Epidemiologic characteristics of amniotic band sequence with limb malformations without body wall defect: data from the Polish Registry of Congenital Malformations

Abstract Amniotic Band Sequence (ABS) is a rare disruptive condition, with a variable spectrum of congenital defects caused by fibrous bands emerging as a result of amniotic rupture in the first trimester of gestation. Several factors, such as young parental age, primigravidity, febrile maternal illness, and drug use in the first trimester, were postulated to have substantial influence on ABS prevalence rate. We aimed our study to determine the prevalence of ABS with limb defects, but no body wall affectation, in a Polish population. We also examined the influence of different parental, gestational and environmental factors on the ABS prevalence value, and assessed the rate of gestational complications associated with this disorder. Among 1 706 639 births surveilled between 1998 and 2005, 36 liveborn infants with ABS-L were reported to the Polish Registry of Congenital Malformations, giving a global prevalence for a Polish population of 1 per 47 619 livebirths. We found that young maternal age, young paternal age, and primigravidity significantly increase the risk of ABS-L, when their effect was analyzed independently. However, because of a close relationship of these variables, we analyzed their mutually adjusted effect using conditional logistic regression models, and found that young maternal age proved the strongest risk factor for ABS-L (p = 0.0508). The condition was also more prevalent in infants with low birthweight (OR = 5.71; p < 0.0001). Since gestational complications are often relevant to maternal age and birth order, we introduced an adjustment for these variables, and found that respiratory tract infections and vaginal bleeding/spotting convey approximately fourfold increased risk of ABS-L (OR = 3.72/p = 0.0058 and OR = 3.70/p = 0.0014 respectively)

Frequency of 22q11.2 microdeletion in children with congenital heart defects in western poland

<p>Abstract</p> <p>Background</p> <p>The 22q11.2 microdeletion syndrome (22q11.2 deletion syndrome -22q11.2DS) refers to congenital abnormalities, including primarily heart defects and facial dysmorphy, thymic hypoplasia, cleft palate and hypocalcaemia. Microdeletion within chromosomal region 22q11.2 constitutes the molecular basis of this syndrome. The 22q11.2 microdeletion syndrome occurs in 1/4000 births. The aim of this study was to determine the frequency of 22q11.2 microdeletion in 87 children suffering from a congenital heart defect (conotruncal or non-conotruncal) coexisting with at least one additional 22q11.2DS feature and to carry out 22q11.2 microdeletion testing of the deleted children's parents. We also attempted to identify the most frequent heart defects in both groups and phenotypic traits of patients with microdeletion to determine selection criteria for at risk patients.</p> <p>Methods</p> <p>The analysis of microdeletions was conducted using fluorescence <it>in situ </it>hybridization (FISH) on metaphase chromosomes and interphase nuclei isolated from venous peripheral blood cultures. A molecular probe (Tuple) specific to the <it>HIRA (TUPLE1, DGCR1</it>) region at 22q11 was used for the hybridisation.</p> <p>Results</p> <p>Microdeletions of 22q11.2 region were detected in 13 children with a congenital heart defect (14.94% of the examined group). Microdeletion of 22q11.2 occurred in 20% and 11.54% of the conotruncal and non-conotruncal groups respectively. Tetralogy of Fallot was the most frequent heart defect in the first group of children with 22q11.2 microdeletion, while ventricular septal defect and atrial septal defect/ventricular septal defect were most frequent in the second group. The microdeletion was also detected in one of the parents of the deleted child (6.25%) without congenital heart defect, but with slight dysmorphism. In the remaining children, 22q11.2 microdeletion originated <it>de novo</it>.</p> <p>Conclusions</p> <p>Patients with 22q11.2DS exhibit wide spectrum of phenotypic characteristics, ranging from discreet to quite strong. The deletion was inherited by one child. Our study suggests that screening for 22q11.2 microdeletion should be performed in children with conotruncal and non-conotruncal heart defects and with at least one typical feature of 22q11.2DS as well as in the deleted children's parents.</p

