Background Although the medical complications associated with multiple-gestation pregnancies have been well documented, little is known about the effects of such pregnancies on the use of health care resources and the associated costs. This is an important issue because of the increasing use of assisted-reproduction techniques, which commonly result in multiple-gestation pregnancies. Methods We determined hospital charges and the use of assisted-reproduction techniques (such as induction of ovulation, in vitro fertilization, and gamete intrafallopian transfer) for 13,206 pregnant women (11,986 with singleton pregnancies, 1135 with twin pregnancies, and 85 with more than two fetuses) who were admitted for delivery to Brigham and Women's Hospital, Boston, in 1986 through 1991 and their 14,033 neonates (11,671 singletons, 2144 twins, and 218 resulting from higher-order multiple gestations). Results After we controlled for variables known to affect hospital charges, the predicted total charges to the family i...

https://www.nejm.org/doi/pdf/10.1056/NEJM199407283310407

The Economic Impact of Multiple-Gestation Pregnancies and the Contribution of Assisted-Reproduction Techniques to Their Incidence

According to the classification of Osathanondh and Potter of cystic kidneys we give an overview of the different types of cystic changes taking genetic aspects into account. Usually pathoanatomic types do not represent genetic entities: All type I kidneys are transmitted in an autosomal recessive way with varying clinical symptoms; in rare cases they even present in adults. The relationship to "congenital hepatic fibrosis", "cystic liver", and to the "Caroli syndrome" is discussed. Type II kidneys are usually not genetic in origin; but they may occur as part of several syndromes. Rarely genetic factors might contribute to type II kidneys that may present as familial cases of Potter syndrome ("renal non-function syndrome"). Type IV kidneys, although different in their pathoanatomic picture can be regarded according to a common pathogenetic theory as part of the spectrum of malformations as in type II. Therefore the genetic interpretation of type II kidneys also applies to type IV lesions. Type III kidneys include autosomal dominant polycystic kidney disease. This type may already present in childhood; the first prenatal diagnosis by ultrasonography is described in detail. Furthermore type III changes are part of syndromes or non-hereditary malformation complexes, and often present only as mild manifestations. Diseases with isolated involvement of the medulla (juvenile nephronophthisis/medullary cystic disease) or cortex are described as part of the differential diagnosis, they are heterogeneous and genetically only partly understood. Syndromes with cystic kidneys are reviewed as well as the possibilities of prenatal diagnosis of cystic diseases. Reliable prenatal diagnosis is only possible in type II, and possible in some of the other types. The nosology is improved if genetic information is taken into account.

Cystic kidneys. Genetics, pathologic anatomy, clinical picture, and prenatal diagnosis

Nager syndrome, first described more than 60 years ago, is the archetype of a class of disorders called the acrofacial dysostoses, which are characterized by craniofacial and limb malformations Despite intensive efforts, no gene for Nager syndrome has yet been identified In an international collaboration, FORGE Canada and the National Institutes of Health Centers for Mendelian Genomics used exome sequencing as a discovery tool and found that mutations in SF3B4, a component of the U2 pre-mRNA spliceosomal complex, cause Nager syndrome After Sanger sequencing of SF3B4 in a validation cohort, 20 of 35 (57%) families affected by Nager syndrome had 1 of 18 different mutations, nearly all of which were frameshifts These results suggest that most cases of Nager syndrome are caused by haploinsufficiency of SF3B4 Our findings add Nager syndrome to a growing list of disorders caused by mutations in genes that encode major components of the spliceosome and also highlight the synergistic potential of international collaboration when exome sequencing is applied in the search for genes responsible for rare Mendelian phenotypes

Haploinsufficiency of SF3B4, a component of the pre-mRNA spliceosomal complex, causes Nager syndrome.

Objective. Although many pediatricians pursue renal ultrasonography when patients are noted to have external ear malformations, there is much confusion over which specific ear malformations do and do not require imaging. The objective of this study was to de- lineate characteristics of a child with external ear malfor- mations that suggest a greater risk of renal anomalies. We highlight several multiple congenital anomaly (MCA) syndromes that should be considered in a patient who has both ear and renal anomalies. Methods. Charts of patients who had ear anomalies and were seen for clinical genetics evaluations between 1981 and 2000 at Cedars-Sinai Medical Center in Los Angeles and Dartmouth-Hitchcock Medical Center in New Hampshire were reviewed retrospectively. Only pa- tients who underwent renal ultrasound were included in the chart review. The literature was reviewed for the epidemiology of renal anomalies in the general popula- tion and in MCA syndromes with external ear anomalies. We defined a child as having an external ear anomaly when he or she had any of the following: preauricular pits and tags; microtia; anotia; or cup, lop, and other forms of dysplastic ears. A child was defined as having a renal anomaly if an ultrasound revealed any of the fol- lowing: unilateral or bilateral renal agenesis; hypoplasia; crossed ectopia; horseshoe, pelvic, cystic kidney; hydro- nephrosis; duplicated ureters; megaureter; or vesico- ureteric reflux. Results. Because clinical genetics assessments were made by the same clinician at both sites (J.M.G.), data were combined. A total of 42 patients with ear anomalies received renal ultrasound; 12 (29%) of them displayed renal anomalies. Of the 12 patients with renal anomalies, 11 (92%) also received a diagnosis of MCA syndrome. Eleven of 33 patients (33%) with MCA syndromes had renal anomalies, whereas 1 of 9 patients (11%) with iso- lated ear anomalies had renal anomalies. Specific disor- ders seen were CHARGE association, Townes-Brocks syndrome, branchio-oto-renal syndrome, Nager syn- drome, and diabetic embryopathy. Conclusions. We conclude that ear malformations are associated with an increased frequency of clinically sig- nificant structural renal anomalies compared with the general population. This is due to the observation that auricular malformations often are associated with spe- cific MCA syndromes that have high incidences of renal anomalies. These include CHARGE association, Townes- Brocks syndrome, branchio-oto-renal syndrome, Nager syndrome, Miller syndrome, and diabetic embryopathy. Patients with auricular anomalies should be assessed carefully for accompanying dysmorphic features, includ- ing facial asymmetry; colobomas of the lid, iris, and retina; choanal atresia; jaw hypoplasia; branchial cysts or sinuses; cardiac murmurs; distal limb anomalies; and imperforate or anteriorly placed anus. If any of these features are present, then a renal ultrasound is useful not only in discovering renal anomalies but also in the diag- nosis and management of MCA syndromes themselves. A renal ultrasound should be performed in patients with isolated preauricular pits, cup ears, or any other ear anomaly accompanied by 1 or more of the following: other malformations or dysmorphic features, a family history of deafness, auricular and/or renal malforma- tions, or a maternal history of gestational diabetes. In the absence of these findings, renal ultrasonography is not indicated. Pediatrics 2001;108(2). URL: http://www. pediatrics.org/cgi/content/full/108/2/e32; external ear, re- nal, anomalies, ultrasound.

