000 g less than normal infants in each gestational week. There was an excess of twins, apparently mainly or exclusively due to monozygotic twinning, but in only two pairs did both twins have esophageal atresia. There was no effect seen of maternal age, but low parity, irrespective of maternal age, was associated with an increased risk for esophageal atresia. Infant survival varied among programs and depended heavily on associated malformations. Among 1,107 sibs born before the proband and 385 born after the proband, only 25 (1.7%) had a serious malformation; three had esophageal atresia. In 57.3% of the infants with esophageal atresia, no other malformations were present, in 36.4% other major malformations were recorded, and in 6.3% there were chromosomal anomalies. The malformations present associated with esophageal atresia were analyzed: a large proportion entered the constellation sometimes called "caudal mesoderm spectrum of malformations": VATER, Potter, and caudal regression sequences.

Ultrasonographic appearance of the mega cisterna magna in the newborn.

The mega cisterna magna is a congenital developmental malformation which in the majority of instances is symptomless and does not require further study or surgical treatment. However, differential diagnosis with other cerebellar diseases is often necessary especially in newborn infants. Ultrasonographic recognition of the mega cisterna magna in a newborn infant is reported. The reported case demonstrates the usefulness of the ultrasonographic technique in the study of the posterior cranial fossa abnormalities of newborn infants.

Subband neural networks prediction for on-line audio signal recovery.

In this paper, a subbands multirate architecture is presented for audio signal recovery. Audio signal recovery is a common problem in digital music signal restoration field, because of corrupted samples that must be replaced. The subband approach allows for the reconstruction of a long audio data sequence from forward-backward predicted samples. In order to improve prediction performances, neural networks with spline flexible activation function are used as narrow subband nonlinear forward-backward predictors. Previous neural-networks approaches involved a long training process. Due to the small networks needed for each subband and to the spline adaptive activation functions that speed-up the convergence time and improve the generalization performances, the proposed signal recovery scheme works in online (or in continuous learning) mode as a simple nonlinear adaptive filter. Experimental results show the mean square reconstruction error and maximum error obtained with increasing gap length, from 200 to 5000 samples for different musical genres. A subjective performances analysis is also reported. The method gives good results for the reconstruction of over 100 ms of audio signal with low audible effects in overall quality and outperforms the previous approaches.

Bone pulsating metastasis due to hypernephroma.

Bone pulsating metastasis due to hypernephroma is an exceptional occurrence. The authors present one case of bone pulsating metastasis due to hypernephroma localized in the proximal tibia. The primary renal lesion was located by ultrasonography and confirmed by CT scan.

[Clinico-statistical features of perinatal and early neonatal mortality]. / Rilievi clinico-statistici sulla mortalità perinatale e neonatale precoce.

Perinatal and neonatal mortality rates are considered to be among the most sensitive measures available for monitoring the health of population and consequently have been assumed, too, to reflect primarily the capacity of the obstetricians and pediatricians. Perinatal mortality is here defined as stillbirths (or late fetal deaths) plus early neonatal deaths, that is, it includes fetuses born dead after 28 completed weeks of pregnancy and liveborn infants who died before the completion of the first week after birth. This report is concerned with the variation in neonatal mortality observed at the Istituto Clinico di Puericultura, Bologna University in a period from 1971 to 1981 and in perinatal mortality from 1976 to 1981 only. In this period reductions in stillbirths (from 12.5% to 7.8%) and early neonatal mortality (from 13.2% to 7.0%) are recorded. The decrease in the perinatal mortality rate, which occurred at the Obstretic-Neonatal Unit of Bologna University (dropping from 25.6% in 1976 to 14.8% in 1981) may be attributed to a comparable reduction in stillbirths and early neonatal mortality due to better health services and a more modern pattern of medical care. More attention must be given to that particular group of newborn babies weighing 1,500 gm or less (VLBW Infants) which accounted for about 40% of all the neonatal deaths.

[The Emilia-Romagna Abnormalities Study Group: coverage and geographic distribution of congenital abnormalities in Emilia-Romagna]. / Gruppo I.M.E.R.: copertura e distribuzione geografica delle malformazioni congenite in Emilia-Romagna.

