Skeletal and cardiac malformations with thrombocytopenia: A new syndrome?

We describe a female patient with multiple anomalies suggestive of a new syndrome. Manifestations include: VSD and ASD, mild developmental delay, conductive hearing loss, minor facial anomalies, thrombocytopenia, and radiological findings (including carpal fusion). Some of these manifestations may be present in the Keutel syndrome, IVIC syndrome, and the 10qter deletion syndrome. However, none of these syndromes can explain the spectrum of anomalies seen in our patient. © 1996 Wiley-Liss, Inc.     

西罗莫司治疗淋巴管畸形的研究进展

头颈部淋巴管畸形可能造成毁容,诱发功能性合并症,甚至危及生命.手术及药物治疗淋巴管畸形有一定效果,但复杂淋巴管畸形仍然是临床治疗难点.西罗莫司是哺乳动物雷帕霉素靶蛋白的抑制剂,可减少内皮细胞血管内皮生长因子的生成,调节血管生成、细胞增殖、迁移和粘附,在淋巴管成熟和稳定中发挥关键作用.近年临床研究提示该药物在治疗复杂淋巴...     

Multiple vascular malformation in the 'blue rubber bleb naevus' syndrome: a case with aneurysm of vein of Galen and vascular lesions suggesting a link to the Weber–Osler–Rendu syndrome

A case of Bean's syndrome is reported in which a wide variety of vascular malformations are illustrated. Among these were multiple arterio-venous malformations including a so-called vein of Galen aneurysm. A comparison of this case with those in the literature suggests that the pathology in patients with Bean's syndrome may be more varied than heretofore recognized, and that an overlap between this syndrome and the Osler–Weber–Rendu syndrome may exist.     

Patterns in multimalformed babies and the question of the relationship between sirenomelia and VACTERL

Starting from a data base of over one million births investigated in 11 countries as a part of the Latin American Study of Congenital Malformations, 1,428 babies with three or more malformations without known pathogenesis or cause were studied. The objective was to search for statistically significant associations between defects and the delineation of new syndromes. One hundred and twentyone patients presented an association between malformations of the digestive and urogenital systems involving mainly anal, renal, and genital anomalies, while 21 of them had 3 or more VACTERL defects. The frequencies of these defects were intermediate between those observed for VACTERL or sirenomelia, supporting the idea that these conditions have a similar pathogenesis. Statistical approaches like this one may be helpful in identifying processes and biological entities that may be missed using simple clinical observations. © 1994 Wiley-Liss, Inc.     

Avoid diagnostic delay of late infantile and juvenile neuronal ceroid-lipofuscinosis (LINCL,JNCL): A word to pediatricians,neurologists, and ophthalmologists

We describe a large family with congenital microtia, auditory meatal atresia and conductive deafness. The pedigree suggests autosomal dominant inheritance with variable expression and low penetrance. The literature is also reviewed to describe the inheritance pattern and clinical spectrum noted in this rare syndrome so far. The family is unique because the set of otologic anomalies in five generations was associated with renal cysts in one of the affected members, suggesting that this oto-renal (OR) syndrome may represent a variable expression of the branchio-oto-renal (BOR) syndrome. However, the probability is that this dominant malformation syndrome is a distinct entity. © 1995 Wiley-Liss, Inc.     

Cutaneous findings of familial cerebral cavernous malformation syndrome due to the common Hispanic mutation

Familial cerebral cavernous malformations due to the common Hispanic mutation (FCCM1‐CHM) is an endemic condition among the Hispanic population of the Southwestern United States associated with significant morbidity and mortality. Cutaneous vascular malformations (CVMs) can be found in individuals with FCCM1‐CHM, but their morphology, prevalence, and association with cerebral cavernous malformations (CCMs) has not been well characterized. A cross‐sectional study of 140 individuals with confirmed FCCM1‐CHM was performed with statistical analyses of CVM, CCM, and patient characteristics. We then compared these findings to other cohorts with Familial cerebral cavernous malformations (FCCM) due to other mutations. We observed a higher overall prevalence and a different predominant morphological subtype of CVM compared to previous FCCM cohorts. While the number of CVMs was not a reliable indicator of the number of CCMs present, each person with one or more CVMs had evidence of central nervous system (CNS) disease. Awareness of the morphology of these cutaneous lesions can aid in the diagnosis of individuals with FCCM‐CHM in Hispanic patients or those with family history of CCM.     

Absent ulna in the Klippel-Feil syndrome: an unusual associated malformation

A patient is reported with a severe type 2 Klippel-Feil syndrome, and absent ulna and ulnar ray. The severity of the musculo-skeletal involvement did not allow for corrective procedures. This uncommon association of skeletal malformations has not been previously reported. Since this syndrome has been described in families as a possible autosomal recessive trait, a 25 % recurrence risk and the possibility of prenatal detection by fetal visualization methods should be taken into consideration.     

