Jarcho–Levin Syndrome Associated with a Complex Congenital Heart Anomaly

Jarcho-Levin syndrome is characterized by "crab-like" rib cage deformity and multiple vertebral anomalies that cause respiratory failure. Reports of complex congenital heart defects with this syndrome are rare. We describe a female infant with this syndrome and a complex congenital heart defect and review the literature. Congenital heart defects are occasionally complicated by Jarcho-Levin syndrome. Heart defects involving heterotaxic morphology should be included as one of the important clinical features of this syndrome.     

Segmental costovertebral malformations: association with neural tube defects. Report of 3 cases and review of the literature.

Patients with spondylocostal dysostosis (SCD) have vertebral abnormalities and numerical or structural rib anomalies that produce thoracic asymmetry. Rib anomalies and dysmorphism are the typical features that differentiate this syndrome from spondylothoracic dysostosis (STD). Jarcho-Levin syndrome is a severe form with involvement of the whole vertebral column. Other associated findings such as congenital heart defects, abdominal wall malformations, genitourinary malformations and upper limb anomalies may be found; in addition, neural tube defects (NTDs) have been associated with this malformation. SCD is transmitted both in a recessive form and as a dominant defect. We report on 3 children with SCD; 2 also had NTDs. All of them were studied with X-rays and spinal magnetic resonance (MR), and over the same period they underwent multidisciplinary clinical functional evaluation. One of our cases with NTD also presented polythelia, which has not previously been described in patients with SCD. The common association of segmental costovertebral malformations with NTDs could be related to an early gastrulation genomic defect, or one after gastrulation, when there are two independent somitic columns. The latter sometimes progresses and then involves primary and secondary neurulation. Also, the association of SCD with NTDs could be related to the interaction of different genes, resulting in this complex phenotype. Therefore, additional genetical and embryological studies are necessary to provide evidence of an etiological link between SCD and NTD.     

Genetics of congenital cardiopathies

Congenital heart malformations are the most common of all birth defects, affecting 0.5-1% of all live births. Some of these malformations are due to genetic anomalies. Patterns of autosomal dominant, autosomal recessive and X-linked inheritance have been described. Mitochondrial inheritance and chromosomal anomalies can also be responsible for congenital heart malformations. Several genes for congenital heart defects have been identified. We review current knowledge on the genetic etiology of congenital heart disease.     

CONGENITAL HEART DISEASE AND ITS ASSOCIATION WITH OTHER CONGENITAL MALFORMATIONS FOUND AT AUTOPSY

The objective was to determine if a study of other malformations found at autopsy in patients with congenital heart disease would contribute to an understanding of the mechanisms involved in the formation of these anomalies. In a large general hospital autopsies in children with congenital heart disease were selected, and the different cardiopathies were divided into 3 groups: those with isolated heart lesions, those with single gene mutants, as well as chromosome malformations, and those with idiopathic malformations not associated with a genetic syndrome. Because the cardiopathies most often associated with genetic syndromes were the septal defects in general (p = .001), it was presumed that these are influenced to a considerable extent by genetic factors. The association of left heart hypoplasia and coarctation of the aorta with multiple idiopathic malformations, particularly in the lower half of the body (p = .002), suggests that the latter may be due to vascular disruptions, because of the interruption of the flow of oxygenated blood in the embryo-fetus produced by these heart defects. Cranial defects were not associated with left heart obstruction, and are therefore unlikely to be produced by vascular disruption.     

Spondylothoracic dysplasia with diaphragmatic defect: a case report with literature review.

Spondylothoracic dysplasia (Jarcho-Levin syndrome) is a syndrome of unknown etiology. We describe a new case with diaphragmatic eventration. Literature review for cases of Jarcho-Levin syndrome with diaphragmatic defects, which were six cases, revealed that renal affection increased when diaphragmatic defects associate the syndrome with pulmonary hypoplasia. Thus, the subgroup of spondylothoracic dysplasia with diaphragmatic defect is a more severe subgroup of the syndrome rather than the other forms of this syndrome. Relating the described anomalies in this case and that of the literature cases to the known embryological basis may point to a pivotal developmental link between lung, kidney and diaphragm, possibly the posterior mesenchyme.     