Systems for monitoring Congenital Malformations (C.M.) have been taken up by most Countries, even though there is great diversity in the methods of data collection. In Italy nothing existed until 1977. In 1978 in the Emilia-Romagna Region an epidemiological Program began for the surveillance and monitoring of all C.M. diagnosed in the first 7 days of life in the newborn babies and in the stillbirths of over 28 weeks of gestational age. After three years of monitoring-1978 to 1980-we have reached the baseline data which is the fundamental prerequisite to ensure comparability of data from different centers and within our region in different periods too. The incidence of all C.M. was 1.9% in the first three years of monitoring with no statistical difference from year to year or between the Districts of the Region. For six selected C.M. we studied the incidence in the Region and also in the four Districts starting from 1978. Our data is comparable to that reported in the other Countries but we observed high incidence of Down Syndrome (17.2 per 10,000 births that is one of the highest values detected = 1 case every 582 newborn babies). For hypospadias we observed, starting from the second quarter of 1980, a progressive increase that dropped however in the first quarter of 1981. No etiologic clues have yet been revealed.

[The VACTERL association and its nosologic limits]. / L'associazione V.A.C.T.E.R.L. ed i suoi limiti nosologici.

We present six cases of V.A.C.T.E.R.L. association diagnosed by the Study Group of Congenital Malformations in Emilia Romagna (I.M.E.R.) from january 1978 to december 1981. With regard to the etiology, the pregnancy history of these six cases does not support the hypotesis of the progestin-estrogen compounds as possible teratogenic factors of the V.A.C.T.E.R.L. association. Furthermore the familial recurrence hypotesis of this complex needs further detailed studies. At last we attempt to specify the nosological limits of the V.A.C.T.E.R.L. association respect to other similar malformative complexes as the Caudal Regression Syndrome, Rokitansky Syndrome, Holt-Oram Syndrome and Potter Syndrome.

[Genito-urinary malformations in a regional survey in Emilia Romagna]. / Le malformazioni genito-urinarie nell'indagine regionale dell'Emilia Romagna (I.M.E.R.).

In a multicentric survey carried out in Emilia Romagna area on congenital malformations 1914 babies out of 103484 babies born from 1978-1984 were discovered to have malformations. Out of these malformations cases 17% were found to be affected by genitourinary tract anomalies (GU) divided as follows: 235 genital malformations and 91 urinary tract anomalies. All these GU patients were diagnosed within the first week of life. Genital malformations: Genital malformations are mainly constituted by hypospadias, found in 214 out of 235 babies. Among these babies, 72% have first degree hypospadias, 22.4% have second degree, and only ten babies were found with third degree hypospadias. In this study 4.1 out of 1000 male newborns have been found affected by hypospadias, in agreement with the results of other researches whose values were between 2% and 4.4%. Many different variables (such as parental age, exposure to smoke, alcohol, RX-ray before pregnancy, low birth weight, early age at menarche, exposure to progestins for threatened abortion, shorter gestation) have been considered in order to verify their correlation with the hypospadias, comparing with control group. Among these the most statistically significant are the exposure to progestins for threatened abortion (p less than 0.05), early age at menarche (p less than 0.001) and the intrauterine growth retardation (p less than 0.001). Also these results agree with the previous studies. Urinary tract anomalies: the 93 babies with kidney and-or urinary tract malformations out of 103484 newborns represent the 8.9%. The diagnoses were made or suspected (and later confirmed) during the first week of life.(ABSTRACT TRUNCATED AT 250 WORDS)

[Problems of development and care of children born with selected congenital malformations: Down's syndrome, cardiopathy, cleft lip and palate, clubfoot]. / Problemi dello sviluppo e dell'assistenza di nati con malformazioni congenite selezionate: sindrome di Down, cardiopatia, labiopalatoschisi, piede torto.

