Emanuel Syndrome with Unique Cardiac Defects: a Case Series

Emanuel syndrome with unique cardiac defects: a case series

Emanuel syndrome is a rare condition resulting from the presence of an extra chromosome composed of pieces of chromosomes 11 and 22. The clinical presentation varies – the main features of the syndrome include cleft palate, ear anomalies, heart defects, genital anomalies, hypotonia and mental retardation. This report describes two cases of Emanuel syndrome in infants with antenatal diagnoses of congenital heart defects. Extra cardiac features in this case series include microcephaly, hypotonia, cleft palate and necrotising enterocolitis.

Adnan Zafar manuel syndrome is caused by the Other conditions associated with BSc, MBBS, MRCPCH Epresence of an extra chromosome, Emanuel syndrome include cleft palate, Neonatology Registrar which is made up of the top and middle genitourinary tract malformations, James Cook University Hospital, parts of chromosome 22 and the bottom intestinal atresias and craniofacial Middlesbrough part of chromosome 11. The extra dysmorphism. There is significant [email protected] chromosome is inherited from one of the variability in the facial appearance of Milind Chaudari parents. The carrier parent has the usual individuals with Emanuel syndrome. The number of chromosomes however, most common facial features observed MBBS, MD, MRCP Consultant Cardiologist chromosome 11 and 22 have switched include hooded eyelids, deep-set eyes, Freeman Hospital, Newcastle pieces with no loss or gain of genes – a upslanting palpebral fissure, facial balanced translocation. asymmetry and ear anomalies. David Crossland In 2004 members of the online parent Developmental delay is common and MBBS, MRCPCH support group, Chromosome 22 Central1, can be significant in infancy2. The most Consultant Cardiologist successfully lobbied to have Emanuel frequent anomalies consistent with Freeman Hospital, Newcastle syndrome added as an entry in the Online developmental delay include defects Mendelian Inheritance in Man (OMIM) affecting the midline, such as Dandy- database. Prior to this, there was concern Walker malformation; hypoplasia of the among parents about the disparate names corpus callosum, pons and cerebellar given to their children’s condition, which vermis; dilatation of the third and fourth impeded their ability to find support, eg ventricles and trigonocephaly5. Keywords supernumerary derivative 22 syndrome, Microcephaly was reported in only 23% of partial 11q trisomy, derivative 11;22 subjects in one study, while another study Emanuel syndrome; der22; congenital syndrome and partial trisomy 11;22. stated that 100% of individuals with heart defect ‘Emanuel syndrome’ was suggested by the Emanuel syndrome had microcephaly6. Key points parent group in recognition of Dr Beverly Failure to thrive is a common problem Emanuel’s cytogenetic work and her in the neonatal period and into childhood2. Zafar A., Chaudari M., Crossland D. molecular characterisation of the In neonates, poor feeding due to hypotonia Emanuel syndrome with unique cardiac chromosomal breakpoints. and the presence of cardiac and defects: a case series. Infant 2014; 10(3): 101-102. Heart defects are reported in 57% of gastrointestinal malformations are the 1. Emanuel syndrome results from an cases of Emanuel syndrome with the three most likely cause. Aside from feeding unbalanced translocation between most common defects being atrial septal issues, which are ongoing in childhood, chromosomes 11 and 22. defect, ventricular septal defect and patent recurrent infections may be partly 2. Infants with Emanuel syndrome have a ductus arteriosus2,3. Also reported are responsible for failure to thrive as these very varied clinical presentation. coarctation of the aorta, pulmonary children get older. 3. This case series considers antenatal stenosis and total anomalous pulmonary Emanuel syndrome is rare – only about diagnosis of cardiac defects and venous return4. Rare cardiac defects 200 cases have been reported in the subsequent postnatal syndromic include tetralogy of Fallot, truncus literature. Chromosome 22 Central is diagnosis. arteriosus, transposition of the great aware of approximately 500 cases 4. Diagnosis of Emanuel syndrome has a arteries and tricuspid atresia. Cardiac worldwide but it is presumed that there are profound impact on a baby’s prognosis surgery is required in 30% of those cases more cases, especially in non-English and future management. with heart malformations2. speaking countries1. The infant mortality infant VOLUME 10 ISSUE 3 2014 101 CASE REPORT rate in Emanuel syndrome is unknown, yet echocardiogram showed a deterioration in sent home on palliation at three weeks of follow-up has shown some long-term terms of a smaller RV in line with age and died within 24 hours. survival in affected children. A poor morphological monopartite ventricle. A prognosis is mostly due to central nervous univentricular repair is planned for Discussion and conclusion system problems, however current sometime in the future (the Fontan Emanuel syndrome is a very rare condition literature provides limited information on procedure) but in the meantime the infant with only a few case reports published. It is outcomes beyond the first few years of life. has been diagnosed with