[Congenital structural defects in twins: diversity, etiology and genetic counseling].
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Abortion, Spontaneous↗
Biomedical subjects
A Schinzel
Publications and source records attributed to A Schinzel.
Recurrent mutation pressure does not explain the prevalence of the marker (X) syndrome.
In order to test the hypothesis that the high prevalence of the mar(X) syndrome is caused by a high mutation rate in male germ cells only, the fraction of new mutants among mothers of probands in 112 informative families has been examined by segregation analysis among their brothers and sisters. The estimated fraction of new mutants among these mothers is much lower than expected if a stable equilibrium existed between an unusually high mutation rate and a selective disadvantage of mentally retarded, male and female mar(X) carriers. Hence, the above-mentioned hypothesis could not be confirmed.
Female↗
Developmental and behavioural disturbances in 13 boys with fragile X syndrome.
Developmental and behavioural aspects were studied in 13 boys aged 2.6-12.5 years from three families with the fragile X syndrome. The following observations were made. Moderate to severe retardation was present in all boys; non-verbal IQs ranged between 25 and 67 (mean 46 +/- 14); IQ and age were negatively correlated (P less than 0.01). Language development was grossly delayed in all boys; most had severe articulation problems. Imitative and symbolic play (e.g. doll play) were strikingly retarded as compared to abstract play (e.g. block design). Autistic features such as no use of eye contact, stereotyped movements and echolalia were found in 9/13 boys; the same number showed aggressive behaviour. General activity was reduced during the 1st year of life; most boys became very hyperactive during the second year; and short attention span and increased distractability were observed in all. Motor development was mildly delayed; all boys were clumsy and moderately hypotonic. The fragile X syndrome ought to be considered in retarded boys with a dissociated developmental pattern, in particular a striking delay in language and play development, and autistic features.
Child↗
[Etiology and pathogenesis of congenital physical and mental handicaps].
Two to five percent of newborn infants present with congenital structural defects. This incidence contains mostly rare to extremely rare conditions. Aetiologically, these consist of defects secondary to genetic and environmental causes, with a third group of defects which are presumed to be due to an unfavorable combination of genetic and environmental factors. In many individual patients, however, allocation into one of these groups is difficult or even impossible. The following clinical and epidemiologic observations may help in some cases to arrive at a classification; pedigree, pregnancy history (infections, teratogens, bleeding, foetal movements etc.), clinical picture and various complementary investigations. Pathogenetically, we may classify congenital structural defects into primary defects (malformations) and secondary ones, if a primarily correctly formed structure has secondarily been deformed (deformation) or destroyed (disruption). In many cases, these clinical observations will then allow a classification into one of the groups. The importance of the determination of the aetiology and pathogenesis of structural defects for the individual family is in the subsequent implications for determination of the risk of recurrence.
Abnormalities, Drug-Induced↗
Prenatal sonographic diagnosis of Jeune syndrome.
Asphyxiating thoracic dysplasia (Jeune syndrome) is characterized by a narrow thoracic cage, which causes severe respiratory failure with frequent perinatal death; brachymelia, predominantly of the rhizomelic type; renal anomalies; and characteristic radiographic findings of ribs, pelvis, and long tubular bones. Inheritance is autosomal recessive. Prenatal sonographic examination was performed at 17 and 19 weeks of a fetus of parents whose first child had died of Jeune syndrome. The length of the humeri, femora, and tibiae was short (below the mean) for gestational age, and the thorax was abnormally flat and narrow. The iliac wings were square-shaped. We concluded that the fetus had Jeune syndrome. The characteristic skeletal changes of Jeune syndrome are distinct enough at 17 weeks of fetal age to permit sonographic diagnosis.
Adult↗
The fragile X syndrome (Martin-Bell syndrome). Clinical and cytogenetic findings in 16 prepubertal boys and in 4 of their 5 families.
Clinical and cytogenetic findings from 16 prepubertal males with the fragile X syndrome (X-linked mental retardation with postpubertal macro-orchidism and fragile site at Xq27/8, or Martin-Bell syndrome) and from their families are reported. During the first postnatal years, protruding, large ears, full periorbital tissue, and thick septum and alae nasi were the most characteristic phenotypic findings, while after approximately 6 years of age a longish face with full lips and prominent maxilla and mandible became more distinct. It was estimated that a clinical suspicion of the fragile X syndrome could be made in most of the 16 boys from phenotypic findings in combination with the characteristic developmental profile described in our previous paper. The marker X chromosome was demonstrated in each of the 16 patients; the incidence of fra(X)-positive cells did not correlate with either age or the degree of mental retardation. 13 boys stemmed from 2 families, the other 3 were sporadic cases. In one family with 11 affected boys, the gene was transmitted by 4 brothers, grandfathers to the probands, who were intellectually normal; three of them did not show the clinical picture of the fragile X syndrome and did not express the marker. All mentally subnormal heterozygote females and one half of daughters of heterozygotes revealed the marker, but this was present only in a minority of non-retarded adult heterozygotes. In contrast to the overall incidence of about 1/4 to 1/3 mentally retarded heterozygotes, all 15 daughters of the four normal obligatory hemizygous brothers were of normal intelligence.
