Alagille syndrome with deletion 20p12.2-p12.3 and hypoplastic left heart

We report a male patient born at 37-weeks gestation, weighing 1.885 kg (<0.4th centile). Shortly after birth, he was diagnosed with hypoplastic left heart syndrome for which he underwent a Norwood procedure. Subsequently, he developed problems with failure to thrive and developmental delay. At the age of 4 years his delay in growth and development led to further investigations, which revealed a small de-novo interstitial deletion of chromosome 20p12.2. JAGGED1 haploinsufficiency was confirmed by fluorescence in situ hybridization. Array-comparative genomic hybridization analysis confirmed and quantified an approximate 5.4 Mb interstitial deletion involving the chromosomal region 20p12.2-p12.3. This precise interstitial deletion has not been previously reported. Further clinical evaluation revealed posterior embryotoxon and butterfly vertebrae. He has normal liver function tests, facial features consistent with Alagille syndrome, and mild learning difficulties. To our knowledge this is the first report of Alagille syndrome associated with hypoplastic left heart syndrome.     

Outcome of infants with hypoplastic left heart and Turner syndromes

OBJECTIVE: To report the obstetric and neonatal outcomes of ten infants with hypoplastic left heart syndrome in association with Turner syndrome. METHODS: The Pediatric Cardiovascular Surgery database at the University of Michigan was searched from 1990 to 1997, and obstetric and neonatal records of neonates with hypoplastic left heart syndrome and Turner syndrome were reviewed. RESULTS: There were 406 cases of hypoplastic left heart syndrome admitted during 8 years, of which ten (2.5%) also had Turner syndrome. Nine infants were delivered at term and one at 36 weeks. The mean (+/- standard deviation [SD]) gestational age at delivery was 38 +/- 1.2 weeks, and mean (+/-SD) birth weight was 2991 +/- 438 g. Delivery was vaginal in all cases, and no infant had an Apgar score at 5 minutes less than 7. Karyotype was 45, X in seven cases, and 45, X mosaic in three. Most infants had dysmorphic features at birth. All ten infants had first-stage reconstruction surgery for hypoplastic left heart syndrome. Only two survived and underwent second-stage palliation; both are alive currently, although with significant medical problems. CONCLUSION: For infants with hypoplastic left heart and Turner syndromes, regular obstetric management appears appropriate. Although staged reconstruction surgery has improved survival for neonates with isolated hypoplastic left heart syndrome, for those with Turner syndrome, survival appears markedly reduced.     

Assessment of physician directiveness: using hypoplastic left heart syndrome as a model.

OBJECTIVE: To test the hypothesis that surgeons are more directive than pediatricians in discussions with parents of critically ill children. STUDY DESIGN: We designed a novel tool to assess physician directiveness in discussions with parents of children with hypoplastic left heart syndrome. We sent surveys containing the assessment tool as well as demographic questions to all attending physicians in Neonatology, Pediatric Critical Care, Pediatric Cardiology, and Congenital Cardiac Surgery at 14 of the largest pediatric cardiac surgery centers in the United States. Responses to the tool were used to determine a "directiveness score" for each physician. We then performed univariate and multivariable linear regression analyses to assess the association of physician specialty, race/ethnicity, religion, gender, and years in practice with the directiveness score. RESULTS: Responses from 138 physicians were analyzed. In univariate analyses, with neonatologists as the reference group, surgeons were most directive (regression coefficient 3.02, 95% confidence interval 0.69 to 5.35, P=0.01), followed by cardiologists (regression coefficient 1.67, 95% confidence interval 0.13 to 3.20, P=0.03). No other variable was associated with physician directiveness score. These results were similar in the multivariable analysis. CONCLUSIONS: These results suggest that physician specialty is associated with directiveness. It is unclear, however, what amount of direction parents of critically ill children prefer.     

Endoscopic ligation of umbilical cord at 19 week's gestation in monoamniotic monochorionic twins discordant for hypoplastic left heart syndrome

We report the first attempt of reduction of monoamniotic twins, discordant for hypoplastic left heart syndrome, using a new fetoscopic technique. Employing sonographic guidance and endoscopic visualization, cord ligation was accomplished, but significant cord entanglement, not previously appreciated, resulted in the ligation of the umbilical cord of the normal fetus. Cord entanglement may frustrate endoscopic techniques in monoamniotic twins.     

