ADAM sequence and innocent amniotic band: manifestations of early amnion rupture

Thirteen placentas with early amnion rupture (EAR) are described. These placentas were characterized by the absence of amniotic epithelium on the fetal surface, presence of a slightly fibrotic small amniotic band (remnant) attaching to the umbilical cord at the placental end, and the presence of degenerated vernix squamous cells in the fibrous stroma of chorion and amnion. Eight fetuses had ADAM sequence. Six of these fetuses were miscarried between 16 and 28 weeks of gestation. Two affected infants were born alive at gestational ages of 29 and 39 weeks. Five infants were spared by ADAM sequence; two had the umbilical cord strangulated by an amniotic band and were delivered at 27 and 37 weeks. In the 3 infants unassociated with ADAM sequence or strangulation of the umbilical cord, their placentas were interpreted as having innocent amniotic band (IAB) and they were delivered between 32 and 40 weeks. The findings in this study support Torpin's hypothesis that ADAM sequence is a complication of EAR. This ADAM sequence due to simple EAR must be separated from the limb body wall malformation complex because visceral anomalies are uncommon in the former condition but are frequently seen in the latter. In this study the placental pathology of EAR was helpful in confirming the ADAM sequence in the fetus.     

Septo-optic dysplasia and amniotic bands: further evidence for a vascular pathogenesis

Septo-optic dysplasia (SOD) is a heterogeneous disorder. While most cases represent an isolated defect, SOD has also been seen in association with mutations in single genes, as a part of multiple congenital anomaly syndromes and with exposure to various teratogens. We report a boy with features of SOD who also has limb defects suggestive of amniotic bands. This case, in addition to others in the literature, provides evidence for a vascular pathogenesis of SOD in some individuals. This hypothesis is also supported by the sporadic occurrence of SOD and its association with decreased maternal age, vascular teratogens, and neuropathologic findings suggestive of vascular insults.     

Constrictive amniotic bands,amniotic adhesions,and limb-body wall complex: Discrete disruption sequences with pathogenetic overlap

In a fetopathologic evaluation of 18 cases with amniotic bands, we discerned 3 types of lesions: (1) constrictive tissue bands, (2) amniotic adhesions, and (3) more complex anomaly patterns, designated as limb-body wall complex (LBWC). Constrictive bands are caused by primary amnion rupture with subsequent entanglement of fetal parts (mostly limbs) by shriveled amniotic strands. Adhesive bands are the result of a broad fusion between disrupted fetal parts (mostly cephalic) and an intact amniotic membrane. Most of the craniofacial defects (encephaloceles and/or facial clefts) occurring in these fetuses are not caused by constrictive amniotic bands, but are the result of a vascular disruption sequence with or without cephalo-amniotic adhesion. Our observations confirm the fact that amnion rupture is not a conditio sine qua non for the development of LBWC. However, LBWC is often complicated by rupture of the unsupported amnion with ensuing formation of constrictive bands. We think that the concept that considers the 3 lesions in question as a single pathogenetic entity is erroneous and will inevitably lead to a never-ending debate between followers of the 2 prevailing theories. In our view, the theories of Streeter and Torpin are not mutually exclusive but rather apply to different types of lesions. The recognition of constrictive amniotic bands, amniotic adhesions, and LBWC as discrete but often combined disruption sequences with important pathogenetic overlap may resolve many dilemmas in interpretation when a fetus exhibits classical constrictive bands beside more severe defects.     

Constrictive amniotic bands, amniotic adhesions, and limb-body wall complex: discrete disruption sequences with pathogenetic overlap.

In a fetopathologic evaluation of 18 cases with amniotic bands, we discerned 3 types of lesions: (1) constrictive tissue bands, (2) amniotic adhesions, and (3) more complex anomaly patterns, designated as limb-body wall complex (LBWC). Constrictive bands are caused by primary amnion rupture with subsequent entanglement of fetal parts (mostly limbs) by shriveled amniotic strands. Adhesive bands are the result of a broad fusion between disrupted fetal parts (mostly cephalic) and an intact amniotic membrane. Most of the craniofacial defects (encephaloceles and/or facial clefts) occurring in these fetuses are not caused by constrictive amniotic bands, but are the result of a vascular disruption sequence with or without cephalo-amniotic adhesion. Our observations confirm the fact that amnion rupture is not a conditio sine qua non for the development of LBWC. However, LBWC is often complicated by rupture of the unsupported amnion with ensuing formation of constrictive bands. We think that the concept that considers the 3 lesions in question as a single pathogenetic entity is erroneous and will inevitably lead to a never-ending debate between followers of the 2 prevailing theories. In our view, the theories of Streeter and Torpin are not mutually exclusive but rather apply to different types of lesions. The recognition of constrictive amniotic bands, amniotic adhesions, and LBWC as discrete but often combined disruption sequences with important pathogenetic overlap may resolve many dilemmas in interpretation when a fetus exhibits classical constrictive bands beside more severe defects.     

