The fetal phenotype of the 18p-syndrome. Report of a male fetus at twenty-one weeks

Morphological and cytogenetic findings in a male fetus at 21 weeks gestation after prenatally detected monosomy 18p are reported. The fetus displayed dysmorphic features resembling the 18p-syndrome, such as decreased head circumference, slightly receding forehead, hypertelorism, epicanthus, horizontal palpebral fissures, depressed nasal bridge, long philtrum, carp mouth, irregular crenated maxillar alveolar ridge, retrognathia, lowset dysplastic ears with posterior rotation, edema of neck, hands and feet respectively, fingers with drop-shaped tips, short first toes with dysplastic nails, hypoplastic male external genitalia. After termination of the pregnancy, biopsies from different fetal organs as well as from the placenta were taken and set up for long term cell cultures. The metaphases of fetal organs all showed the karyotype 46,XY,18p-. A fetal blood culture failed to grow. Unexpectedly, the metaphases of the placenta showed the mosaic karyotype 46,XY/46,XY,18p-/46,XY,18p+.     

A case of congenital warfarin syndrome due to maternal drug administration during the pregnancy

Warfarin, which is used for anticoagulant therapy, rarely produces congenital warfarin syndrome characterized with hypoplastic nose, stippled epiphyses, and skeletal abnormalities when ingested during pregnancy. Here, we present a male infant, whose mother was treated with warfarin because of a prosthetic heart valve replacement after rheumatic heart disease, with signs of warfarin embryopathy. The mother's first pregnancy at 12 weeks gestation resulted in abortus due to warfarin toxicity. Subsequently, she delivered two healthy girls after her treatment had changed to low molecular heparin during pregnancy periods. We want to emphasize that risk-benefit ratio should be well weighed by both obstetricians and cardiologists when considering warfarin therapy for a woman at childbearing age.     

Clinical findings in an Arab boy with ring (14)(mos 46,XY,r(14)/45,XY,-14)

A five-month male Arab child with clinical features of ring(14) is reported. He had recurrent seizures and chest infections, microcephaly, elongated face, short palpebral fissures, broad nasal bridge, long philtrum, fish-like mouth with thin lips, micrognathia, low-set ears and retinal pigmentation with yellow-white spots on the maculae. In addition brachydactyly of fingers and toes, hypoplastic scrotum and mental deterioration were present.     

Full trisomy 22 in a newborn infant

Karyotype 47,XY,+22 was found in a newborn infant with primitive and low-set ears, bilateral preauricular pit, broad nasal bridge, antimongoloid palpebral fissures, macroglossia, enlarged sublingual glands, cleft palate, micrognathia, clinodactyly of the fifth fingers, hypoplastic finger nails, hypoplastic genitalia, short lower limbs, bilateral sandal gap and deep plantar furrows. The child developed signs of congenital heart disease and died at the age of 10 weeks. Non-disjunction studies showed maternal origin (meiosis I) of the extrachromosome.     

An analphoid marker chromosome inv dup(15)(q26.1qter), detected during prenatal diagnosis and characterized via chromosome microdissection

A small, mosaic, C-band negative marker chromosome was detected in amniocyte cultures during prenatal diagnosis due to advanced maternal age. Following spontaneous premature labor at 29 weeks gestation, a dysmorphic infant was delivered, with flat nasal bridge, short palpebral fissures, micrognathia, high forehead, low-set ears, telecanthus and corneal dystrophy. Additional folds of skin were present behind the neck, and feet, fingers and toes were abnormally long. The child died at age five days, after two days of renal failure. The origin of the marker chromosome was subsequently identified from a cord blood sample, via chromosome microdissection. Through reverse FISH, we found the marker to be an inverted duplication of the region 15q26.1-->qter. FISH with alphoid satellite probe was negative, while whole chromosome 15 paint was positive. Both ends of the marker chromosome were positive for the telomeric TTAGGG probe. These data, plus the G-banding pattern, identified the marker as an analphoid, inverted duplicated chromosome, lacking any conventional centromere. We discuss the etiology and clinical effects of this marker chromosome, comparing it to the few reported cases of "tetrasomy 15q" syndrome. We also discuss the possible mechanisms that are likely responsible for this neocentromere formation.     

A family study of dermatoglyphic traits in India. Resolution of genetic and environmental effects for manus,pes and total pattern ridge counts in man

Various constructed ridge count phenotypes were studied in two endogamous populations from peninsular India. Heritabilities were estimated for five summed pattern ridge count traits: fingers and toes together; palms and soles together; fingers and palms together (manus); toes and soles together (pes); and fingers, palms, toes and soles together, defined as the total ridge count in man. In general, these phenotypes were found to he highly heritable, with the summed ridge counts for fingers and toes, and total ridge count showing almost Complete determination by additive polygenes. Total manus and pes pattern counts are less heritable. Little or no uterine environmental effects were detected for any of these phenotypes.     