Fetal megalourethra associated with hypoplastic left heart and imperforate anus: a previously unreported association

We report two cases of a fetus with a megalourethra associated with a hypoplastic left heart, dilated and echogenic bowels, vesico-colonic fistula and an imperforate anus. This combination of fetal abnormalities may represent an unclassified syndrome.     

Successful selective termination at 17 weeks' gestation in monochorionic monoamniotic twin pregnancy affected by twin-twin transfusion syndrome and discordant for hypoplastic left heart syndrome

OBJECTIVES: To report a successful selective feticide in a complicated monochorionic monoamniotic (MCMA) pregnancy. METHODS: A case of MCMA pregnancy with severe twin-twin transfusion syndrome and discordant for hypoplastic left heart syndrome was diagnosed at 16 weeks' gestation. A complete ultrasound and fetoscopic surveillance was performed, ruling out cord entanglement and, thus, precluding the necessity of transecting the cord. RESULTS: The selective feticide was successfully performed by bipolar coagulation of the umbilical cord of the abnormal fetus under ultrasound guidance. The survivor twin developed normally during the rest of the pregnancy and was born at term. At 6 months of age, the infant was healthy. CONCLUSION: Selective feticide in complicated monoamniotic pregnancies can be safely performed. Cord entanglement can be confidently excluded by both ultrasound and fetoscopy, thus making the systematic transection of the umbilical cord unnecessary.     

Plasma atrial natriuretic peptide in fetuses with cardiac disease

OBJECTIVE: To investigate atrial natriuretic peptide (ANP) levels in fetuses with cardiac defects and to evaluate the relationships between plasma ANP levels and the presence of polyhydramnios. METHODS: Plasma ANP levels were measured by radioimmunoassay in 27 fetuses with cardiac abnormalities and in 14 normal healthy fetuses. RESULTS: Fetal plasma ANP levels were similar in the two studied groups (p = 0.18) but they were significantly higher in a subset of cases with cardiac disease and polyhydramnios (n = 7) than in those with cardiac disease and normal amniotic fluid (n = 20; p = 0.036) and controls (p = 0.01). CONCLUSION: Polyhydramnios in fetuses with heart conditions might be explained by increased fetal diuresis secondary to increased ANP production.     

Prenatal diagnosis of hypoplastic left ventricle

A case of prenatal diagnosis of hypoplastic left ventricle by means of echocardiography is presented. The method of detecting this syndrome is described and the importance of its prenatal diagnosis emphasized.     

Long-bone growth in fetuses with Down syndrome

Short stature is a well-recognized component of Down syndrome. The femur lengths of affected fetuses have been observed to be shorter than normal, with a ratio of actual to expected femur length of less than 0.91 indicating a high risk of trisomy. To further evaluate this finding we have determined the relationship between limb lengths and gestational age in 37 postmortem fetal specimens with trisomy 21. Control values were obtained from 174 normal fetuses. Measurements of the femur, tibia, fibula, humerus, radius, and ulna were made from roentgenograms or by direct measurement of the bone. Most measurements for each bone of the affected fetuses fell below the normal regression line for that bone, but only 3/37 femurs, 4/32 tibias, 5/32 fibulas, 9/32 humeri, 10/32 radii, and 7/32 ulnas fell more than 2 SDs below the mean. The ratios of actual to expected femur lengths were computed and six fetuses with Down syndrome (16.2%) had ratios less than 0.91. The bones of the extremities of fetuses with trisomy 21 are shorter than normal, but the differences are relatively small. The ratio of actual/expected femur lengths was a less efficient predictor of Down syndrome than were either maternal age or maternal serum alpha-fetoprotein tests. The upper extremity bones were shorter than normal more often than were the bones of the lower extremity, and this finding should be explored further in a prospective study.     

Huge pericardial rhabdomyoma with hypoplastic left ventricle and lung

We describe the clinical course and autopsy findings of a female fetus with hydrops fetalis due to a huge pericardial rhabdomyoma. Fetal echocardiography at 21 weeks gestation demonstrated a huge tumor in the left ventricle. The fetus died of hydrops fetalis due to cardiac dysfunction at 24 weeks gestation. Autopsy demonstrated that the tumor protruded from the epicardial region of the apex into the pericardial cavity and induced a hypoplastic left ventricle and lung. Microscopically, the cardiac tumor showed characteristics of rhabdomyoma. This localization of cardiac rhabdomyoma is rare, but we remain aware of the possibility of an unusual and rapid progression of cardiac rhabdomyoma.