Musculoskeletal Anomalies Research Articles

混合性難聴を伴ったKlippel-Feil症候群の1例

Klippel-Feil syndrome, which is characterized by the congenital fusion of two or more cervical vertebrae, has a clinical triad consisting of a short neck, decreased cervical mobility and a low posterior hairline. Various musculo-skeletal anomalies and defects of the other organ systems, including hearing loss, have been reported in association with this syndrome. The hearing loss is usually a sensorineural impairment, but can be conductive or mixed deafness in rare instances. A 29 year-old man presented with fusion of several cervical vertebrae, torticollis, scoliosis, platybasia, basilar impression, polydactylia, an undescended testis, a spontaneous pneumorthorax and mixed deafness of the right ear. A tympanotomy revealed a hypoplastic long process of the incus, a defect in the stapes, an abnormal facial nerve and a defect in the oval window.

Variable expression of rib, pectus, and scapular anomalies with Robin‐type cleft palate in a 5‐generation family: A new syndrome?

We report on a 5-generation family with multiple musculoskeletal anomalies, including: Robin-type cleft palate, rib “dysplasia,” scapular hypoplasia, and pectus excavatum. Robin-type clefts are known to be associated with various skeletal malformations; however, most of these include limb anomalies which are not present in this family. To our knowledge, there are no reports of similar conditions in the literature. The transmission through 5 generations and the presence of male-to-male transmission are consistent with autosomal-dominant transmission of a trait with variable expressivity. Am. J. Med. Genet. 73:247–250, 1997. © 1997 Wiley-Liss, Inc.

Variable expression of rib, pectus, and scapular anomalies with Robin-type cleft palate in a 5-generation family: A new syndrome?

We report on a 5-generation family with multiple musculoskeletal anomalies, including: Robin-type cleft palate, rib "dysplasia," scapular hypoplasia, and pectus excavatum. Robin-type clefts are known to be associated with various skeletal malformations; however, most of these include limb anomalies which are not present in this family. To our knowledge, there are no reports of similar conditions in the literature. The transmission through 5 generations and the presence of male-to-male transmission are consistent with autosomal-dominant transmission of a trait with variable expressivity.

Unbalanced t(4;11)(q32;q23) in a 34-year-old man with manifestations of distal monosomy 11q and trisomy 4q syndromes

We present a 34-year-old man with an unbalanced translocation between the long arms of chromosome 4 and chromosome 11. He had manifestations of monosomy 11(q23)--minor facial anomalies, abnormal head shape, cryptorchidism; trisomy 4(q32)--hirsutism, renal disease; and manifestations attributable to both imbalances--heart disease, musculoskeletal anomalies, and mental retardation. FISH studies showed that the chromosome 11q23.3 translocation breakpoint was distal to the rare folate sensitive fragile site (FRA11B). The patient is the oldest reported with both imbalance of 4q+ and 11q-.

Serial examination of 20,248 newborn fetuses and infants: Correlations between drug exposure and major malformations

Maternal medication during the first trimester of pregnancy has been discussed as a risk factor for development of birth defects. The correlation between maternal drug use and major malformations was investigated in a population-based case-control study in Mainz. Over a period of 5 years (1990–1994), 20,248 livebirths, stillbirths, and abortions underwent physical and sonographic examination, and anamnestic data were collected. A total of 1,472 births with congenital anomalies (cases) and 9,682 births without major and minor malformations (controls) were analyzed. We distinguished between 30 different drug categories, which were divided into medication taken continuously (before and during pregnancy; CM) and acute medication (drugs given within the first 3 months of gravidity; AM). Statistically highly-significant results [CM: Odds Ratios (OR) 1.2, Confidence Intervals (CI) 1.1–1.4, P = 0.008; AM: OR 1.2, CI 1.1–1.3, P = 0.008] were established for maternal drug use in correlation to birth defects. For the majority of combinations between drugs and specific malformations no teratogenic risks were found. However, statistically significant associations were recorded for antiallergics and heart anomalies (CM, AM) as well as musculoskeletal anomalies (AM); for bronchodilators and heart anomalies (CM, AM); for antiepileptics and anomalies of the internal urogenital system (CM), as well as cleft palate/cleft lips (AM); for thyroid hormones and anomalies of the nervous system (CM, AM), as well as anomalies of the external urogenital system (CM, AM); for insulin and anomalies of the musculoskeletal system (CM); for digitalis and anomalies of the musculoskeletal system (AM). © 1996 Wiley-Liss, Inc.