Relative lengths of fingers and toes in human males and females

Digital scans of the hands and feet were obtained from 62 heterosexual females and 60 heterosexual males. Scans only of the hands were obtained from 29 homosexual females and 35 homosexual males. The lengths of the individual fingers and toes were estimated from those images by two experienced judges, and length ratios were constructed for all possible pairs of fingers (or toes) on each hand (or foot). Thumbs were not measured, but the great toe was measured and used to construct length ratios. Past research had concentrated on the relative lengths of the index and ring fingers (the 2D:4D ratio). This ratio is close to 1.0 in females and smaller than 1.0 in males. Here 2D:4D did exhibit the largest sex difference, for both hands, followed by 2D:5D and 3D:4D. The sex differences were larger for the right hand than for the left. For both homosexual females and homosexual males, nearly all of the length ratios for fingers were intermediate to those for heterosexual females and heterosexual males; that is, the ratios of homosexual females were masculinized and those of homosexual males were hypomasculinized, but few of these differences were significant. Because many toes were substantially arched, acceptable estimates of length often could not be obtained from the two-dimensional scans, meaning that conclusions about toes are much less certain than those for fingers. Nevertheless, the length ratios were generally larger for toes than for fingers, and the sex differences were generally smaller for toes.     

Tetrasomy of the short arm of human chromosome 18: cytogenetics and phenotypic disorders

Two mentally retarded girls with a small metacentric nonsatellite extrachromosome were examined. Probands were found to share many clinical features: asthenic constitution, microcephalia, low-set malformed ears, high arched palate, long fingers and toes, a wide gap between first and second toes, clinodactyly of the 1st and 5th fingers, scoliosis. The extrachromosome was unequivocally interpreted as an isochromosome for the short arm of chromosome 18. Review of 12 i (18p) cases permits characterizing a syndrome of tetrasomy 18p.     

THE COEVOLUTION OF HUMAN HANDS AND FEET

Human hands and feet have longer, more robust first digits, and shorter lateral digits compared to African apes. These similarities are often assumed to be independently evolved adaptations for manipulative activities and bipedalism, respectively. However, hands and feet are serially homologous structures that share virtually identical developmental blueprints, raising the possibility that digital proportions coevolved in human hands and feet because of underlying developmental linkages that increase phenotypic covariation between them. Here we show that phenotypic covariation between serially homologous fingers and toes in Homo and Pan is not only higher than expected, it also causes these digits to evolve along highly parallel trajectories under episodes of simulated directional selection, even when selection pressures push their means in divergent directions. Further, our estimates of the selection pressures required to produce human‐like fingers and toes from an African ape‐like ancestor indicate that selection on the toes was substantially stronger, and likely led to parallel phenotypic changes in the hands. Our data support the hypothesis that human hands and feet coevolved, and suggest that the evolution of long robust big toes and short lateral toes for bipedalism led to changes in hominin fingers that may have facilitated the emergence of stone tool technology.     

Aplasia of tibia with split-hand/split-foot deformity. Report of six families with 35 cases and consideration about variability and penetrance

Summary Six families with a total of 34 affected persons with the syndrome of tibial aplasia and ectrodactyly are reported. The spectrum of malformations is compared to that of 99 familial cases from the literature. The full-blown syndrome consists of bilateral aplasia of tibiae and split-hand/split-foot deformity. Additional malformations may be distal hypoplasia or bifurcation of femora, hypo- or aplasia of ulnae, and minor anomalies such as aplasia of patellae, hypoplastic big toes, postaxial and intermediate polydactyly in connection with split-hand deformity, and cup-shaped ears. The mildest visible manifestation may be hypoplastic big toes, the severest is tetramonodactyly or transverse hemimelia. This disorder is autosomal dominantly inherited. The penetrance is markedly reduced.     

A submicroscopic unbalanced subtelomeric translocation t(2p;10q) identified by fluorescence in situ hybridization: fetus with increased nuchal translucency and normal standard karyotype with later growth and developmental delay, rhombencephalosynapsis (RES)

Reaching an accurate diagnosis in children with mental retardation associated or not with dysmorphic signs is important to make precise diagnosis of a syndrome and for genetic counseling. A female case with severe growth and development delay, dysmorphic features and feeding disorder is presented. Antenataly, the fetus was observed to have increased nuchal translucency and a slight hypoplastic cerebellum. A standard karyotype was normal. RES and a submicroscopic unbalanced subtelomeric translocation t(2p; 10q) were demonstrated after birth. We show that within the framework of a collaborative approach, a concerted research of submicroscopic subtelomeric rearrangements should be performed in case of mental retardation associated with facial dysmorphic features, and when other etiologies or non-genetic factors (iatrogenic, toxic, infectious, metabolic...) have been ruled out.     