Child↗
Endogenous blockage and delay of the chromosome cycle despite normal recruitment and growth phase explain poor proliferation and frequent edomitosis in Fanconi anemia cells.
BrdU-Hoechst flow cytometry was employed to study the proliferation kinetics of blood lymphocytes from patients with Fanconi anemia (FA). Compared to controls, untreated FA lymphocytes show normal response to PHA stimulation, normal G0/G1 exit rates, and normal first S-phase durations. The G2 phase of the first cell cycle, however, is severely prolonged, and 24% of the recruited population become arrested during the first chromosome cycle (S, G2/M phases). The delay suffered during G2 appears to be compensated in part by a subsequent G1 phase duration that is unusually short for postnatal human cells (3.7 +/- 0.5 hrs). In analogy to what has been observed in other cell systems after experimental delays of the chromosome cycle, we therefore postulate that at least some FA cells enter their second growth phase without prior completion of the delayed chromosome cycle. Renewed replication would ensue in such cells without prior passing through mitosis and cytokinesis, leading to endoreduplication, which is a frequent finding in the FA syndrome.
Adolescent↗
Cyclopia and cebocephaly in two newborn infants with unbalanced segregation of a familial translocation rcp (1;7)(q32;q34).
This is a report of a family with a balanced reciprocal translocation, rcp (1;7)(q32;q34). Among pregnancies from translocation carriers, there were several miscarriages, and two unbalanced offspring with dup(1q32----qter) and del (7q34----qter) who died perinatally. One was a male cyclops with additional brain malformations and hydronephrosis, the other was a cebocephalic female with multiple additional malformations of heart, kidneys, and skeleton. In both pregnancies, the brain and renal anomalies were detected prenatally by ultrasound, in the cyclops during the 32nd and in the cebocephalic fetus during the 28th week of gestation.
Abnormalities, Multiple↗
Optiz trigonocephaly syndrome: report of two cases.
We report two patients with Opitz trigonocephaly syndrome. Both children showed the pattern of abnormal findings characteristic of this syndrome, including trigonocephaly, upslanted palpebral fissures, inner epicanthic folds, broad alveolar ridges, small chin, short neck with loose skin, muscular hypotonia and cardiac defect. An 8-week-old girl had multiple gingival frenula, brachydactyly, syndactyly of toes and anal stenosis in addition, while a boy who died at 28 h from cardiac failure showed multiple joint contractures, cryptorchidism and renal cortical cysts.
Abnormalities, Multiple↗
Prenatal ultrasonographic diagnosis of holoprosencephaly. Two cases of cebocephaly and two of cyclopia.
Four instances of ultrasonographic detection of holoprosencephaly, one during the second and three during the third trimester of gestation, are reported. Horizontal scans of the skull showed absence of midline structures, communication between the lateral ventricles and reduction of the brain mass, particularly anteriorly. Sagittal scans revealed absence of the nose and presence of a proboscis in the fetuses with cyclopia and hypoplasia of the nose in one cebocephalic fetus. Hypotelorism or a single midline orbit are further pathognomonic features detectable by ultrasound, but only the latter was identified in one of the cyclopic fetuses. Facultative findings of holoprosencephaly identifiable by ultrasound, but absent in our cases, are premaxillary agenesis and bilateral cleft lip and maxilla. The characteristic pattern of ultrasonographic findings in holoprosencephaly should allow an unequivocal prenatal diagnosis during the second and third trimester.
Adult↗
Familial incidence of congenital anorectal anomalies.
We describe two families with pedigrees over three and two generations with nine members affected with anorectal malformations. Both pedigrees are compatible with autosomal dominant inheritance with variable penetrance and expression or with multifactorial inheritance with a high genetic load. The recurrence risk is thought to be in the range of 10% to 20% for first degree relatives of affected members.
Adolescent↗
Trisomy 9 (pter----q1 to q3): the phenotype as an objective aid to karyotypic interpretation.
The phenotypic findings of three patients whose karyotypic interpretations were uncertain were compared to patients with trisomy 9 (pter---q1 to q3). One with an extra, small acrocentric chromosome and another with a trisomy due to an inherited C/G translocation have a phenotype compatible with the trisomy 9 (pter----q1) syndrome. In a third patient reported with 47,XY,?16+, the trisomy 9p probably extends past the q1 region.
Abnormalities, Multiple↗
Antley-Bixler syndrome in sisters: a term newborn and a prenatally diagnosed fetus.
Sisters with the Antley-Bixler syndrome are reported herein. The first infant died at 14 days of respiratory failure and the following findings characteristic of the syndrome: craniosynostosis of coronal and lambdoid sutures, brachycephaly, frontal bossing, severe midface hypoplasia with proptosis and choanal stenosis/atresia, humero-radial synostosis, medial bowing of ulnae, long slender fingers with camptodactyly, narrow iliac wings, anterior bowing of femora, cardiac and renal malformations. Unlike two previously published cases, she did not have connatal fractures, but she had vaginal atresia. Ultrasound examination in a subsequent pregnancy showed immobility at the elbows of the fetus, humero-radial synostosis, medial bowing of ulnae, and long hands and fingers. The fetus also had mild bowing of femora. The pregnancy was terminated in the 21st week and the findings were confirmed by clinical and radiologic examinations. Additional autopsy findings included cardiac and renal malformations. The Antley-Bixler syndrome is a recognizable malformation syndrome with a probable autosomal recessive mode of inheritance, which can be diagnosed in the fetus by midtrimester ultrasound examination.
