Pituitary gland and sella turcica in human trisomy 18 fetuses

The purpose of this study was to elucidate the phenotypic conditions in the sella turcica/pituitary gland complex in human trisomy 18 fetuses. Fourteen human fetuses with gestational ages from 12 to 39 weeks were included in the study. Normal fetuses at corresponding ages were used as controls. Whole body and special radiographic examination was undertaken before the midsagittal cranial base block, including the pituitary gland, was excised and analyzed histologically and immunohistochemically (keratin wide spectrum [KWS], thyroid-stimulating hormone [TSH], and neurophysin [Nph]). In all trisomy 18 fetuses, TSH-positive adenopituitary tissue was present in the sella and in greater or lesser amounts pharyngeally. The neurohypophysis was Nph-positive and located normally in the sella turcica. The adenohypophyseal tissue reacted either KWS-faint or KWS-negative, whereas KWS-positive reaction occurs in normal fetuses. This circumstance might suggest an altered cytoskeletal structure of the surface ectoderm in the pituitary placode in trisomy 18. The sella turcica was malformed in all the fetuses. Very broad craniopharyngeal canals were observed in some of the fetuses. Because endocrine disorders occur in many congenital malformations, it is essential in future studies to chart the sella turcica/pituitary gland region systematically in different genotypes. Am. J. Med. Genet. 76:87–92, 1998. © 1998 Wiley-Liss, Inc.     

Postnatal structure of the sella turcica in Down syndrome

The purpose of this study was to analyze the shape of the sella turcica in a group of patients with Down syndrome and compare the findings with those made earlier in human fetuses with Down syndrome. Profile radiographs from 78 patients (age 4 months to 50 3/12 years) were analyzed. A tracing was made of each sella turcica, and the shape was compared with that of a normal sella, including the normal growth pattern from childhood to adulthood. Sella turcica structure could be classified into three morphological types, defined as: type I, almost normal appearance; type II, deviations in the anterior wall; and type III, deviations in the floor of the sella turcica. Compared with previously registered prenatal structural deviations in the sella turcica, it can be concluded that the postnatal radiographic material reflects the prenatal findings, because type I, both prenatally and postnatally, is by far the most common, whereas the remaining types are uncommon, both prenatally and postnatally. The study confirms the relevance of prenatal investigations for postnatal diagnostics as previously documented in sella turcica analyses of prenatal and postnatal myelomeningocele cases. Am. J. Med. Genet. 87:183–188, 1999. © 1999 Wiley-Liss, Inc.     

A reappraisal of the hypophysial region of the floor of the sella turcica

While studying the detailed anatomy of the cranial sella turcica, an additional fossa in its floor, which has not previously been described, was noted. A survey for this fossa, therefore, was conducted on 205 adult crania from the Raymond A. Dart Collection of Human Skeletons, University of the Witwatersrand. To confirm the survey observations, the sella turcica region of 10 adult cadavers was also dissected. A larger anterior depression and a smaller posterior concave fossa, often extending on to the anterior surface of the dorsum sellae, were evident in the hypophysial region and occurred in 21.5% of crania and in six of the 10 dissected specimens. An anterior depression alone or a posterior fossa alone occurred in 2.4% and in 72% of the crania, respectively, indicating that the posterior fossa occurs most commonly in this series. The more commonly occurring presence of a posterior fossa abutting on to the anterior surface of the dorsum sellae is described for the first time.     

Pattern of malformations in the axial skeleton in human trisomy 21 fetuses

In the present study, we analyzed the development of the axial skeleton in human trisomy 21 fetuses and defined the fields in the axial skeleton affected in this form of aneuploidy. We investigated 31 human fetuses with trisomy 21, gestational ages 12–24 weeks, on the basis of radiographs of midsagittal tissue blocks of the axial skeleton, comprising the cranial base and the spine. Malformation or agenesis of the nasal bone was present in 19 of 31 fetuses. Nineteen cases had vertebral malformations. Fourteen fetuses had malformations in the cervical region, four in the thoracic and eight in the lumbosacral region. In 1 of 31 fetuses, malformation was seen in the basilar part of the occipital bone. The basisphenoid component appeared scallop-shaped in 30 cases. The pattern of axial skeletal malformations in trisomy 21 fetuses recorded here has not been described previously. Comparison is made with our recent study of trisomy 18, where the pattern of axial skeletal malformations was quite different. It is recommended that axial skeletal radiography should be part of the autopsy of fetuses where chromosome abnormalities are known or suspected. Am. J. Med. Genet. 68:466–471, 1997. © 1997 Wiley-Liss, Inc.     