A human embryo of 28 mm crown-rump length with cerebral, esophagotracheal and cardiovascular malformations

The following malformations were observed in a human embryo of 28 mm crown-rump length obtained at operation for tubal rupture in a case of extrauterine pregnancy: 1. Secondary anophthalmia with dysplasia and in part aplasia of the diencephalon. Rudiments of both eyes and eyestalklike proliferations within the diencephalon. No lenses and on the left side only a palpebral fissure. Hypoplasia of the right telencephalic hemisphere and of the right side of diencephalon, mesencephalon and proximal parts of the medulla oblongata. Pseudotumorous proliferations in the diencephalon, in the alar plate of the medulla oblongata (protruding into the fourth ventricle) and in the arachnoid. Hypoplasia of the right internal, middle, and external ear. Dysplasia and in part aplasia of facial osseous elements (cebocephalia). 2. Proximal esophageal atresia with distal tracheoesophageal fistula. 3. A Fallot's tetralogy with right-sided aortic arch and regressive right-sided ductus arteriosus, tricuspid atresia, hypoplasia of the right ventricle with excessive hypertrophy of its wall, and hypoplasia of the pulmonary trunk. Single left superior vena cava and abnormal, semicircular course of the stems of both coronary arteries.     

The birth rate of hypospadias in the Turku area in Finland

Reports based on national registers of congenital malformations have suggested that the birth rate of hypospadias has increased during the last few decades. Register-based information may, however, have pitfalls because of changes in diagnostics, reporting accuracy and registration system. The aim of this study was to determine the current birth rate of hypospadias in Turku University Central Hospital (TUCH) in Finland. This was a prospective study on live-born boys born in TUCH from 1997 to 1999. In the total birth cohort (n=5,798) as well as in a special subcohort group (n=1,505) 0.3% of boys had hypospadias. Only one scrotal hypospadias was found in a boy who had a chromosomal anomaly. Other hypospadias were glandular or coronal. No increase was found in the birth rate of hypospadias when comparing our result with register-based data of boys born in Finland during the years 1970 to 1986 and surgically treated for hypospadias by the age of 8 years. No difference was found either from malformation register-based data concerning the nationwide birth rate of hypospadias during the years 1993 to 1998. Due to differences in national registration systems between countries, prospective studies with equal assessment criteria are needed in order to make reliable international comparisons.     

XX-agonadism in a fetus with multiple dysraphic lesions: A new syndrome

We report on a 19-week-old fetus with a 46,XX karyotype, normal female external genitalia, complete gonadal agenesis, large encephalocele, spina bifida, and omphalocele. We postulate a new syndrome. Hitherto no consistent malformation patterns have been observed in agonadism patients. True agonadism, including even the unusual finding of an XX gonosomal status, is obviously not as rare as suggested. Am. J. Med. Genet. 70:413–414, 1997. © 1997 Wiley-Liss, Inc.     

Variation in severity of cardiac disease in Holt-Oram syndrome

We describe a family with Holt-Oram syndrome (HOS) with variable hand and cardiac manifestations. One affected relative had complex congenital malformations of the heart consisting of an endocardial cushion defect and hypoplasia of the left ventricle. The literature from 1974 to 1995 is reviewed. Atrial septal defect is the most common cardiac abnormality (60.3% of 189 cases) occurring singly or in combination with other malformations. Thirty-three individuals (17.5% of literature cases) have more complex congenital malformations of the heart requiring complicated medical management and extensive cardiac surgery. Many genetic reference sources of HOS indicate that single or less severe cardiac malformations are expected in this disorder. It is important to provide more information about the occurrence and spectrum of severity of malformations of the heart to individuals and families where HOS is present. © 1996 Wiley-Liss, Inc.     

Non-cardiac malformations in individuals with outflow tract defects of the heart: The Baltimore-Washington infant study (1981–1989)

In the Baltimore-Washington Infant Study, a regional case-control study of 4,390 liveborn infants with cardiovascular malformations (CVM), 642 patients (14.2%) had outflow tract abnormalities, with extracardiac defects in 157 (～25%) of them. Associated defects were found in 1/3 of patients with normal great arteries, but only in 1/10 of patients with transposition of great arteries (TGA). The extracardiac defects were especially rare in the groups “TGA with intact ventricular septum” and “TGA with ventricular septal defect.” Patients with multiple associated defects outnumbered patients with isolated associated defects in the ratio 2.5:1. The associated defects were heterogeneous: 46 patients had chromosome abnormalities, 16 had different Mendelian syndromes, and 36 had associations (DiGeorge sequence and VACTERL association were the most frequent). A new syndrome of multiple congenital abnormalities including tetralogy of Fallot, and rare cases of chromosomal and Mendelian syndromes (distal trisomy 1q, tetrasomy 8p, Holzgreve syndrome) are described briefly. Sufficient variability of a spectrum of conotruncal defects in the patients with the same chromosomal or Mendelian syndromes suggests that at least in some cases different conotruncal defects are stages of the same morphologic spectrum. The analysis of conotruncal defects in sibs of patients with Mendelian syndromes may provide new data about the links between different definitive forms of CVM. © 1995 Wiley-Liss, Inc.     