In connection with the surveillance programme of congenital malformations in Emilia Romagna led by I.M.E.R. Group since 1978 a crosswise survey has been performed on selected malformations: Down's syndrome, cardiac defects, unilateral or bilateral cleft lip and/or palate, unilateral or bilateral club foot. This survey has been useful as a pilot-study for another longitudinal survey which had a place in the programmes of the C.N.R. (National Research Council). By means of a multi-discipline approach we have collected information both of pediatric and of psycho-social character. A total of 187 children with the above named malformations were recorded at birth, 106 boys and 81 girls, aged from 9 months to 4 years. The neonatal diagnosis was confirmed in 84 out 86 cases under study. The rate of infant mortality was particularly high among children with heart defects (39.1%) and Down children (27.4%). The surgical centres where these children were operated upon, through with large variations in connection with the type of malformation, were in Emilia Romagna (49%), outside it (40%), and abroad (10.9%). As for the parental reaction to the birth of babies with congenital malformations, it was of initial rejection 5 cases of Down children, 3 cases of cardiopathy and 1 case of cleft lip and palate. Later the refusal was permanently confirmed only in 2 cases of Down children (who were subsequently adopted). The birth of a malformed baby has affected the relationship between husband and wife contributing to the separation in 3 cases of Down's syndrome and in 1 case of cardiopathy.

Malformation surveillance and maternal drug exposure: the MADRE project.

A project implemented within the framework of the International Clearinghouse for Birth Defect Monitoring Systems is named MADRE: MAlformation DRug Exposure surveillance. The idea is to survey the simultaneous occurrence of malformations and first-trimester drug exposures. In a 2-year period 1990-91, this has yielded 1448 infants known to have been exposed to drugs and that are known to have malformations. Cases have been reported by eight programs: Australia, Central-East France, Israel, Italy IPIMC, Italy IMER, Japan Red Cross Hospitals, Japan Maternal Health and Welfare, and South America. By searching this databank for associations between drugs and malformations, specific relationships can be detected.The 9th revision of the WHO International Classification of Diseases, adapted by the British Paediatric Association, known as ICD9/BPA is used for coding malformations. This is a hierarchical system with 5 digits as the maximum level of specification of each malformation.The ATC (Anatomical Therapeutic Chemical) classifications system is used for coding drugs. This is a multiple level, hierarchical classification with up to 7 digits for specifying each drug.Up to five drugs and malformations are coded for each case using ATC and ICD9/BPA classifications, and all observed drug-malformation pairs form the basis for the analysis. For each drug-malformation combination where three or more cases are observed, a set of 2×2 tables is formed and analyzed as in case-control studies. The odds ratio for the pair, stratified for program, gives the relative risk for the malformation in question, comparing use of the specific drug with all other drugs.Well known or controversial associations were tested in the collected material, and at this stage only one new association is suggested, that is between cardiac defects and maternal treatment with thyroid hormones. This finding has to be further explored with new data.

Comparison of two different neonatal skin care practices and their influence on transepidermal water loss in healthy newborns within first 10 days of life.

AIM: Physiologic post-partum skin adaptation to the relative dry extra-uterine environment is a dynamic process which begins immediately after birth. Considering the differences from adult skin, the neonatal skin is more prone to damage by environmental factors; therefore, skin care regimens should be age adapted to ensure a good epidermal maturation. The effects of two different skin care practices were evaluated by transepidermal water loss (TEWL) measurement in 94 newborns aged ≤ 10 days: group 1 (G1), newborns washed only with a cotton washcloth moistened with water; group 2 (G2), newborns washed with liquid baby cleansers and hydrated with moisturizers. These recordings were compared to TEWL baseline values of the same neonates and to adults' values. METHODS: A prospective study was conducted in healthy full-term newborns, measuring TEWL with TEWAMETER® TM300. The areas tested were the volar forearm and the popliteal fossa. RESULTS: In G1 (52 subjects), TEWL mean values were 6.65 ± 2.81 SD (g/m2/h) at volar forearm and 7.49 ± 2.47 SD (g/m2/h) at popliteal fossa. In G2 (42 subjects), TEWL mean values were 8.83 ± 3.05 SD (g/m2/h) at volar forearm and 10.18 ± 3.64 SD (g/m2/h) at popliteal fossa. There were statistically significant differences of TEWL mean values between G1 and G2, newborns and adults, baseline and post-skin care procedures. CONCLUSION: Tested skin care regimens could influence the process of functional adaptation of skin, in the early postnatal period. We could hypothesize that daily washing with liquid baby cleansers and moisturizing may delay the natural maturation of skin barrier function.