Antenatal sonographic diagnosis of clubfoot: A six-year experience

In the period 1988 through 1993, 6351 pregnant women were referred to the Department of Obstetrics and Gynaecology, University "La Sapienza", Roma, for suspected fetal anomalies or maternofetal problems. All underwent serial transabdominal and/or transvaginal ultrasound scanning, which revealed a total of 235 fetuses with hydrocephalus, cardiac, or musculoskeletal malformations. Forty-one clubfeet were detected in 27 pregnancies in the early part of the second trimester of pregnancy. Of these, 14 feet in eight patients were isolated, and were classified as idiopathic. A clubfoot was associated with neural tube defects in six patients, with anomalies of the urinary and/or digestive system in a further six, with a cystic hygroma in two, and with other musculoskeletal abnormalities in the other six patients. Amniocentesis revealed an abnormal karyotype in six fetuses (22.2%). In only two cases was oligohydramnios present. In both these patients, a fetal urinary tract malformation was present Polyhydramnios was found in 18 cases, and a normal amount of amniotic fluid was found in the remaining seven cases. Polyhydramnios was present in six of the eight idiopathic clubfoot fetuses. Clubfoot is associated with musculoskeletal and visceral anomalies in a high proportion of cases. The association of clubfoot with polyhydramnios in a high proportion of cases does not support the hypothesis of intrauterine moulding as an etiological factor in its development. Ultrasonographical prenatal detection of a clubfoot should prompt amniocentesis, as the condition is associated with an abnormal karyotype in a significant proportion of cases.

Routine prenatal ultrasound screening for fetal abnormalities: 22 years' experience.

We describe the results of routine obstetric ultrasound examination over a period of 22 years (1970-91) at the Institut Universitari Dexeus, Barcelona, Spain. A total of 1006 malformed fetuses or neonates were identified at abortion or delivery. The prevalence of fetal abnormalities was 3.03%. Fetal anomalies were diagnosed antenatally in 788 (78.33%) cases. Early prenatal diagnosis (before 22 weeks of gestation) was made in 598 (59.44%) cases. The detection of malformed fetuses increased from 19.75% in the first phase of the study (1970-74) to 96.33% in the last phase (1990-91). The specificity of the method was over 99% throughout the study period. The most frequently diagnosed anomalies were urinary tract anomalies (22.86% of cases), followed by head and neck anomalies (18.68%), musculoskeletal anomalies (8.64%), heart anomalies (7.35%) and gastrointestinal anomalies (7.35%). The earliest diagnosed malformations were those of the thoracoabdominal wall (81.08%), followed by defects of the urinary tract (70.86%) and of the diaphragm (70.83%).

Transvaginal sonographic detection of skeletal anomalies in the first and early second trimesters

AbstractWe report the detection of 42 cases of musculoskeletal anomalies routinely screened by transvaginal sonography at 12‐16 weeks of gestation out of 7325 examined pregnant women (incidence of 0·57 per cent).

Etiology and pathogenesis of heritable connective tissue diseases.

There are many heritable disorders of the connective tissues and many of them produce major musculoskeletal anomalies. The etiology of most of them is unknown, but collagen mutations have been characterized in osteogenesis imperfecta (OI), in some forms of the Ehlers-Danlos syndrome (EDS) and in some of the chondrodysplasias. These diseases, particularly OI, provide a model for investigation of other heritable connective tissue diseases in which the mutant genes have not yet been identified.

Fetal malformations associated with chronic polyhydramnios in singleton pregnancies

Forty-one congenital malformations were found in 28 newborns in a group of 197 cases of chronic polyhydramnios in singleton pregnancies. Of these, a total of 61% ( 17 28 ) was antenatally diagnosed ultrasonically. Nine newborns (4.5%) had malformations of the central nervous system (CNS), 9 (4.5%) cardiovascular malformations, 8 (4.1%) musculoskeletal anomalies, 7 (3.6%) malformations of the urinary and reproductive system, 4 (2%) respiratory system anomalies and 3 (1.6%) anomalies of the gastrointestinal system. Chromosomal abnormalities were found in three cases. As the association of polyhydramnios with fetal congenital anomalies is quite high (14.2% in our series), it is imperative to make a major effort to antenatally detect as many cases as possible. This means that in the case of hydramnios the following are required: ultrasound examination by an expert, echo ultrasonography when no other abnormalities are detected, and maybe even a chromosomal analysis.

