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.

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.

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.

Prenatal diagnosis of open and closed spina bifida.

OBJECTIVE: To identify criteria useful for differentiating closed from open spina bifida antenatally. PATIENTS AND METHODS: A retrospective study of cases of spina bifida diagnosed in a referral center between 1997 and 2004. RESULTS: Of 66 cases of fetal spina bifida diagnosed at a median gestational age of 21 (range, 16-34) weeks, detailed follow-up was available for 57. Of these, open defects were found in 53 (93.0%) and closed defects in four (7.0%). Closed spina bifida was associated in two cases with a posterior cystic mass with thick walls and a complex appearance, while in two cases the spinal lesion could not be clearly differentiated from an open defect, particularly at mid-gestation. Open spina bifida was always associated with typical alterations of cranial anatomy, including the so-called 'banana' and 'lemon' signs, while in closed spina bifida the cranium was unremarkable. When the data were available, levels of amniotic fluid alpha-fetoprotein were always abnormally elevated with open spina bifida and within normal limits with closed forms. CONCLUSION: In this study 7% of cases of spina bifida diagnosed in utero were closed. The differentiation between open and closed forms is best shown by the sonographic demonstration of abnormal or normal cranial anatomy.

[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 heart defects: 15 years of experience of the Emilia-Romagna Registry (Italy).

OBJECTIVES: Collection and assessment of data from the Emilia-Romagna Region on the occurrence of congenital heart defects in order to identify an homogeneous group of patients for further aetiologic and genetic studies. MATERIALS AND METHODS: The present study is based on 1549 stillborn and live born babies affected by congenital heart defect out of 330,017 consecutive births (4.7 per 1000). RESULTS: The frequency and type of congenital heart defects have been identified together with the sex ratio, associated extracardiac anomalies, chromosomal anomalies and the risk of precurrence in relatives. The impact of prenatal diagnosis on prevalence was low during the study period. CONCLUSIONS: The study has provided epidemiological data for public health surveillance of congenital heart defects in the Emilia-Romagna region. The creation of a system for the nationwide recording of congenital heart defects designed with regard to the sources of ascertainment, the diagnostic criteria, and the system of classification is emphasised.

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.

On the symmetry of limb deficiencies among children with multiple congenital anomalies.

In humans, unpaired organs are placed in a highly ordered pattern along the left-right axis. As indicated by animal studies, a cascade of signaling molecules establish left-right asymmetry in the developing embryo. Some of the same genes are involved also in limb patterning. To provide a better insight into the connection between these processes in humans, we analysed the symmetry of limb deficiencies among infants with multiple congenital anomalies. The study was based on data collected by the International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS). Registries of the ICBDMS provided information on infants who, in addition to a limb deficiency, also had at least one major congenital anomaly in other organ systems. We reviewed 815 such cases of which 149 cases (18.3 %) were syndromic and 666 (81.7 %) were nonsyndromic. The comparisons were made within the associated limb deficiencies, considering the information on symmetry, using a comparison group with malformations associated not involved in the index association. Among the non-syndromic cases, the left-right distribution of limb deficiencies did not differ appreciably between limb deficiency subtypes (e.g., preaxial, transverse, longitudinal). The left-right distribution of limb anomalies did not differ among most types of non-limb anomalies, though a predominance of left-sided limb deficiencies was observed in the presence of severe genital defects - odds ratio [OR], 2.6; 95 % CI, 1.1-6.4). Limb deficiencies (LDs) were more often unilateral than bilateral when accompanied by gastroschisis (OR, 0.1) or axial skeletal defects (OR, 0.5). On the contrary, LDs were more often bilateral than unilateral when associated with cleft lip with or without cleft palate (OR, 3.9) or micrognathia (OR, 2.6). Specifically, we found an association between bilateral preaxial deficiencies and cleft lip, bilateral amelia with gastroschisis and urinary tract anomalies, and bilateral transverse deficiencies and gastroschisis and axial skeleton defects. Of 149 syndromic cases, 62 (41.6 %) were diagnosed as trisomy 18. Out of the 30 cases of trisomy 18 with known laterality, 20 cases were bilateral. In the remainder the right and left sides were equally affected. Also, in most cases (74.4 %) only the upper limbs were involved. In conclusion the left-right distribution of limb deficiencies among some non-limb anomalies may suggest a relationship between the development of the limb and the left-right axis of the embryo.

Teratogenic effects of antiepileptic drugs: use of an International Database on Malformations and Drug Exposure (MADRE).

PURPOSE: The study goal was to assess teratogenic effects of antiepileptic drugs (AEDs) through the use of a surveillance system (MADRE) of infants with malformations. METHODS: Information on all malformed infants (1990-1996) with maternal first-trimester drug exposure was collected by the International Clearinghouse for Birth Defects and Monitoring Systems (ICBDMS). Cases were defined as infants presenting with a specific malformation, and controls were defined as infants presenting with any other birth defect. Exposure was defined by the use of AEDs during the first trimester of pregnancy. The association of AEDs with malformations was then estimated by calculating the odds ratios with 95% confidence intervals and testing their homogeneity among registries. RESULTS: Among 8005 cases of malformations, 299 infants were exposed in utero to AEDs. Of those exposed to monotherapy, 65 were exposed to phenobarbital, 10 to methylphenobarbital, 80 to valproic acid, 46 to carbamazepine, 24 to phenytoin, and 16 to other AEDs. Associations were found for spina bifida with valproic acid. Infants exposed to phenobarbital and to methylphenobarbital showed an increased risk of oral clefts. Cardiac malformations were found to be associated with phenobarbital, methylphenobarbital, valproic acid, and carbamazepine. Hypospadias was associated with valproic acid. Porencephaly and other specified anomalies of brain, anomalies of face, coarctation of aorta, and limb reduction defects were found to be associated with valproic acid. CONCLUSIONS: Using the MADRE system, we confirmed known teratogenic effects of AEDs. We also found increased risks for malformations that had never been reported associated with AEDs or for which the association was suggested by case reports.

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.

[Congenital cardiopathy in a data-based population]. / Le cardiopatie congenite in una popolazione data-based.

Altogether 429.139 consecutive births were surveyed during the eighteen years study period by the Emilia-Romagna Registry. Among these, 2147 newborns with congenital heart defects (CHD) (prevalence 5 per 1000) were detected within the first week of life. There were 1607 isolated CHDs and 540 cases had other associated defects. During the study period an increase in prevalence/rate of CHDs was observed (from 3.1 per 1000 in 1980 to over 7 per 1000 in 1998), particularly isolated CHDs increased from 2.2 to 6 per 1000, while the prevalence rate of CHDs cases with other associated anomalies was constant ranging from 1 to 2 per 1000. The increase of isolated CHDs was due to the increased number of "minor" lesions such as ventricular (VSD) and atrial septal defect. The apparent increase in birth prevalence of CHD mainly results from improved diagnosis due to widespread use of color-doppler ecocardiography. As in other studies, a significant shift in the sex-ratio has been documented: a male predominance in transposition of great arteries, left hypoplastic heart and aortic stenosis (male/female ratio 2.2, 2.3, 4.5 respectively) were found; while VSD had a slight female excess (male/female ratio 0.96). The study confirmed that the majority of the affected parents were mothers. The recurrence risk of a cardiac defect in first degree relatives was 2.3%, while the recurrence risk of isolated conotruncal defects was 3.9%. Out of 47 cases with isolated conotruncal defects 4 had microdeletion of chromosome 22q11.2 and concerning the first degree relatives in one case the father had the deletion without CHD.

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.