Noneosinophilic asthma: a distinct clinical and pathologic phenotype

The use of induced sputum to assess airway inflammation in large and diverse populations with asthma has led to the recognition that significant numbers of patients do not have evidence of eosinophilic airway inflammation. The absence of a sputum eosinophilia has been noted in patients across the range of asthma severity; it has also been reported in patients presenting with an asthma exacerbation. However, whether noneosinophilic asthma represents a pathologically distinct and clinically important asthma phenotype remains unclear. In this review, we present recent evidence suggesting that noneosinophilic asthma represents a stable phenotype associated with a distinct lower airway pathology and structure. We suggest that this lower airway inflammation develops in response to etiologic factors acting through the innate immune pathway and that elements of this immune response contribute to airway dysfunction. Finally, we argue that noneosinophilic asthma is associated with clinically important differences in natural history and treatment response. We particularly highlight evidence that noneosinophilic asthma is associated with a reduced short-term and long-term response to corticosteroid therapy.     

49,XXXXY: a distinct phenotype. Three new cases and review.

Over 100 cases of 49,XXXXY syndrome have been published to date. Classic findings include radioulnar synostosis, hypogonadism, and mental retardation. The majority of reported cases have not distinguished the 49,XXXXY syndrome from Klinefelter syndrome (47,XXY), and these patients are frequently labelled as having Klinefelter syndrome or as being a "Klinefelter variant." Because of distinct clinical features, we delineate the 49,XXXXY syndrome as separate from Klinefelter syndrome, and emphasise the prevalence of congenital heart defects. We also report three new cases of 49,XXXXY syndrome and briefly discuss patient management.     

New treatment for band keratopathy: superficial lamellar keratectomy, EDTA chelation and amniotic membrane transplantation

We report two cases of band keratopathy who were treated with thick amniotic membrane that contained a basement membrane structure as a graft, after ethylenediaminetetraacetic acid chelation with trephination and blunt superficial lamellar keratectomy in the anterior stroma. In each case, basement membrane was destroyed and calcium plaque invaded into anterior stroma beneath Bowman's membrane. The calcified lesions were removed surgically, resulting in a smooth ocular surface, and the fine structures of band keratopathy were confirmed by pathologic findings. After that, amniotic membrane transplantation was performed to replace the excised epithelium and stroma. Wound healing was completed within 10 days. Stable ocular surface was restored without pain or inflammation. During the mean follow-up period of 13.5 months, no recurrence of band keratopathy was observed. This combined treatment is a safe and effective method for the removal of deep-situated calcium plaque and allowing the recovery of a stable ocular surface.     

Development of gap junctions in hippocampal astrocytes: evidence that whole cell electrophysiological phenotype is an intrinsic property of the individual cell

Gap junction communication between astrocytes is prevalent and has been proposed to be involved in several astrocyte functions. One such proposal involves gap junctions in potassium spatial buffering. However, little is known about the developmental time course of gap junction coupling and how much the syncytium affects whole cell measurements of ion currents. Our previous work described three types of hippocampal astrocyte, each with a distinct electrophysiological profile when recorded in whole cell voltage-clamp mode. In the current study we correlated post-whole cell recording immunohistochemistry for GLAST and the spread of injected dye from the recorded cell with the measured electrophysiological phenotype to quantify cell coupling of astrocytes and the type of astrocyte coupled, in the rat hippocampus. We found that passive astrocytes, which predominate after 3 wk postnatally, have much lower membrane resistances (Rm) and are more frequently dye coupled and to more cells, than outwardly and variably rectifying astrocytes that predominate in early postnatal development. Dye coupling in GLAST(+) cells was first detected in the first postnatal week and the degree of coupling peaked before the complete transition to the low Rm, passive electrophysiological type. Also, the degree of dye coupling did not correlate with the passive electrophysiological phenotype. Passive cells were also detected after pretreatment with a gap junction inhibitor. Further evidence that cell coupling does not contribute to the mature astrocyte electrophysiological phenotype came from recording of excised membrane patches, which predominantly corresponded to the ion channel expression profiles of their cells of origin. These findings imply that in the hippocampus, interastrocyte cell coupling likely contributes little to the overall whole cell current profile of diverse glia, and the electrophysiological passivity reflects the intrinsic ion channel expression of the mature astrocyte.     