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Syndromic Ear Anomalies and Renal Ultrasounds

Familial aggregates of the most common disorders of mullerian differentiation in females—Mullerian aplasia, incomplete Mullerian fusion—are best explained on the basis of polygenic/multifactorial inheritance. No information exists on the number and chromosomal location of responsible genes. Single mutant genes (Mendelian) are responsible for the McKusick-Kaufman syndrome (MKS) and the hand-foot-genital syndrome. The molecular basis for the latter condition involves HOXA13, but the molecular basis of MKS and other disorders of the female reproductive ducts is unknown. Vaginal atresia, Mullerian aplasia, and incomplete Mullerian fusion are not infrequently observed in malformation syndromes. Am. J. Med. Genet. (Semin. Med. Genet.) 89:224–239, 1999. © 2000 Wiley-Liss, Inc.

Genetics of the female reproductive ducts

We report four patients with Nager acrofacial dysostosis (AFD) syndrome and review all previous cases. This leads to an extended characterization of the Nager syndrome—eg, description of lower limb defects—and also to a discussion of the differential diagnosis which includes AFD postaxial defect syndrome, Fontaine syndrome, distal 2q duplication syndrome, hemifacial microsomia/Goldenhar radial defect syndrome, and some others.

Differential diagnosis of Nager acrofacial dysostosis syndrome: Report of four patients with Nager syndrome and discussion of other related syndromes

We report two female sibs, with severe split-hand/split-foot malformation associated with renal and genital anomalies. The patients also have severe mandibular hypoplasia and some other, minor anomalies. The relationship to the acro-renal "syndrome" in particular and to other phenotypes with similar malformations in general is discussed. Because of consanguinity in the parents, autosomal recessive inheritance seems likely. However, the presence of a septate uterus in the mother and a double collecting system in the only living sib could also suggest possible dominant inheritance with variable expressivity.

Acro‐renal‐mandibular syndrome

Four hundred and thirty-four twins delivered from 220 women at Notre-Dame Hospital were studied during a period of 11 years (1969-1979). The maternal, fetal, and neonatal outcome was compared before and after 1974, the year ultrasonography and other changes in perinatal care were introduced in our institution. Early diagnosis occurred more frequently after 1974, together with increased antenatal hospitalization. Preeclampsia and hepatic cholestasis occurred in 19.5% and 9.5% of women, respectively. Preterm delivery occurred in 42.2% of the cases. The corrected fetal mortality rate was 30.2/1,000 and corrected perinatal mortality rate was 74.9/1,000. About 90% of the neonatal deaths occurred in infants born before 36 weeks. Internal version and complete extraction of the second twin increased the neonatal mortality sixfold compared to spontaneous delivery. Availability of ultrasound examination significantly reduced preterm delivery.

Obstetrical profile of twin pregnancies: a retrospective review of 11 years (1969-1979) at Hôpital Notre-Dame, Montréal, Canada.

Four hundred and thirty four twins occurring in 220 women were studied during a period of 11 years (1969-1979) at Notre-Dame Hospital. Perinatal mortality (less than 28 days) was compared before and after 1974, and the impact of ultrasound technique upon perinatal outcome was assessed during the second period (1974-1979). The main factor associated with perinatal mortality was low birth weight caused by either prematurity or intrauterine growth retardation. While fetal mortality remained unchanged within the two study periods, neonatal mortality decreased from 68.2/1,000 to 28.9/1,000 mainly due to increased survival rate of twins below 1,500 g at birth. With identical perinatal care during the same period, perinatal mortality and incidence of intrauterine growth-retarded twins remained unchanged despite early diagnosis by ultrasound.

Desgranges Mf

Papers

Differential diagnosis of Nager acrofacial dysostosis syndrome: Report of four patients with Nager syndrome and discussion of other related syndromes

Acro‐renal‐mandibular syndrome

Obstetrical profile of twin pregnancies: a retrospective review of 11 years (1969-1979) at Hôpital Notre-Dame, Montréal, Canada.

Perinatal profile of twin pregnancies: a retrospective review of 11 years (1969-1979) at Hôpital Notre-Dame, Montréal, Canada.

Dominant inheritance of nose pits