Use of low dose computed tomography with 3D reconstructions for the prenatal evaluation of suspected skeletal dysplasia.

BACKGROUND: Sonographic evaluation of congenital skeletal dysplasias is often challenging. Ultrasound may be limited in demonstrating the skeleton and may overlook specific signs of skeletal abnormality. Computed tomography (CT) with 3D reconstruction was proposed as an aid in the diagnosis of skeletal dysplasias. OBJECTIVES: To describe our experience with 3D-CT imaging for the evaluation of suspected skeletal dysplasias. METHODS: The study group comprised 20 pregnant women carrying 22 fetuses, referred for further evaluation by CT following sonographic suspicion of fetal skeletal dysplasia at 17-39 weeks of gestation. Examinations were performed using various CT protocols. Radiation exposure was decreased during the study period, with eventual lowering of the dose to 1-3 mSv. Meticulous review of the skeleton and long bone measurements were performed on 3D reconstructions. For cases of pregnancy termination, the postmortem diagnosis was compared retrospectively with the CT findings. RESULTS: Very low dose CT protocols provided excellent diagnostic images. Of 22 fetuses suspected of having skeletal dysplasia on ultrasound, 8 were found by CT to be dysplastic and in 7 the pregnancy was terminated. Postmortem findings, when available, concurred with the CT diagnosis. The remaining 14 fetuses within this cohort were found to be normal according to CT and were carried to term. CONCLUSIONS: 3D-CT may be a valuable complimentary imaging tool to ultrasound for the diagnosis of skeletal dysplasias. With low dose protocols, this examination is relatively safe, and in the appropriate clinical context may assist in making difficult decisions prenatally.

A deleterious founder mutation in the BMPER gene causes diaphanospondylodysostosis (DSD).

Diaphonospondylodysostosis (DSD) is a rare, recessively inherited, lethal skeletal dysplasia, characterized by severe spinal ossification, segmentation defects, and renal cystic dysplasia with nephrogenic rests. We hereby present three affected individuals: two children and a fetus from two unrelated East Jerusalem Arab-Muslim families. Whereas most fetuses die in utero or perinatally, one of the children survived to 15 months. Homozygosity mapping in the two families demonstrated a single common 3.87 Mb region on chromosome 7, ruling out previously known spondylocostal/spondylothoracic dysostosis loci. The 15 protein coding genes in the region were prioritized, and some were sequenced. A single, novel deleterious mutation, Q104X, was detected in the bone morphogenetic protein-binding endothelial regulator protein (BMPER) gene, recently reported to be mutated in other DSD patients [Funari et al., 2010]. The novel mutation we identified is an ancestral founder allele, as evidenced by a shared 440 SNP haplotype, and its frequency in the general Arab population is estimated to be <1:123. Our findings confirm loss of BMPER function as a cause of axial versus appendicular skeletal defects, and suggest that less deleterious mutations may be involved in milder axial skeleton abnormalities.

Prenatal MR diffusion-weighted imaging in a fetus with hemimegalencephaly.

We report a case of hemimegalencephaly diagnosed by prenatal MRI with an emphasis on its appearance on diffusion-weighted images. This case shows that in this condition the enlarged hemisphere may show restricted diffusion on prenatal MRI. In our opinion, this finding may result from a combination of increased cellularity and advanced myelination in the affected hemisphere. Restricted diffusion is an additional valuable indicator in the analysis of the fetal brain.

Intensive management and early delivery reduce antenatal mortality in monoamniotic twin pregnancies.