Macrocephaly,distinct craniofacial appearance,and spastic paraplegia: a new case and expansion of the phenotype

An adult female patient is presented with macrocephaly, mental retardation, seizures, spastic paraplegia and distinctive craniofacial appearance. We believe she represents the fourth case of the Fryns macrocephaly, distinct craniofacial appearance and spastic paraplegia syndrome. Cardinal features are discussed and additional phenotypic manifestations are discussed.     

p.L18P: a novel IDUA mutation that causes a distinct attenuated phenotype in mucopolysaccharidosis type I patients

Mucopolysaccharidosis type I is a rare autosomal recessive disorder caused by deficiency of α‐l ‐iduronidase (IDUA) which leads to a wide spectrum of clinical severity. Here, we describe the case of four male patients who present the previously undescribed p.L18P mutation. Patient 1 (p.L18P/p.L18P) presents, despite multiple joint contractures, an attenuated phenotype. Patient 2 (p.L18P/p.W402X) was diagnosed at 4 years of age with bone dysplasia, coarse facies, limited mobility, claw hands and underwent bilateral carpal tunnel surgery at 6 years of age. Patients 3 and 4 (both p.L18P/p.L18P) are brothers. Patient 3 was diagnosed at 4 years of age, when presented claw hands, lower limb and shoulder pain, restricted articular movement and bilateral carpal tunnel syndrome. Patient 4 was diagnosed at 17 months of age when presented lower limb pain at night, respiratory allergy and repeated upper airways infections. Bioinformatics analysis indicates that p.L18P mutation reduces the signal peptide to 25 amino acids and alters its secondary structure. In conclusion, we report a new IDUA variant that alters the structure of the signal peptide, which likely impairs transport to lysosomes. Moreover, it leads to a distinct attenuated phenotype with mainly bone and cartilage symptoms, without visceromegalies, heart disease, or cognitive impairment.     

Amniotic band sequence and limb defects: Data from a population-based study

Cases with amniotic bands were analysed separately as part of an ongoing study of limb defects occurring among 1,213,913 liveborn infants in British Columbia during the years 1952 to 1984. A total of 24 cases with this specific condition was identified among 659 cases with limb defects. The calculated incidence for amniotic band sequence with significant limb involvement was 0.19 in 10,000 livebirths. This is a minimal incidence, as cases without defects of the limbs, but with constriction rings were not identified with this approach. Familial cases and cases with additional anomalies were found. © 1993 Wiley-Liss, Inc.     

Stellate transformation of invasive trophoblast: a distinct phenotype of trophoblast that is involved in decidual vascular remodelling and controlled invasion during pregnancy

BACKGROUND: Successful implantation relies on the tightly regulated invasion of extravillous trophoblasts (EVTs). However, little is known about their phenotypic differentiation and relevant motile behaviour. Furthermore, the cell-cell interactions between EVTs and decidual arterioles during physiological transformation are also poorly understood. METHODS: A total of 128 decidual specimens from early and late gestations containing components of EVTs and spiral arterioles were investigated using immunohistochemistry and periodic acid-Schiff reaction. RESULTS: Unipolar, tadpole-like EVTs are observed throughout the interstitial area, with a tendency to decrease along the invasive pathway. The stellate differentiation of the EVTs is identified around and inside decidual arterioles or in the third-trimester myometrium. Furthermore, stellate transformation of EVTs precedes its interactions with the decidual arteriole. These specialized stellate trophoblasts invade and infiltrate the tunica media, accompanying lacuna formation inside the vessel wall and perturbation of actin fibre alignment of the tunica media. CONCLUSION: Stellate transformation of trophoblasts may explain controlled invasion of EVTs and probably plays a key role in initiating cell-cell interaction in decidual vascular remodelling.     