Relationship between the development of diaphragma sellae and the morphology of the sella turcica and its content

Summary The impaired formation of the diaphragma sellae may lead to the development of the empty-sella syndrome. This structure, when fully formed, is a protective barrier against the pulsating action that the cerebrospinal fluid exerts on the sellar content. There are anatomical features which support this belief, but they also suggest that the development of the diaphragma sellae is a factor which determines the morphology of the sella turcica and its contents. Those human specimens which do not have diaphragma sellae or in which it is only partially developed, are characterized by a smaller hypophysis, always located at the inferior and/or posterior half of the sella, with a larger sellar volume and frequently greater fragility of its bony walls. These findings, although rare (5% of the cases), are indirect signs of the important role which the diaphragma sellae plays in the sellar region.

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Rapports entre la formation du diaphragme sellaire et la morphologie de la selle turcique et de son contenu

Résumé Le développement incomplet du diaphragme sellaire peut être à l'origine d'un syndrome de la selle turcique vide. Lorsque ce diaphragme est bien formée, il constitue une barrière efficace, protégeant le contenu de la selle turcique de la pression pulsatile du liquide cérébro-spinal. Des études anatomiques semblent corroborer ces données et suggèrent même que le développement du diaphragme sellaire conditionne la morphologie de la selle turcique et son contenu. C'est ainsi que l'on peut observer chez certaines personnes dont le diaphragme sellaire est absent ou partiel, l'existence d'une petite glande pituitaire qui est toujours plaquée à la partie inférieure et/ou postérieure de la selle turcique ; de surcroit, le volume de la selle est augmenté et ses parois osseuses sont plus fragiles qu'à l'accoutumée. Tous ces faits, bien que rares (5% des cas), établissent de façon indirecte le rôle important que joue le diaphragme sellaire sur la région pituitaire.

     

Hand development in trisomy 21

The purpose of the present study was to evaluate hand size and maturity in fetuses with trisomy 21 (Down syndrome). Twenty-five fetuses, crown-rump length (CRL) 55–222 mm, foot length (FL) 8–42 mm, were included in the study. After whole-body radiography (Hewlett Packard Faxitron), special radiographs of the hand and foot were taken. Hand length was measured as the length of the third finger from the distal tip of the distal phalanx to the proximal tip of the metacarpal bone, the digital-metacarpal length (DML). The lengths of the proximal phalangeal bone (PPL) and the metacarpal bone (MCL) of the third finger were also measured. The DML, PPL, and MCL values of each fetus were related to CRL and FL. The individual hand bones were evaluated with regard to time of appearance on radiographs, sequence in comparison with the normal sequence of appearance, and morphology. The hand length is normal during the first half of the fetal period, whereas the length of individual bones in the third finger is reduced. The normal sequence of ossification, with the middle phalanx of the fifth finger last to ossify, also occurred in Down syndrome; however, this bone appeared later in Down syndrome. In four of the fetuses it did not appear (CRLs: 125, 158, 172, and 174 mm). Am. J. Med. Genet. 79:337–342, 1998. © 1998 Wiley-Liss, Inc.     

Increased nuchal translucency in trisomy 21 fetuses: relationship to narrowing of the aortic isthmus

Pathological examination of the great vessels was performedin 34 trisomy 21 fetuses after surgical termination of pregnancyat 11–16 weeks of gestation. In each case, the externaldiameters of eight segments of the great vessels were measured.The aortic valve and the ascending aorta were wider than innormal fetuses, whilst the aortic isthmus was narrower. Thedegree of narrowing of the isthmus was significantly greaterin fetuses with high nuchal translucency thickness and it ispossible that there is a causal association between the two.     