Trisomy C mosaicism in a seven month old girl

A female infant, first seen at age 7 months and again at 1 3/12 years, exhibited the following physical findings: low birth weight at full term; mental and growth retardation; brachycephaly; micrognathia; high arched palate; low set, slanted malformed pinnae; scant medial eyebrow hair; small, short nose with prominent skin folds over the nasal bridge; short neck; both hands were hypoplastic between thumb and index finger; a tendency to hold thumbs in pronation; abnormal dermatoglyphics; rocker-bottom feet; big toes kept in dorsi-flexed position; mottled skin; hypoplastic clitoris and labia minora.Cytogenetic studies on the patient revealed that 83% of the karyotyped peripheral leucocytes had 46 chromosomes and 17% had 47 chromosomes. Metaphases with 46 chromosomes exhibited the normal female complement. Metaphases with a count of 47 consistently had an extra chromosome in the C group. A labelled metaphase with 47 chromosomes showed only 1 late-replicating chromosome. The sex chromatin count was positive (30%) and no buccal cells with more than one sex chromatin body were observed.This study was supported in part by grants T1-AM-5277 and AM-02504 from the National Institutes of Health, United States Public Health Service.Postdoctoral trainee, National Institute of Arthritis and Metabolic Diseases.     

Acro-coxo-mesomelic dwarfism: a new variety of autosomal recessive dwarfism

Acro-coxo-mesomelic dwarfism seems to be a new autosomal recessive entity, one compatible with survival. This severe, dysmorphic condition is characterized by shortening of median and distal segments of the limbs without anomalies of the spine. Other malformations are clubhand and foot, short malformed fingers, and reduced articular mobility of elbows and hips with radial and femoral dislocations. Skeletal X-rays show the following: delayed bone age; mesomelic shortening of the limbs with cubitus brevus, radius curvus, and mostly fibula agenesis; severe acromelic deformities with clinodactyly of the IIIrd, IVth, and Vth digits and brachyrhizophalangia of the IInd and Vth digits. Brachymetacarpia is diffuse, with a "squashed candle" appearance. The IInd metacarpals and the proximal phalanx of the Vth digits have a peculiar "butterfly wings" appearance. The toes are shortened with a "drumstick" appearance and phalangeal hypoplasia, mostly of the midphalanges; hip dislocation and dysplasia (coxomelic), with hypoplasia of the femoral head and a coxa vara cylindric neck.     

Brachydactylia with symphalangism,probably autosomal recessive

Summary Association, in one patient, of the following malformations: brachydactylia of all segments but terminal phalanges; proximal symphalangism of many fingers and toes; abnormalities of carpal and tarsal bones; partial duplication of both big toes; mild hypertelorism. Genetic transmission seems to be recessive autosomal.     

Distal symphalangism: a report of two families

This study describes distal symphalangism in 36 individuals in two families, one of which is the largest pedigree of this rare defect yet documented. Distal symphalangism is ankylosis or rigidity of the distal interphalangeal joints of the hands and/or feet. The findings of this report substantiate the mutation as an autosomal dominant phenotype. Several manifestations of distal symphalangism were observed, including the lack of cutaneous creases over affected joints, brachydactyly, fourth-finger hypophalangism, absent nails, and rudimentary nails. Variability ranged from just toes affected, to a single finger affected, to all fingers and all lesser toes affected. The most common expression of the mutant gene was rigid index fingers. Craniosynostosis, premature closure of the sutures of the skull, was encountered twice in the larger of the two families. It is a possible pleiotropic effect of distal symphalangism.     

An additional manifestation in acrocallosal syndrome: temporal lobe hypoplasia

Acrocallosal Syndrome is a rare genetic disorder which is characterized by moderate to severe mental retardation, agenesis or hypoplasia of the corpus callosum and polydactyly of fingers and toes. The spectrum of this syndrome is very variable. Prominent forehead, broad nasal bridge, short nose and mandible, hypertelorism, epicanthic folds, large anterior fontanelle and tapered fingers, omphalocele and inguinal hernia are some other common findings in this syndrome. Twenty percent of the patients have associated brain abnormalities such as cerebral atrophy, hypothalamic dysfunction, small cerebrum, micropolygyria, hypoplasia of pons, hypoplasia of cerebellar hemispheres, hypoplasia of medulla oblongata, agenesis or hypoplasia of cerebellar vermis and corpus callosum abnormalities. Here we present a 10-month-old female infant with clinical and radiological findings indicative of acrocallosal syndrome. She was noted to have craniofacial abnormalities suggestive of acrocallosal syndrome, optic atrophy and polydactyly. MRI revealed cerebral atrophy, corpus callosum agenesis, dilated lateral ventricules and unilateral right temporal lobe hypoplasia, the latter not previously reported in the spectrum of this syndrome. Based on this observation we conclude the importance of screening brain abnormalities and present temporal lobe hypoplasia as a new additional anomaly in this syndrome.     