Mowat-Wilson syndrome : growth charts

Background Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of theZEB2gene. It is characterized by moderate-severe intellectual disability, epilepsy, Hirschsprung disease and multiple organ malformations of which congenital heart defects and urogenital anomalies are the most frequent ones. To date, a clear description of the physical development of MWS patients does not exist. The aim of this study is to provide up-to-date growth charts specific for infants and children with MWS. Charts for males and females aged from 0 to 16 years were generated using a total of 2865 measurements from 99 MWS patients of different ancestries. All data were collected through extensive collaborations with the Italian MWS association (AIMW) and the MWS Foundation. The GAMLSS package for the R statistical computing software was used to model the growth charts. Height, weight, body mass index (BMI) and head circumference were compared to those from standard international growth charts for healthy children. Results In newborns, weight and length were distributed as in the general population, while head circumference was slightly smaller, with an average below the 30th centile. Up to the age of 7 years, weight and height distribution was shifted to slightly lower values than in the general population; after that, the difference increased further, with 50% of the affected children below the 5th centile of the general population. BMI distribution was similar to that of non-affected children until the age of 7 years, at which point values in MWS children increased with a less steep slope, particularly in males. Microcephaly was sometimes present at birth, but in most cases it developed gradually during infancy; many children had a small head circumference, between the 3rd and the 10th centile, rather than being truly microcephalic (at least 2 SD below the mean). Most patients were of slender build. Conclusions These charts contribute to the understanding of the natural history of MWS and should assist pediatricians and other caregivers in providing optimal care to MWS individuals who show problems related to physical growth. This is the first study on growth in patients with MWS.Peer reviewe

Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care

Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.MethodsIn a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.ResultsAll anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.ConclusionKnowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.221

Phenotype and genotype of 87 patients with Mowat–Wilson syndrome and recommendations for care

Purpose: Mowat–Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype–phenotype correlations of MWS. Methods: In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations. Results: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluati

History of Research into Causes of Intellectual Disability

Niepełnosprawność intelektualna, dotycząca 2-3% populacji ogólnej krajów Europy Zachodniej, jest istotnym problemem medycznym i społecznym. Praca przedstawia historię badań nad niepełnosprawnością intelektualną: XIX-wieczne teorie, oparte na obserwacji klinicznej, konsekwencje ruchu eugenicznego pierwszej połowy XX wieku i dynamiczny rozwój genetyki, umożliwiający obecnie prowadzenie badań podłoża upośledzenia umysłowego na poziomie cząsteczki DNA.Mental retardation, concerning 2-3% of the general population in Western countries, is a serious medical and social problem. The paper presents the history of studies concerning mental retardation: the early theories based on clinical observations, the consequences of eugenic t ideology and a dynamic progress in medical genetics that provided tools for investigating the causes of mental retardation at the level of DNA molecule

Motor stereotypes

Stereotypie ruchowe (SR) definiowane są jako ruchy mimowolne, o określonym wzorcu, są powtarzalne, skoordynowane, rytmiczne i nieodruchowe. Oprócz nieprowokowanego charakteru tych zaburzeń ważną cechą różnicującą stereotypie ruchowe od fenomenów padaczkowych, jest możliwość natychmiastowego przerwania wykonywania określonej czynności stereotypowej pod wpływem bodźca czuciowego lub na skutek rozproszenia uwagi pacjenta. SR mogą mieć prostą lub złożoną symptomatologię, mogą być pierwotne lub wtórne. W pracy scharakteryzowano SR, przedstawiono przykłady ich występowania, podstawy rozpoznawania w oparciu o aktualne kryteria, diagnostykę różnicową oraz propozycje terapeutyczne.Motor stereotypes (MS) are defined as involuntary movements with a specific pattern, repetitive, coordinated, rhythmic and non-reflexive. In addition to the unprovoked nature of these motor disorders, an important feature that differentiates MS from epileptic phenomena is the ability to immediately stop performing a specific stereotypical activity under the influence of a sensory stimulus or as a result of distraction of the patient. MS can have simple or complex symptomatology, primary or secondary. The paper characterizes SR, presents examples of their occurrence, basics of diagnosis based on current criteria, differential diagnosis and therapeutic proposition