Pattern of malformations in the axial skeleton in human trisomy 18 fetuses

We examined and described the development and abnormalities of the axial skeleton in 10 human trisomy 18 fetuses. Whole-body radiographs and radiographs of midsagittal tissue blocks of the cranial base and the spine were studied. In 3 fetuses no spinal radiographs were available. Seven osseous regions or fields along the body axis were analyzed, four in the spine, and three in the cranial base and nasal bones. Malformations occurred in the occipital field in all fetuses. This was a characteristic notching, either unilateral or bilateral, of the basilar part of the occipital bone. Nasal bones were abnormal in 8 cases, either absent or hypoplastic. Malformations were found in the thoracic and/or lumbosacral field in 7 fetuses. A single abnormality was found in the cervical spine in one fetus. The pattern of axial skeletal malformation in trisomy 18 fetuses recorded in the present study has not been described previously. Axial skeletal radiography should be included in autopsies of fetuses when chromosome disorders are present or suspected. The methods applied here are unaffected by autolysis. © 1996 Wiley-Liss, Inc.     

Pituitary choristoma composed of corticotrophs and adrenocortical cells in the sella turcica

A pituitary tumour composed of well-differentiated corticotrophs and adrenocortical cells is reported. Sections of the tumour revealed a mixture of small round cells with amphophilic or basophilic periodic acid-Schiff (PAS)-positive cytoplasm and large spherical and oval cells with abundant, granular, partly vacuolated PAS-negative cytoplasm. The small cells contained type 1 cytokeratin-positive microfilaments, numerous 250–500 nm endocrine-type secretory granules immunoreactive for adenocorticotropic hormone (ACTH) and -lipotropin. The large cells possessed ample cytoplasm filled with abundant vesicular smooth endoplasmic reticulum, numerous mitochondria possessing tubulovesicular cristae and frequent dense bodies. They lacked the features of pituitary endocrine cells or folliculostellate cells and were found to contain a panel of steroidogenic dehydrogenases and hydroxylases. The tumour was classified as a choristoma, in which two distinct cells types, corticotrophs and adrenocortical cells, were mixed. We suggest that, under continued ACTH stimulation, uncommitted stem cells may differentiate into adrenocortical cells. Alternatively, the presence of adrenocortical cells may be the result of heterotopia.     

Copper/zinc superoxide dismutase (SOD-1) activity in regular trisomy 21, trisomy 21 by translocation and mosaic trisomy 21

Cu/Zn superoxide dismutase (SOD-1) (E.C.1.15.1.1.) activity was estimated in children with regular trisomy 21-Down syndrome as well as in cases of translocation and mosaic trisomy 21, as identified by the GTG, CBG and RHG banding techniques. SOD-1 activity was found to be increased in all examined cases except trisomy 21 mosaicism. These findings provide further proof of the gene dosage theory and additional biochemical evidence for the triplicate existence of the SOD-1 gene localized on chromosome 21     

Skeletal anomalies in trisomy 21 as an example of amplified developmental instability in chromosome disorders: Histological study of the feet of 21 mid-trimester fetuses with trisomy 21

In a previous radiographic study on the feet of 71 adults with trisomy 12 we found, in comparisn to control individuals, an increased prevalence of biphalangeal toes and metatarsophalangeal sesamoid bones. The present histological study on the feet of 21 mid-trimester fetuses with prenatally diagonosed trisomy 21 confirms results of the earlier study. At both stages of development these minor bone anomalies have about the same frequency, thus suggesting 1) that they are selectively neutral, and 2) that they reflect a basic (innate) failure of ordered morphogenesis. Our observation that the normal spatial pattern skeletal variants is reproduced in trisomy 21 simply on a quantitavely higher level lends sound support to the hopothesis of amplified developmental instability in chromosome trisomies.     

Dermatoglyphic and cytogenetic studies in parents of children with trisomy 21

Dermatoglyphic studies were carried out of 131 mothers and 95 fathers of children with Down syndrome and 200 controls (100 males and 100 females) using the Hopkins single score method. Twelve percent of the mothers and 2% of the fathers showed dermatoglyphic abnormalities including a distal axial triradius (t"), hypothenar ulnar loops, radial loops on digits IV and V and abnormal palmar creases, resulting in a positive Hopkins score or a score in the "overlapping range" (greater than -3). The origin of the extra chromosome could be determined in 23 of a total group of 40 families. In 22 of the former, the mother was the donor of the extra chromosome; in one it was the father, In these 23 families, a Hopkins score in the overlapping range was found in three mothers who were all under the age of 35 years at the birth of the affected child. Since cytogenetic studies cannot easily differentiate between meiotic nondisjunction and mosaicism as a basis for 21 trisomy in the progeny, it is possible that mothers with positive overlapping Hopkins scores represent undetected mosaics for a trisomic cell line. The dual approach utilizing dermatoglyphic and cytogenetic studies may aid in identifying persons with an enhanced risk for having children with Down syndrome.     