Monochorionic diamniotic minimally conjoined twins: A case report

We present the second case of monochorionic diamniotic (MC/DA) conjoined twins. There was minimal conjunction, which was predominantly extrafetal and confined to the periumbilical ventral region. The omphalopagus twins, attached to a single forked umbilical cord, were connected by a shared umbilical hernia containing the ileum of twin B. The only visceral conjunction, located just within the belly of twin A, was midileal with the 2 separate ileums converging toward a short segment of shared muscularis propria and of side-to-side fistulization. Gastrointestinal and musculoskeletal anomalies were present in both twins with severe amyoplasia and arthrogryposis multiplex in twin A. Possible mechanisms underlying this unusual form of MZ twinning are discussed.

Polyhydramnios and associated maternal and fetal complications in singleton pregnancies

During the 10-year period 1 January 1979 to 31 December 1988, polyhydramnios occurred in 537 patients with singleton pregnancies delivered at the Mercy Maternity Hospital. Associated maternal and fetal complications and the perinatal outcome of these pregnancies with polyhydramnios were analysed. In 248 of the 537 pregnancies (46%) in this group there were no maternal complications or fetal malformations and the perinatal mortality (PNM) rate was 2.4%. The PNM rate increased significantly to 13.1% when there was associated pre-eclampsia, 10% with gestational diabetes, and to 7.6% with miscellaneous complications. When polyhydramnios was associated with a fetal or placental malformation the PNM rate was 61.4%. The commonest malformations were central nervous system (31%), musculoskeletal (12%) and gastrointestinal system anomalies (10%). Placental chorioangioma occurred in two patients (0.4%) and both babies died. In women with low oestriol excretion (18% of the 455 tested) the PNM rate increased five times to 22.7%.

Mortality from congenital malformations in England and Wales: variations by mother's country of birth.

Stillbirth and infant mortality from congenital malformations in England and Wales during 1981-5 was investigated according to the mother's country of birth. Significant differences remained after standardising for maternal age and social class. The highest overall mortality was in infants of mothers born in Pakistan (standardised mortality ratio 237), followed by infants of mothers born in India (standardised mortality ratio 134), East Africa (standardised mortality ratio 126), and Bangladesh (standardised mortality ratio 118). Caribbean and West African mothers showed an overall deficit. Mortality was inversely related to social class in all groups except the Afro-Caribbean. Infants of mothers born in Pakistan had the highest mortality in every social class except I, and for most anomalies investigated. Their ratios were particularly high for limb and musculoskeletal anomalies (standardised mortality ratio 362), genitourinary anomalies (standardised mortality ratio 268), and central nervous system anomalies (standardised mortality ratio 239). Our findings highlight the need for further research to identify the causes underlying these differences.

Osteoarthritis Associated with a Ball-and-Socket Ankle Joint

A ball-and-socket joint is an unusual disturbance of normal ankle development. Previous reports have noted good function and the absence of osteoarthritic change in ankles with this configuration. A 50-year-old man with no history of injury developed an osteoarthritic ball-and-socket deformity of the ankle joint. Associated musculoskeletal anomalies included toe syndactylization, genu valgum deformity, and tarsal coalition, a condition that may predispose to the development of this ankle anomaly. Associated valgus deformity of the ankle contributed to the osteoarthritic changes. The conspicuous absence of osteoarthritis in other joints of patients previously reported with this abnormality may be explained by the lack of long-term follow-up examinations.

Health status of young children with cancer following discontinuation of therapy.

This paper reports late effects and health status of 198 children who had cancer or leukemia diagnosed under 2 years of age and their therapies electively withdrawn. This series (92 neuroblastoma [NBL], 57 Wilms' tumor [WT], 46 acute lymphoblastic leukemia [ALL], and 3 non-Hodgkin's lymphoma) was followed for 1-12 years after discontinuation of therapy. Thirty-three children were diagnosed before 1973, 92 between 1973 and 1977, and 73 after 1977 in 16 Italian Pediatric Oncology Centers. As of December 1983, 176 children were reported to be alive and without evidence of primary cancer by physicians responsible for their care. One child died from a second primary tumor, two from late recurrences of the primary cancer, and three from other causes; eight were alive with evidence of primary cancer; and eight were lost to follow-up. Kyphoscoliosis was found in 22 children and other musculoskeletal anomalies in 8. Neurological sequelae were observed in 8 out 35 children with ALL treated with radiotherapy (RT) and intrathecal methotrexate. All but one were in continuous complete remission when they developed seizures (three cases), leukoencephalopathy (three cases), or intracerebral calcifications (two cases). One child had cardiomyopathy and subsequently died from cardiac failure: he had received doxorubicin (400 mg/m2) and mediastinal RT (13 Gy) for NBL. Growth impairments were observed in children with NBL and WT.