EXTRASKELETICAL MALFORMATIONS IN THE JARCHO-LEVIN SYNDROME: POSTMORTEM STUDY OF THREE CASES

We report on pathologic examination of three autopsied newborns with Jarcho-Levin syndrome. The most important abnormalities noted were multiple extraskeletical defects such as cardiovascular, urogenital, respiratory, and central nervous system malformations. These cases add new information to the multiple vertebral segmentation defects found in this syndrome.     

Symptomatic moyamoya disease and aortic coarctation in a patient with Noonan's syndrome: strategies for management.

Noonan's syndrome is a multiple congenital anomaly syndrome with characteristic facial features, short stature, congenital heart defects and a recently reported association with moyamoya disease. We report a case of symptomatic moyamoya disease and aortic coarctation in a patient with Noonan's syndrome. The case illustrates the need for a rational, coordinated treatment plan for dealing with the cardiac and neurologic syndromic anomalies to help avoid undesirable outcomes.     

Unusual hand malformations with cardiac defects—A variant of heart-hand syndrome IV

Reported below is the association of unusual hand malformations and congenital cardiac anomalies, possibly a variant of Heart-Hand syndrome IV in a 10 year old male. In addition to these malformations, he also had genitourinary defects. The differential diagnosis of polydactyly with cardiac defects is discussed along with a review of relevant literature.     

Congenital malformations at birth among liveborn infants in Afghanistan,a prospective study

In a prospective study of 5,276 consecutive liveborn babies, 291 (5.5%) infants were diagnosed to have 473 congenital malformations. The incidence of major and minor malformations was 2.4 per cent and 3.1 percent respectively. Musculoskeletal defects accounted for 41.7 per cent of major anomalies. Among individual anomalies, congenital dislocation of hips, cleft lip±palate, microcephaly, club feet, polydactyly, hypospadias, Down syndrome and asymmetric crying facies had a frequency greater than 1 per 1000 livebirths. The incidence of neural tube defects was 3 per 1000 total births. The history of parental consanguinity was significantly higher among parents of infants with major congenital malformations as compared to unaffected control infants.     

Spectrum of congenital malformations in the newborn

Of 6,274 consecutive live-births during 1975–78, 170 (2.7 percent) infants were diagnosed to have 241 major congenital malformations. The incidence of malformations among preterm was almost twice (5.3 per cent), while two-thirds of infants with internal malformations weighed less than 50th centile for their gestational age at birth. Musculoskeletal defects accounted for one-third of all malformations. Out of systemic defects, central nervous system anomalies were most frequent (12.9 per cent) while other system defects (except respiratory system) had an identical frequency of about 10 per cent. The incidence of neural tube defects was found to be 7 per 1000 total births. Among individual anomalies, club foot, spina bifida, polydactyly, left-to-right cardiac shunt, clef lip ±cleft plate, hydrocele, Down syndrome and congenital dislocation of hips had a frequency greater than 1 per 1000 live-births.     

Congenital Cardiac Defects: A Possible Association of Aminopterin Syndrome and In Utero Methotrexate Exposure?

Folate antagonist are chemotherapeutic agents used in many neoplastic, autoimmune, and inflammatory disorders. The first suggestions that folic acid antagonists were teratogenic in humans were based on reports of failed terminations in mothers given aminopterin in the first trimester. Newborns who survived after aminopterin exposure were noted for years to have defects of the neural tube, skull, or limbs. There is now a well-defined syndrome of congenital anomalies associated with the use of aminopterin. The aminopterin syndrome consists of cranial dysostosis, hypertelorism, anomalies of the external ears, micrognathia, limb anomalies, and cleft palate. The use of aminopterin has now fallen out of favor. Methotrexate is a folate antagonist that is now used more frequently. A similar pattern of malformations has been found in fetuses exposed to methotrexate. If used during pregnancy, it can cause congenital malformations or fetal death. A consistent association between methotrexate exposure and cardiac, renal, or gastrointestinal malformations has not been reported. We report two patients who presented with classic features of aminopterin syndrome combined with significant congenital cardiac malformations after first-trimester in utero methotrexate exposure. Both of these patients survived to undergo corrective cardiac surgery.     