Catalase and glutathione peroxidase activity in cells with trisomy 21

CuZnSOD is produced in overdose in cells with trisomy 21. This has been considered to be a cause of increased oxidative stress. In the present work we have studied the catalase and glutathione peroxidase activity in fibroblasts from 6, and blood cells from 30, subjects affected by Down syndrome. In the fibroblasts, catalase and glutathione peroxidase activities did not differ significantly from control cells. In platelets, lymphocytes, polymorphs and erythrocytes, no significant increase of catalase activity was found while glutathione peroxidase activity appeared significantly increased in platelets, polymorphs and erythrocytes but not in lymphocytes. These data seem to indicate that the increase of CuZnSOD in trisomy 21 cells does not affect the production of catalase. An increase, instead, of glutathione peroxidase has been detected in all blood cells, except in lymphocytes; this is a sign of a greater need for protection against the risk of lipoperoxidation. The fact that the enhancement of glutathione peroxidase activity could be assessed only in some types of cells examined suggests that the observed increase in those cells is probably a result of an additive effect of the overproduction of CuZnSOD due to gene dosage and the ordinarily higher content of oxygen radicals and peroxides.     

济宁农村地区21三体综合征致家庭负担调查研究

目的了解21三体综合征致农村家庭负担,为今后降低21三体综合征对家庭的危害性提供依据。方法对2009年1月至今前来检查并确诊的125名21三体综合征患者的家庭陪成员（陪护人）进行调查,并结合GQOLI量表,对21三体综合征患者家庭陪护人生活、精神状况进行调查研究。结果绝大多数21三体综合征患者家庭支付的当年医疗费用均高于当年收入;通过对其陪护人生活质量调查发现：21三体综合征患者家庭陪护人在GQOLI量表的4个维度的评分均低于同地区普通农村人口,差别有统计学意义（P〈0.01）。结论 21三体综合征作为一种常见的出生缺陷,在严重影响患者自身生命质量的同时,给农村家庭造成的经济和精神负担均不容忽视。     

Tertiary trisomy due to a reciprocal translocation of chromosomes 5 and 21 in a four‐generation family

Tertiary trisomy, or double trisomy, is a rare occurrence. We present two individuals with a previously unreported tertiary trisomy for chromosomes 5p and 21q in an eight‐generation pedigree. Their phenotypes are compared with other partial trisomies of either 5p or 21q from the literature. The propositus was diagnosed with trisomy 21 at 2 years of age after a karyotype study for short stature and developmental delay. His phenotype was described as atypical for Down syndrome. He presented at 9 years of age because of pervasive behavioral problems and obesity. He was brachycephalic with a flattened nasal bridge, but he lacked other characteristics of trisomy 21. Because of lack of phenotypic evidence of Down syndrome, a repeat karyotype was obtained and showed 47,XY,+der(21)t(5;21)(p15.1; q22.1), incorporating partial trisomies of both chromosomes 5 and 21. Mother had a balanced translocation, 46,XX,t(5;21)(p15.1; q22.1); 8 other relatives were examined. The translocation originated from the maternal great‐grandmother, but only the propositus and his mentally retarded aunt had a similar phenotye and the derivative chromosome. Fluorescence in situ hybridization showed absence of band 21q22.2 in the derivative chromosome of the propositus and his aunt, indicating that neither had trisomy for the Down syndrome critical region. These cases represent a unique double partial trisomy of chromosome arms 5p and 21q that occurred because of 3:1 malsegregation of a reciprocal translocation. These cases further demonstrate that phenotypic discordance with cytogenetic results dictate further investigation using advanced cytogenetic hybridization. Am. J. Med. Genet. 92:311–317, 2000. © 2000 Wiley‐Liss, Inc.     