Spondylolysis and Pregnancy—A Risk Analysis

A possible interference of various musculo-skeletal anomalies with pregnancy is often discussed by obstetricians. Pregnancy as a risk factor for progression of spondylolisthesis, olisthesis as a risk factor for pregnancy complications, and pregnancy in women with spondylolysis as the cause of increased low-back symptoms, are questions hitherto not analysed. In the present study, a comparison between men, non-pregnant women, and women who had been pregnant, was made with respect to the degree of spondylolisthesis and its subsequent progression over an observation period of at least 20 years. Occurrence and intensity of low-back symptoms, and functional impairment due to low-back symptoms (such as change of work, sick-leave, sick-pension, limitation in non-occupational activities, and treatment) during this long observation time were also analysed. The mean values for the group of women who had been pregnant did not differ from those of the other groups as regards any of these variables. On the basis of these results, it is concluded that pregnancy does not constitute a risk for progression of spondylolisthesis, or for increased low-back symptoms in a woman with spondylolysis. Nor is spondylolysis, with or without olisthesis, a risk factor for pregnancy complications.

Concurrent Agenesis of the Corpus Callosum and Ureteroceles in Siblings

Agenesis of the corpus callosum is an uncommon anomaly that exists in complete and partial forms. It has been associated with other cerebral malformations as well as facial, genitourinary, musculoskeletal, cardiac, and respiratory anomalies.1 Agenesis of the corpus callosum is generally sporadic but it has been reported in several families.2 Ureteroceles frequently occur in association with duplications of the ureters.3 The hereditary occurrence of ureteroceles has been reported in five families.4-8 In this report, we describe two brothers with the simultaneous occurrence of agenesis of the corpus callosum and orthotopic ureteroceles. Two brothers were seen at The Hospital of the Albert Einstein College of Medicine for evaluation of urologic abnormalities.

Congenital spine deformities. A review of 47 cases.

Forty-two cases of congenital scoliosis, four cases of congenital kyphosis and one case of congenital lordosis were reviewed retrospectively from 1975 through 1982, with an average follow-up of 5.09 years. Associated anomalies occurred in 62.5% of the cases, with Sprengel's deformity and Klippel-Feil syndrome being the most common musculoskeletal anomalies. The rate of abnormal intravenous pyelography was 21.8%, and absent kidneys or duplication of collecting systems accounted for the majority of renal abnormalities. Myelographic abnormalities were noted in eight of twenty-five studies and included two cases of diastematomyelia and one tethered cord syndrome. Initial treatment was observation (11), bracing (11), and surgery in the remaining 25 cases. The surgical complication rate was 22.8%. Progressive deformities led to additional surgical procedures in six cases which had previous in situ fusions.

Concurrent Agenesis of the Corpus Callosum and Ureteroceles in Siblings

Agenesis of the corpus callosum is an uncommon anomaly that exists in complete and partial forms. It has been associated with other cerebral malformations as well as facial, genitourinary, musculoskeletal, cardiac, and respiratory anomalies.1 Agenesis of the corpus callosum is generally sporadic but it has been reported in several families.2 Ureteroceles frequently occur in association with duplications of the ureters.3 The hereditary occurrence of ureteroceles has been reported in five families.4-8 In this report, we describe two brothers with the simultaneous occurrence of agenesis of the corpus callosum and orthotopic ureteroceles. Two brothers were seen at The Hospital of the Albert Einstein College of Medicine for evaluation of urologic abnormalities.

Vertebral anomalies and duodenal atresia

Musculo-skeletal anomalies were found in 13infants in a series of 35 with duodenal atresia; an incidence of 37%. In 12 patients the vertebral column was abnormal. This finding equals the high incidence of vertebral anomalies associated with oesophageal and rectal atresia thus suggesting that duodenal atresia could be considered as an integral part of the VATER anomaly. Musculo-skeletal anomalies were found in 13infants in a series of 35 with duodenal atresia; an incidence of 37%. In 12 patients the vertebral column was abnormal. This finding equals the high incidence of vertebral anomalies associated with oesophageal and rectal atresia thus suggesting that duodenal atresia could be considered as an integral part of the VATER anomaly.