Fryns Syndrome: A New Definition

Fryns syndrome is a lethal, autosomal recessive syndrome of multiple congenital anomalies described by Fitch et al. in 1978 and Fryns et al. in 1979. As originally described, the major diagnostic criteria included abnormal facies; small thorax with widely spaced, hypoplastic nipples; distal limb and nail hypoplasia; and diaphragmatic hernia with pulmonary hypoplasia. Malformations involving other systems occurred irregularly in published reports. We reviewed 41 published cases of Fryns syndrome and added 4 cases of our own. The major diagnostic criteria described by Fryns were consistent in all cases with the exception of two criteria. Narrow thorax with hypoplastic nipples and gastrointestinal anomalies were present in less than 50% of the cases. Although for 16 of the 41 published cases there was no information on central nervous system findings, 21 of the 29 remaining cases (72%) had CNS malformations. These lesions were absence of corpus callosum, arhinencephaly, and heterotopia of cerebral and cerebellar tissue. Similarly, for 12 of the 41 published cases there was no information on cardiovascular findings but 29 of the 33 remaining cases (88%) had congenital heart disease. These lesions were ventricular septal defects, atrial septal defects, and persistent left superior vena cava. We conclude that central nervous system anomalies and congenital heart disease should be added to the major diagnostic criteria of Fryns syndrome.     

Sacral meningocele with conotruncal heart defects: a possible autosomal recessive trait

Three of four siblings had sacral meningocele with subsequent development of hydrocephaly; two died during the neonatal period due to conotruncal heart defects (transposition of the great vessels and truncus arteriosus type I, respectively). An in utero diagnosis of open neural tube defect was made on the third sibling; persistent slightly elevated alpha-fetoprotein levels in amniotic fluid and increased number of rapidly adhering cells in short term amniotic cell culture were found. The unique combination of sacral meningocele and conotruncal malformations in this sibship suggests a new autosomal recessive condition. It also emphasizes the heterogeneity of both the open neural tube defects and congenital heart defects. Awareness of this variant is necessary in regard to the 25% recurrence risk instead of the 3% to 5% recurrence risk given for both congenital heart defects and open neural tube defects as isolated anomalies. The difficult prenatal diagnosis for the small neural tube defect should be appreciated.     

A CASE OF JARCHO-LEVIN SYNDROME ASSOCIATED WITH BILATERAL CYSTIC RENAL DISEASE AND WILMS TUMOR: MR Imaging Findings

Jarcho-Levin syndrome (JLS) is a congenital disorder characterized by a variety of vertebral and costal anomalies that result in thoracic deformity. Hitherto, a plethora of associated anomalies have been described in several reports. In this report, the authors describe a case of JLS who has Wilms tumor and bilateral cystic renal disease. To the authors’ knowledge, there is only a single case of JLS who presented with multiple renal cortical cysts, but none with an associated Wilms tumor in the literature. Additional anomalies seen in the present case that are related with this syndrome are also discussed.     

Spectrum of congenital heart defects in Croatia

The aim of our study was to investigate the incidence of congenital defects in children born in Croatia during a period of 5 years, its association with extracardiac malformations, its treatment, and outcome. Medical information about the patients was obtained from 14 paediatric cardiology centres that cover the whole country. Diagnosis was made by clinical findings, electrocardiography, chest X-ray, echocardiography, catheterisation, or autopsy. Between October 1, 2002 and October 1, 2007, there were 205,051 live births in Croatia, 1,480 of which were patients diagnosed with congenital heart disease, accounting for 0.72% of the live-born children. The distribution was made up of 34.6% children with ventricular septal defect, 15.9% with atrial septal defect, 9.8% with patency of arterial duct, 4.9% with pulmonary valvar stenosis, 3.3% with tetralogy of Fallot, 3.3% with transposed great arteries, 3.3% with aortic stenosis, 3.2% with aortic coarctation, 4.3% with atrioventricular septal defect and common atrioventricular orifice, 2.3% with hypoplastic left heart syndrome, and 8.3% other with severe defects. The average age in the time of diagnoses is 70.41 days (SD, 188.13), with low average time of diagnoses of severe heart defects, 9.6 days (SD, 32.52). Among patients, 14.5% had chromosomal defects, syndromes, and/or other congenital major anomalies. During the study, 57 patients died because of cardiac anomalies or other related problems, 24 who died were operated. The rates of specific cardiac defects and association with extracardiac malformations are generally comparable with those reported in similar studies. In spite of all problems, mortality rate of 3.85% is low but could be improved.     

