Congenital diaphragmatic hernia in genetics. K.P. Cusmano¹, B.G. Kousseff². 1) Pediatrics/Genetics, University of South Florida, Tampa, FL; 2) same.

   Between 1-2-82 and 4-15-99 through the USF Genetic Clinics there were 93 probands with suspected or confirmed congenital diaphragmatic hernia (CDH) of the 35,414 probands/families evaluated. 50 were seen through the prenatal clinics. Among them were 5 in whom CDH was subsequently excluded; 3 had congenital cystic adenomatoid malformation of the lung, 1 had bronchogenic cyst, and 1 had trisomy 18. 24 survived and 26 expired including 3 miscarriages, 2 stillbirths, and 4 terminations. 34 had associated anomalies. Among these were 8 probands with Pentalogy of Cantrell, all deceased and previously reported [BDOAS 30:189-202, 1996]. The remaining 26 probands had in addition to CDH, a single defect, constellations of anomalies that were non-syndromic or syndromic CDH. The remaining 16 patients in the prenatal group had solitary CDH. 43 probands were evaluated through the pediatric genetic clinic. 17 survived and 26 died. 28 had associated abnormalities, 13 had solitary CDH. In this group there were 3 families each with first degree relatives having CDH. In one, sisters were affected; one of them had total anomalous pulmonary vein return. In the other, mother and daughter had solitary CDH. In the third, 2 brothers had CDH. This family most likely had autosomal dominant private syndrome with short stature, cleft palate, blepharophimosis, MVP, cryptorchidism, hypotonia and cardiomyopathy. Apart from the syndromic CDH there was no predilection towards a particular constellation of anomalies. Unique malformations included cyclopia, arhinia, proboscis, aphallia and blepharophimosis, all were with normal karyotypes. The syndromic CDH included 3 probands with Fryns syndrome and 1 each with Marfan, Saethre-Chotzen, Brachmann-DeLange, Ivemark, hypomelanosis of Ito, HARD, and limb-body wall syndromes. 9 patients had Pentalogy of Cantrell. CDH was found in 2 probands with trisomy 21 and in 1 each with trisomy 22 secondary to maternal translocation [11; 22], del 8p, mono 9p, del 15q and partial trisomy 1q. There were 3 maternal translocations, t [1; 9], t [11; 22] and t [7;13]. Despite having ECMO since 1993, in our experience CDH is still a high mortality genetically very heterogeneous condition without causative clues in solitary CDH.