Partial duplication of the long arm of chromosome 5: A case due to balanced paternal translocation and review of the literature

Summary A partial duplication of the distal segment of the long arm of chromosome 5 (q31qter) was observed in an infant with congenital malformations and dysmorphic features. The phenotypically normal father had a balanced translocation between the long arm of chromosome 5 and the short arm of chromosome 9: 46,XY,t(5;9)(q31;p24).The clinical and cytogenetic data obtained from six patients with partial duplications of two different long arm segments of chromosome 5 suggest that partial duplication of the distal long arm of chromosome 5 is associated with microcephaly, hypertelorism, epicanthus, strabismus, large upper lip, low-set, dysplastic ears, in addition to growth and psychomotor retardation. Partial duplication of the proximal part of the long arm of chromosome 5, on the other hand, is associated mainly with musculoskeletal abnormalities including muscle hypotrophy and hypotonia, scoliosis, lordosis, pectus carinatum, cubitus valgus, and genu valgum, in addition to psychomotor retardation. The dysmorphic features in this latter group include a bulging forehead, short nose, thick upper lip, low-set protruding ears and tapering, thin fingers.     

产前超声诊断及漏诊胎儿肢体畸形分析

目的：探讨胎儿肢体畸形超声特征及诊断价值。方法：采用连续顺序追踪法对66342 例妊娠12-40 周孕妇行胎儿四肢畸形筛查。将产前超声诊断结果与引产或产后结果进行对比分析。结果：发生肢体畸形271 例,发生率为0.41 %（271/66342）,包括四肢短小5 例,桡骨发育不全1 例,缺肢畸形5 例,足内翻17 例,手掌畸形3 例,指趾畸形222 例及骨骼多发畸形18 例。其中产前诊断胎儿肢体畸形49 例;漏诊222 例,包括：足内翻3 例、指趾畸形218 例、多发骨骼畸形1 例。胎儿肢体畸形的出现率和产前检出率分别为：四肢短小1.84 %（5/271）、100 %（5/5）;桡骨发育不全0.36 %（1/271）、100 %（1/1）;缺肢畸形1.84 %（5/271）、100 %（5/5）;足内翻6.27 %（17/271）、82.35 %（14/17）;手掌畸形1.10 %（3/271）、100 %（3/3）;指趾畸形81.91 %（222/217）、1. 8%（4/222）;多发骨骼畸形6.64 %（18/271）、94.44 %（17/18）。结论：超声对胎儿手掌、脚掌部位以上畸形的检出率较高。指趾畸形出现率最高,但检出率最低。     

产前超声诊断及漏诊胎儿肢体畸形分析

目的:探讨胎儿肢体畸形超声特征及诊断价值。方法:采用连续顺序追踪法对66342例妊娠12-40周孕妇行胎儿四肢畸形筛查。将产前超声诊断结果与引产或产后结果进行对比分析。结果:发生肢体畸形271例,发生率为0.41%(271/66342),包括四肢短小5例,桡骨发育不全1例,缺肢畸形5例,足内翻17例,手掌畸形3例,指趾畸形222例及骨骼多发畸形18例。其中产前诊断胎儿肢体畸形49例;漏诊222例,包括:足内翻3例、指趾畸形218例、多发骨骼畸形1例。胎儿肢体畸形的出现率和产前检出率分别为:四肢短小1.84%(5/271)、100%(5/5);桡骨发育不全0.36%(1/271)、100%(1/1);缺肢畸形1.84%(5/271)、100%(5/5);足内翻6.27%(17/271)、82.35%(14/17);手掌畸形1.10%(3/271)、100%(3/3);指趾畸形81.91%(222/217)、1.8%(4/222);多发骨骼畸形6.64%(18/271)、94.44%(17/18)。结论:超声对胎儿手掌、脚掌部位以上畸形的检出率较高。指趾畸形出现率最高,但检出率最低。     

Partial trisomy 9q- chromosomal syndrome

Summary The clinical features consisting mainly of enophthalmos, beaked nose, narrow palpebral fissures, receding chin, long fingers and toes, typical for chromosomal syndrome of partial trisomy 9q, were confirmed in a new case.