necrotising extremely unusual for two unrelated cases enterocolitis and has undergone surgical to present at the same hospital within a Clinical presentation treatment for this. six-month period. There have been no The two unrelated cases reported in this The infant’s parents have received reports of infants born with antenatal article presented within a six-month genetic counselling with genetic testing, diagnosis of cardiac defects and subsequent period in the same hospital in the north which showed that the mother is a carrier postnatal syndromic diagnosis, as east of England, between September 2012 of a balanced translocation between described here. According to one study, and March 2013. The infants were noted to chromosomes 11 and 22. abnormalities detected by ultrasound have dysmorphic features at birth. In both during pregnancy were only reported in cases, a genetic team was consulted and Case 2 16% of cases2, which is surprising given the chromosome testing revealed an extra The second case, a male infant of south high rate of congenital anomalies seen in chromosome containing material from east Asian origin born at 37 weeks’ this syndrome. chromosomes 11 and 22. gestation by induction of labour due to Congenital heart defects have been fetal distress, had an antenatal diagnosis of reported in the literature, ranging from Case 1 interruption of the aortic arch. A postnatal mild to severe, but there appear to be no A female Caucasian infant was born at echocardiogram revealed mitral data on the long-term prognosis for term with a birth weight of 2.8kg. Her hypoplasia, a small left ventricle, aortic children with severe cardiac defects antenatal diagnosis was pulmonary atresia hypoplasia and hypoplastic arch. The requiring palliative correction, as presented with an intact ventricular septum. This was diagnosis of hypoplastic left heart in this report. confirmed by a postnatal echocardiogram, syndrome came as a shock to the parents Diagnosis has a profound impact on which revealed a bipartite right ventricle who expected a better prognosis in light of prognosis and future management. (RV), good sized pulmonary artery and the antenatal diagnosis. Although there are no clear cut mortality confluent branch pulmonary arteries. The infant was born in a stable data for these children, a poor prognosis There was no antegrade flow across the condition and a chest X-ray showed a for this syndrome resulted in one family in pulmonary valve. A chest X-ray showed a normal sized heart and hyperaemic lung this report deciding on a palliative care normal sized heart and normal looking fields. Shortly after birth he was started on pathway. lung fields. On examination, the infant was alprostadil to maintain ductus arteriosus noted to have dysmorphic features that patency. On examination he was noted to References included ear tags, skin tags, a small chin have a small chin, a cleft palate and growth 1. Chromosome 22 Central. Emanuel syndrome and microcephaly. This prompted the restriction. There were signs of acute [Online]. Available from: www.emanuelsyndrome. genetic testing that revealed Emanuel kidney injury yet an abdominal ultrasound org/index.html [Accessed 29 April 2014]. syndrome. The infant was also noted to scan was normal. Due to excessive 2. Carter M., St.Pierre S., Zackai E., Emanuel B., Boycott K. Phenotypic delineation of Emanuel syndrome have mild hypotonia and talipes of the feet pulmonary flow the infant underwent (supernumerary derivative 22 syndrome): clinical but no genital anomalies. An pulmonary artery band insertion. He was features of 63 individuals. Am J Med Genet A 2009; ophthalmological assessment revealed a started on continuous positive airway 149A:1712-21. small eye (microphthalmia). The infant pressure (CPAP) to facilitate systemic 3. Lin A.L., Bernar J., Chin A.J. et al. Congenital heart developed mild renal failure early in the circulation by negative intrathoracic disease in supernumerary der(22), t(11;22) course of her stay at the cardiac intensive pressure. syndrome. Clin Gen 1986;29:269-75. 4. Fraccaro M., Lindsten J., Ford C.E., Iselius L. The care unit; however a renal ultrasound scan The genetic team was consulted and 11q;22q translocation: A European collaborative showed structurally normal kidneys. genetic testing revealed Emanuel analysis of 43 cases. Hum Gen 1980;56:21-51. The infant has undergone the first stage syndrome. The parents had a detailed 5. Pallotta E., Fusilli P., Ehresmann T. et al. Cerebral of palliative cardiac surgical correction, ie discussion with a geneticist, a cardiologist defects confirm midline developmental field pulmonary valvotomy. Follow-up showed a and cardiac surgeon. The different options disturbances in supernumerary der(22),t(11;22) borderline result with still no antegrade were described, ie univentricular heart syndrome. Clin Gen 1996;50:411-16. 6. Medne L., Zackai E.H., Emanuel B.S. Emanuel flow across the pulmonary valve and repair (palliative repair) with follow-up or syndrome. GeneReviews [Online]; 2010. Available moderate tricuspid regurgitation on an withdrawal of care. The parents decided on from: www.ncbi.nlm.nih.gov/books/NBK1263/ echocardiogram. The most recent a palliative care pathway. The child was [Accessed 29 April 2014].

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