Diaphragmatic herniae and translocations

Two girls with congenital diaphragmatic herniae are reported. Both were discovered to have a balanced reciprocal translocation involving 8q22.3. In one girl the translocation was de novo, in the other it was maternally inherited. Uniparental disomy was excluded in both. 8q22.3 may be the location of a gene affecting development of ihe diaphragm. (J Med Genet 1994;31:735-737) Wessex Clinical Genetics Service, Level G, Princess Anne Hospital, Coxford Road, Southampton, S09 4HA, UK I K Temple Wessex Regional Genetics Laboratory, Salisbury District Hospital, Odstock, Salisbury, SP2 8BJ, UK J C K Barber R S James Wessex Regional Paediatric Surgery, Southampton General Hospital, Tremona Road, Southampton, S09 4XY, UK D Burge Correspondence to Dr Temple. Received 14 December 1993 Revised version accepted for publication 11 May 1994 Congenital diaphragmatic hernia (DH), in which abdominal organs protrude into the thoracic cavity, arises because of abnormal development of the diaphragm. The diaphragm normally develops from four different embryological structures, the septum transversum, the oesophageal mesentery, the pleuroperitoneal membrane, and the body wall. The septum transversum makes up the majority of the diaphragm and is mesodermal in origin. The diaphragm is formed by 8 weeks of gestation. Primary failure of the septum transversum to grow is thought to result in most types of diaphragmatic herniae, including the most common type to present in the neonatal period, the posterolateral or Bochdaleck hernia. Other types, classified by the location of the defect, include the anterolateral hernia, the hiatus hernia occurring through an abnormally large oesophageal opening, and the parasternal or Morgagni hernia. The latter hernia is thought to have a different embryological cause and results from failure ofdevelopment at the costal and sternal origin of the peripheral musculature. The incidence is difficult to ascertain as a significant number of affected babies die at birth. A live birth incidence between 1 in 4000 and 1 in 10000 has been estimated.' The aetiology of this developmental defect is unknown. DH are increasingly being picked up prenatally on routine ultrasound scan but the mortality is at least 50%. Familial cases have been described, although most are sporadic. Multifactorial inheritance seems most likely.2 We present two girls who survived with diaphragmatic hernia and who were both found to have a balanced reciprocal translocation involving a breakpoint at 8q22. Case reports CASE 1 Case 1 (laboratory reference no 92/3725) was the first child of unrelated white parents. On routine ultrasound scan at 20 weeks' gestation it was shown that she had a left sided diaphragmatic hernia. No other structural abnormalities were shown. The pregnancy was otherwise normal. She was born by emergency caesarian section at 37 weeks. Birth weight was 2560 g. Surgery to correct the posterolateral diaphragmatic hernia was successful and she has since progressed normally. She sat at 8 months and was crawling by 13 months. A developmental assessment at 27 months showed her to have mild delay. Her development was assessed at a 23 month level. On physical examination her height was on the 10th centile, weight on the 3rd centile, and head circumference on the 25th centile. She was not, dysmorphic. Feeding was still a problem but she was generally healthy. A karyotype performed in utero showed case 1 to have a balanced reciprocal 8; 13 translocation and an identical translocation was found in her mother. The karyotype of case 1 was therefore 46,XX,t(8; 13) (q22.3;q22)mat (figs 1 and 2). Her father had normal chromosomes. Other family members were not tested. The mother was clinically normal but did not undergo further investigations.