Abnormalities, Multiple↗
The campomelic syndrome: review, report of 17 cases, and follow-up on the currently 17-year-old boy first reported by Maroteaux et al in 1971.
We report 17 cases of the campomelic syndrome (CS) and a follow-up of one of the original patients of Maroteaux et al who is now 17 years old. Our review is based on 97 patients, including our own. An infant with the CS presents at birth with spectacularly short and bowed femora and tibiae. The initial chest radiograph confirms the diagnosis by demonstrating extremely small bladeless scapulae and hypoplastic pedicles of many thoracic vertebrae. Ossification of the sternal segments, pubis, talus, and knee epiphyses is also retarded. Usually the hips are dislocated and talipes equinovarus deformities are present. There is a small chondrocranium and a disproportionately large neurocranium. The bell-shaped chest, narrow superiorly, does not explain the degree of respiratory distress that soon ensues. Narrow airways from defective tracheo-bronchial cartilage can often be demonstrated on the radiograph, but micrognathia, retroglossia, cleft palate, hypoplastic lungs, and even CNS-based hypotonia contribute to the respiratory problem. Internal anomalies include frequent absence of olfactory bulbs and tracts and dilatation of cerebral ventricles, heart defects (PDA, VSD, stenosis of aortic isthmus), hydroureter and hydronephrosis, renal hypoplasia, renal hypoplasia, and rarely renal cysts.
Abnormalities, Multiple↗
Part II. Amyoplasia: twinning in amyoplasia--a specific type of arthrogryposis with an apparent excess of discordantly affected identical twins.
We report on 11 cases of amyoplasia in one of identical twins. In total, 135 patients with amyoplasia were ascertained from a study of 350 patients with multiple congenital joint contractures (arthrogryposis). These 11 cases of identical twins with amyoplasia represent 8% of our patients with amyoplasia. At least 18 sets of twins with congenital contractures have been reported previously. However, only four of these appear to involve identical twins discordant for amyoplasia. Thus, 15 cases in which only one of identical twins are affected with amyoplasia have been identified.
Adolescent↗
Ring chromosome 21 in phenotypically apparently normal persons: report of two families from Switzerland and Italy.
If a ring 21, originating from breaks close to the telomere of 21q and anywhere in 21p, replaces a normal 21, it may be associated with an apparently normal phenotype. An apparently normal mother and son were ascertained by a prenatal chromosome study. A second mother, with a ring 21 but without gross anomalies, is short of stature, has epilepsy and has a low normal intelligence. He daughter is a mosaic: 46,XX/47,XX,+r(21) and has the Down's syndrome. None of these four persons was found to have mitoses with more than one ring 21 or with rings of double size.
Adult↗
46,XX/46,XY chimerism in a phenotypically normal man.
Some twenty cases of dispermic chimeras with the karyotype 46,XX/46,XY, discovered because of gonadal dysplasias or a true hermaphroditism, have been reported. This is a report of a phenotypically normal man with 46,XX/46,XY chimerism in whom a prepubertal finding of positive X-chromatin was interpreted as Klinefelter syndrome. The diagnosis was revised 11 years later when the family doctor, who doubted the earlier diagnosis because of the patient's normal-sized testes, sent him to an outpatient clinic. The young man was 23 years old, athletic (74kg, 180cm), with normal body proportions, normal sexual hair distribution, normal libido and potency, normal endocrine parameters, and a normal spermiogram. The karyotype revealed an XX/XY mosaic in a proportion of 1:2. An identical set of maternal markers (Q- and C-banding) was present in male and female cells. Differences were found with respect to two paternal markers. Furthermore, blood, serum, and red cell enzyme groups in five systems showed two phenotypes, again with duality of paternal origin. It is concluded that a positive X-chromatin in prepuperty, especially in the absence of supporting clinical features, must be followed by a karyotype study.
Adult↗
Deficiency, transposition, and duplication of one 15q region may be alternatively associated with Prader-Willi (or a similar) syndrome. Analysis of seven cases after varying ascertainment.
Seven patients are described who have some or all of the symptoms of Prader-Willi syndrome. They were ascertained by varying criteria starting either from the clinical picture or from the identification of a chromosome abnormality involving the proximal portion of the long arm of chromosome 15. The chromosome abnormalities consisted of two balanced translocations (15;18 and 8;15), three unbalanced ones (15;18, 15;19, and 9;15), and one interstitial deletion of bands 15q11 and q12. The seventh case had an unidentified extra chromosome. These data and a review of the literature led to the conclusion that deficiency, transposition, and even duplication of the region(s) 15q11-q13 may all result in a syndrome which is identifiable with or similar to the Prader-Willi syndrome.
Adolescent↗