BACKGROUND: Intensive management and elective delivery between 32 and 35 weeks of monoamniotic twin pregnancies were suggested as improving perinatal outcome. We sought to evaluate this management as viewed by the outcome of monoamniotic twin pregnancies in our population. METHODS: A retrospective systematic chart review of all monoamniotic twin pregnancies, diagnosed from January 1986 to June 2002, was performed in three medical centers. Demographics, pregnancy course, and perinatal outcome were evaluated. The management and outcome were compared between the group of survivors and the groups of intrauterine fetal demise (IUFD) and miscarriage. RESULTS: Thirty-three pairs of monoamniotic twins were identified. Excluded were three women, who chose to terminate the pregnancy. Total survival rate was 60% (of 60 fetuses, 36 were born alive, but one neonate died due to sepsis). None of the IUFD occurred in hospitalized patients, and two pairs of twins died after 32 weeks. In the 10 twin pairs who died in utero, cord entanglement was documented in eight (80%). There were two cases of twin discordance and two cases of twin-to-twin transfusion syndrome. One twin of the live-born group had congenital transposition of the great arteries. Furthermore, one of the hospitalized patients was delivered by means of an emergency cesarean section because of a non-reassuring non-stress test at 30 weeks. CONCLUSIONS: Women with monoamniotic twin pregnancies should be advised about the very high mortality and morbidity rate. Early diagnosis, close in-hospital antenatal surveillance starting at fetal viability, and elective delivery at 32 weeks would reduce the antenatal mortality.

Sludge ball, pseudolithiasis, cholelithiasis and choledocholithiasis from intrauterine life to 2 years: a 13-year follow-up.

OBJECTIVE: Evaluation and follow-up of infants with cholelithiasis and pseudolithiasis in a pediatric ward. PATIENTS & METHODS: Prospective study from April 1990 to October 2003 identified hospitalized infants younger than 2 years with ultrasonographic findings of cholelithiasis, choledocholithiasis or pseudolithiasis. Associated abnormalities or contributory factors were recorded and patients were followed for from 6 months to 13 years (mean, 4 years). RESULTS: Thirty-four patients were diagnosed between the age of 3 weeks and 24 months. Thirteen (38%) had been treated with third-generation cephalosporins. Other associated factors were dehydration in 10 (29%), urinary tract infection in two (6%) and one each for cholestatic liver disease, total parenteral nutrition, immunoglobulin A deficiency and prematurity. Six infants (17%) had no known risk factor. Six additional patients were diagnosed by antenatal ultrasound. CONCLUSIONS: Cholelithiasis in infants hospitalized for a variety of common pediatric conditions is not rare. Dehydration and treatment with third-generation cephalosporins are important associated factors. The classic risk factors of hemolysis and previous gastrointestinal surgery, were not found in our group. The overall prognosis was good. Pseudolithiasis disappeared in all infants. Of the 21 infants with cholelithiasis, only two developed cholecystitis. In nine infants, spontaneous resolution occurred. In the absence of other clinical or imaging evidence of biliary tract disease, conservative management is advised.

Absent ductus venosus in the fetus: review of the literature and first report of direct umbilical venous drainage to the coronary sinus.

The ductus venosus connects the portal and umbilical veins with the inferior vena cava and acts as a sphincter to protect the fetus from placental overcirculation. Its absence usually causes hydrops fetalis and is associated with high mortality rate, chromosomal anomalies and congenital malformations. In this condition, the umbilical vein almost always drains directly into right-sided structures such as inferior vena cava or right atrium. We reviewed the literature and describe the first case of a fetus with absent ductus venosus and direct connection of the umbilical vein to the coronary sinus.

Extreme caudal agenesis. Possible drug-related etiology?

BACKGROUND: Caudal regression syndrome (CRS) is a rare anomaly of the lower body pole that represents a continuum of congenital malformations ranging from isolated sacral agenesis to absence of the lumbosacral spine and major visceral anomalies. While the exact etiology of this syndrome is unclear, maternal diabetes, genetic factors, teratogens and vascular anomalies altering blood flow have been hypothesized to play a role in its pathogenesis. CASE: A fetus had extreme hypotrophy of the caudal body pole, aplasia of the lower spine and complete renal agenesis diagnosed in the second trimester by ultrasound. Maternal history revealed the use of minoxidil solution for preventing hair loss for four years prior to and during gestation. Also, the mother had taken trimethoprim-sulfamethoxazole during the first trimester for treatment of upper respiratory disease. No maternal diabetes or history of familial genetic diseases was evident. CONCLUSION: In an extreme form of CRS consisting of complete aplasia of the lower body pole and viscera and additional malformations, a possible drug-related etiology was suggested but should be confirmed by more studies.