A case with proximal femoral focal deficiency (PFFD) and fibular A/hypoplasia (FA/H) associated with urogenital anomalies

Malformations of the lower limbs are rare and heterogeneous anomalies. Some congenital anomalies involving face, gastrointestinal system, skeletal system, urogenital system, heart, lung and diaphragma associated with lower limb malformations have been described in the literature. Here, we report a case of left proximal femoral focal deficiency (PFFD) together with fibular aplasia associated with left undescended testis and hypospadias. The putative embryologic mechanisms of lower limb defects and their possible association with lower urogenital tract malformations are also discussed.     

Fetal alcohol syndrome in developmental age. Neuropsychiatric aspects

Alcohol constitutes one of the main risk factors for the health of the newborn infant and is also one of the leading causes of cognitive deficit. The distinctive pattern of abnormalities that characterizes fetal alcohol syndrome (FAS) includes: pre- and postnatal growth retardation, cognitive deficit, behavior and language disorders, cerebral malformations (schizencephaly, polymicrogyria, agenesis of the corpus callosum), facial changes (short palpebral fissures, low nasal bridge, anomalies of the auricle, maxillary hypoplasia, cleft lip and palate) and organ anomalies (heart defects, renal and skeletal malformations). As occurs with any teratogenic agent, the variability of phenotypic expression is wide and depends on dose, gestational stage, duration of exposure, maternal and fetal metabolism and other environmental and genetic factors. This study describes 6 subjects with FAS who express various characteristics of the clinical spectrum of the syndrome.     

Socioeconomic inequalities in risk of congenital anomaly.

AIMS: To investigate socioeconomic inequalities in the risk of congenital anomalies, focusing on risk of specific anomaly subgroups. METHODS: A total of 858 cases of congenital anomaly and 1764 non-malformed control births were collected between 1986 and 1993 from four UK congenital malformation registers, for the purposes of a European multicentre case control study on congenital anomaly risk near hazardous waste landfill sites. As a measure of socioeconomic status, cases and controls were given a value for the area level Carstairs deprivation index, by linking the postcode of residence at birth to census enumeration districts (areas of approximately 150 households). RESULTS: Risk of non-chromosomal anomalies increased with increasing socioeconomic deprivation. The risk in the most deprived quintile of the deprivation index was 40% higher than in the most affluent quintile. Some malformation subgroups also showed increasing risk with increasing deprivation: all cardiac defects, malformations of the cardiac septa, malformations of the digestive system, and multiple malformations. No evidence for socioeconomic variation was found for other non-chromosomal malformation groups, including neural tube defects and oral clefts. A decreasing risk with increasing deprivation found for all chromosomal malformations and Down's syndrome in unadjusted analyses, occurred mainly as a result of differences in the maternal age distribution between social classes. CONCLUSION: Our data, although based on limited numbers of cases and geographical coverage, suggest that more deprived populations have a higher risk of congenital anomalies of non-chromosomal origin and some specific anomalies. Larger studies are needed to confirm these findings and to explore their aetiological implications.     

7p-deletion syndrome

A similar pattern of dysmorphic features and congenital malformations was found in two infants, one with a larger terminal deletion of 7p13-pter and the other with a smaller interstitial deletion of 7p13-p15. The more prominent features of the syndrome include plagioturricephaly (which is caused by premature asymmetric closure of the frontal and coronal sutures), osseous defects of the parietal bones, short fingers, proximally implanted thumbs (in both), microphthalmia, congenital heart defect, and hydronephrosis (one). In addition, both patients revealed intrauterine and postnatal growth retardation and pronounced mental deficits.     

Double Aortic Arch: An Unreported Anomaly with Kabuki Syndrome

Kabuki syndrome is a rare congenital disorder characterized by mental retardation, postnatal dwarfism, visceral anomalies, and peculiar facies (resembling the makeup of actors in Kabuki, traditional Japanese theater) initially described in Japan. Congenital heart and great vessel defects are the most frequent visceral anomalies found in children with Kabuki syndrome. Although many cardiovascular defects have been described, a double aortic arch has never been reported with Kabuki syndrome.