MAN1B-CDG: Novel variants with a distinct phenotype and review of literature

Background

Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases due to impaired lipid and protein glycosylation. It comprises a characteristic high frequency of intellectual disability (ID) and a wide range of clinical phenotypes.

Ectopic pancreas, intussusception, and a ruptured mesenteric band: an unusual association

Although ectopic pancreas and intussusception are not unusual conditions, intussusception caused by ectopic pancreas is extremely rare. Its presence along with a ruptured congenital mesenteric vascular band raises the possibility of an anomaly of the vitelline vascular system. We report the case of a 26-year-old man presenting with acute abdominal pain, vomiting, and diarrhea. CT scan showed a large amount of free fluid in his abdomen and an ileo-ileal intussusception. At laparotomy he was found to have hemoperitoneum with a ruptured, actively bleeding congenital band attached to the ileal mesentery, which was ligated, with ileo-ileal intussusception that was resected. Histopathology showed ectopic pancreatic tissue as the lead point for the intussusception. It was likely to be a ruptured mesodiverticular band and along with other findings suggested a constellation of anomalies of the vitello-intestinal tract.     

Tricho-hepato-enteric syndrome: Further delineation of a distinct syndrome with neonatal hemochromatosis phenotype,intractable diarrhea,and hair anomalies

We report on two sibs with syndromal congenital iron storage disease. Prenatal symptoms were IUGR, hydramnios, and placental hyperplasia. Clinical anomalies included hypertelorism and sparse, thin, curly hair (trichomalacia). Clinical course was marked by intractable diarrhoea, with normal histological and enzymological studies, cholestatic jaundice, hepatomegaly appearing after 30 days, and progressive liver failure, leading to death after a few months. The only metabolic anomaly was progressive hypermethioninemia. Pathologic examination of both children showed a similar pattern of multivisceral iron deposit compatible with a diagnosis of neonatal hemochromatosis: extensive liver fibrosis or cirrhosis with nodular regeneration, cholestasis, ductular proliferation, and hepatic, pituitary, thyroidal, adrenal, and pancreatic iron deposition. The unusual course for neonatal hemochromatosis in both sibs combined with concordant extrahepatic anomalies suggest that they could have a specific iron storage syndrome with possible autosomal recessive inheritance, probably similar to the sibship reported by Stanckler et al. [Arch Dis Child, 57:212–216, 1982]. Am. J. Med. Genet. 68:391–395, 1997. © 1997 Wiley-Liss, Inc.     

Body stalk defects, body wall defects, amniotic bands with and without body wall defects, and gastroschisis: comparative epidemiology

The presence of body wall defects with "evisceration" of thoracic and/or abdominal organs associated with other congenital anomalies, with or without limb deficiencies, is considered to be the body wall complex (BWC). The BWC is different from gastroschisis, which is usually a small body wall defect lateral to the umbilical cord that is not covered by any membrane and, in most of the cases, is an isolated defect. For the present analysis we separated the BWC group into three subgroups. One group was that of body stalk anomalies characterized by severe defects of the abdominal wall with absence of, or very small, umbilical cord, or this is continuing with the placenta. The second group was made up of those infants with body wall defects without amniotic bands, and the third group was of those children with body wall defects produced by amniotic bands. We considered two additional groups in the analysis, one was of infants with gastroschisis and the other those infants with amniotic bands without body wall affectation. We also included the control group (nonmalformed infants) for comparisons. From the results of our epidemiological study, we can conclude that amniotic bands with body wall affectation and amniotic bands without body wall defects are two different entities. The results also suggest that the characteristics of infants with amniotic bands with body wall defects are more similar to the group of infants with body stalk anomalies. This may indicate that the former group is produced during the very early gestation.     

Crossed polydactyly type I in a mother and son: an autosomal dominant trait?

In a Japanese family, a propositus and his mother had crossed polydactyly type I. A maternal grandaunt also had preaxial polydactyly of the feet. The findings that both of the mother and son had the identical type of polydactyly are consistent with an autosomal dominant inheritance with variable expressivity. Other explanations include X-linked recessive inheritance, polygenic inheritance, and a chance occurrence of the 2 different kinds of polydactyly.