Collagen type VI expression during cardiac development and in human fetuses with trisomy 21

The role played by specific extracellular matrix molecules in normal endocardial cushion differentiation into valves and septa remains to be established. In this respect, type collagen VI is of particular interest because genes encoding the alpha1 and alpha2 chains are located on chromosome 21, and defects involving the atrioventricular (AV) cushions are frequent in trisomy 21. Collagen VI expression was studied in normal human embryonic and fetal hearts (5-18 weeks of development) and compared by immunohistochemistry with results from fetuses (10-16 weeks of development) with trisomy 21. During normal endocardial cushion differentiation (5-8 weeks) there was marked collagen VI expression in the AV cushions, whereas only minor expression was seen in the outflow tract cushions. In the normal fetuses (10-18 weeks), collagen VI in the AV cushions had condensed into a marked zone on the atrial side of the leaflets, as well as subendocardially in other regions of high shear stress. Morphological defects involving the endocardial cushion-derived structures were present in all trisomy 21 cases. An abnormally large membranous septum was observed in three cases. An AV septal defect (AVSD) was present in two, while one had a ventricular septal defect (VSD). Two cases presented with a secondary atrial septal defect (ASDII), and one had an AVSD. Mild to moderate valve dysmorphia was found in all cases. Collagen VI staining in trisomy 21 was more intense than in the normal subjects; however, there were no differences in the spatial expression patterns. We conclude that collagen VI is expressed in the AV cushions and persists during valve differentiation. Collagen VI is more prominent in fetal trisomy 21 hearts than in normal hearts. We hypothesise that collagen VI has a role in the development of heart defects involving endocardial cushion differentiation-specifically in the AV canal, the most common site of malformations affecting children with trisomy 21.     

Rapid prenatal diagnosis of trisomy 21 by real-time quantitative polymerase chain reaction with amplification of small tandem repeats and S100B in chromosome 21

Trisomy 21 (Down syndrome) is the most common congenital anomaly, and it occurs in one out of 700-1000 births. Current techniques such as amniocentesis and chorionic villi sampling (CVS) require lengthy laboratory culture procedures and high costs. This study was undertaken to establish a rapid prenatal diagnosis of trisomy 21 using real-time quantitative polymerase chain reaction (PCR) of fetal DNA from amniotic fluid. Real-time quantitative PCR was performed with DNA templates obtained from 14 normal blood samples, 10 normal amniotic fluid samples, 14 Down syndrome blood samples, and 7 Down syndrome amniotic fluid samples. Primers for D21S167 and S100B of chromosome 21 were used. Primers that direct the amplification of the 165-bp fragment of the insulin-like growth factor (IGF)-1 gene on chromosome 12 using a PCR primer were included to generate an internal standard for quantitation. The relative levels of D21S167 and S100B were 2.6 and 2.4 times higher in the blood of Down syndrome patients than those in the control group. The differences between these two groups were statistically significant (p-values were 0.0012 and 0.0016, respectively). The relative levels of D21S167 and S100B were 2.1 and 2.7 times higher in the amniotic fluid of Down syndrome fetuses than those in the control group. The difference between these two groups was statistically significant (p-values were 0.0379 and 0.0379, respectively). Prenatal diagnosis of trisomy 21 by real-time quantitative PCR using STR (small tandem repeats) amplification of D21S167 and S100B is a useful, accurate and rapid diagnostic method. Furthermore, it may also be useful for prenatal diagnosis with fetal DNA from maternal blood, and for preimplantation genetic diagnosis and prenatal counseling.     

胎儿味腺发育与一氧化氮合酶阳性表达的关系

目的：探讨人胎儿味腺发育与一氧化氮合酶(NOS)阳性表达的规律。方法：用NADPH—d组织化学法对人多组胎龄胎儿味腺NOS阳性表达进行观察。结果：胎4月初,舌上皮组织呈较强的NOS阳性反应,在轮廓乳头环沟处,上皮基底细胞向深部组织增生,形成许多上皮细胞条索,细胞条索NOS阳性反应随胎龄增加而增强,上皮条索生长迅速,向深部肌肉组织不断增长发支,分支的末端膨大成腺泡,起初腺泡数目较少,NOS阳性反应较弱。随着胎龄的增加,腺泡数目增多,NOS阳性反应逐渐增强,至胎6月时达到高峰。胎7～9月时,味腺导管增粗,腺泡体明显增大。接近成熟状态,NOS反应呈强阳性。胎10月时,味腺导管和腺泡细胞NOS阳性反应减弱。结论：胎儿味腺发育与NOS阳性表达密切相关。