Proximal deletion of chromosome 21 confirmed by in situ hybridization and molecular studies

Foetal blood sampling was performed at 35 weeks of gestation due to abnormal foetal ultrasound findings. There was apparent monosomy 21 (45,XX,-21) in all mitoses analyzed. The infant died at 37 weeks during delivery. Examination disclosed facial anomalies, clubfeet, hypoplasia of the left urogenital tract, agenesis of corpus callosum, ventricular dilatation, and heterotopias. Reevaluation of the karyotype showed an unbalanced translocation t(1;21) (q44;q22.11) which resulted from a maternal balanced translocation. These findings were confirmed by fluorescence in situ hybridization and molecular studies with chromosome 21 specific markers. The latter showed a proximal deletion of the maternally derived chromosome 21 including all loci from centromere down to the D21S210 locus. This case illustrates the need for complementary cytogenetic and molecular investigations in cases of apparent monosomy 21. © 1994 Wiley-Liss, Inc.     

Congenital testicular lymphangiectasis in children with otherwise normal testes

Two cases of testicular lymphangiectasis are reported, occurring in stillborns. The disease is a congenital malformation consisting of an abnormal expansive development of lymphatic vessels in both testes. Autopsy study revealed the absence of pulmonary, intestinal or systemic lymphangiectasis. The testes showed normal tubular development with normal germ cell numbers and also normal Leydig cell numbers. The epididymis and spermatic cord appeared normal. In contrast with the two previously reported cases of testicular lymphangiectasis, the present cases were not associated with cryptorchidism or other malformations.     

Teratogenetic periods for the principal malformations of the central nervous system

Summary The teratogenetic periods of the most important CNS malformations are defined and briefly discussed. The results are presented in a synoptic figure.The present study is based on the analysis of normal CNS development and on morphogenetic interpretations of the pertinent anomalies. The data compiled from the literature concerning normal development are presented in an analytical table and are also summarized in a synoptic figure.Formerly Fellow of the Alexander von Humboldt Foundation     

无脑儿与多发性畸形

本文观察了143例无脑儿,有88例合并多发性畸形,占61.54%,男女之比为1:2.1.合并二脏器以上畸形者有47例;三脏器以上者41例。其中合并有颅面及骨骼系、呼吸系、消化系、心血管系、泌尿生殖系及隔的畸形等。说明在胚胎发生中,中枢神经系的发育与其他器官的发育密切相关。     

Why study human limb malformations?

Congenital limb malformations occur in 1 in 500 to 1 in 1000 human live births and include both gross reduction defects and more subtle alterations in the number, length and anatomy of the digits. The major causes of limb malformations are abnormal genetic programming and intra-uterine disruption to development. The identification of causative gene mutations is important for genetic counselling and also provides insights into the mechanisms controlling limb development. This article illustrates some of the lessons learnt from the study of human limb malformation, organized into seven categories. These are: (1) identification of novel genes, (2) allelic mutation series, (3) pleiotropy, (4) qualitative or (5) quantitative differences between mouse and human development, (6) physical and teratogenic disruption, and (7) unusual biological phenomena.     

Incidence of congenital malformations in children born after ICSI

The aim of this study was to determine the incidence of congenital malformations in a complete cohort of children born after intracytoplasmic sperm injection (ICSI). The medical records were retrieved for 1139 infants, 736 singletons, 200 sets of twins and one set of triplets. The total number of infants with an identified anomaly was 87 (7.6%), 40 of which were minor. The incidence of malformations in children born after ICSI was also compared with all births in Sweden using data from the Swedish Medical Birth Registry and the Registry of Congenital Malformations. For ICSI children, the odds ratio (OR) for having any major or minor malformation was 1.75 [95% confidence interval (CI) 1.19-2.58] after stratification for delivery hospital, year of birth and maternal age. If stratification for singletons/twins was also done, the OR was reduced to 1.19 (95% CI 0.79-1.81). The increased rate of congenital malformations is thus mainly a result of a high rate of multiple births. The only specific malformation which was found to occur in excess in children born after ICSI was hypospadias (relative risk 3.0, exact 95% CI 1. 09-6.50) which may be related to paternal subfertility.     

FamiIial vascuIar malformations Report of 25 members of one family

Vascular malformations are described in 25 members of one affected family. Most of these lesions were cavernous hemangiomas, but arteriovenous malformations and capillary hemangiomas were also microscopically observed in some specimens. The five generation pedigree suggests the vascular malformations are genetically determined on the basis of a dominant inherited trait.