In Utero Diagnosis of Niemann-Pick Type C in the Absence of Family History.

Niemann-Pick type C (NPC) disease is a recessive disorder that results in unesterified cholesterol accumulating in the lysosomal and late endosomal system. It is caused by mutations in NPC1 or NPC2 genes and leads to systemic and neurodegenerative symptoms. Few cases of prenatal presentation of NPC have been reported and only two cases in the absence of previous family history, indicating the diagnosis is particularly difficult in such a situation. We report a prenatal diagnosis of NPC in a couple without family history. An ultrasound screening at 22 weeks of gestation (WG) detected fetal ascites and hepatomegaly, which were still present at 25, 27, and 29 WG, and a splenomegaly progressively appeared. No placentomegaly or other signs of hydrops fetalis were observed. The diagnostic of NPC was prenatally confirmed by a filipin test and NPC1 sequencing and multiplex ligation-dependent probe amplification assay which revealed a maternal missense mutation (c.2608T>C; p.Ser870Pro) and a paternal deletion of exons 5 to 25. This additional prenatal case of NPC suggests that even in the absence of family history, fetal ascites associated with splenomegaly but no hydrops should nonetheless arouse suspicion concerning this disease as a possible diagnosis.

Fetal intracerebral hemorrhage and cataract: think COL4A1.

The COL4A1 gene encodes the alpha1 chain of type IV collagen, a crucial component of nearly all basement membranes. Mutations in COL4A1 were first associated with cerebral microangiopathy and familial porencephaly. Recently, several authors have reported mutations in COL4A1 as a Mendelian cause of prenatal onset intracranial hemorrhage (ICH). We report two cases of prenatal ICH associated with cataract and suggest that COL4A1 mutation should be envisaged in fetuses with prenatal ICH, especially in the presence of lens abnormalities at ultrasound examination.

Binder phenotype in mothers affected with autoimmune disorders.

OBJECTIVE: To report four foetal cases of the Binder phenotype associated with maternal autoimmune disorders. PATIENTS AND METHODS: In three mothers with autoimmune diseases, 2D and 3D ultrasonographic measurements were made on four foetuses with the Binder profile, and were compared with postnatal phenotypes. RESULTS: The Binder phenotype can be detected in early pregnancy (14.5 WG). All foetuses had verticalized nasal bones and midfacial hypoplasia. Punctuate calcifications were found in almost all the cases. No specific maternal auto-antibody has been associated with foetal Binder phenotype. CONCLUSION: Since the Binder phenotype can be diagnosed at ultrasound examination during pregnancy, it is important to establish the underlying cause so as to assess the foetal prognosis. This study stresses the importance of systematic checks for maternal autoimmune disease in cases of prenatally diagnosed Binder phenotypes.

[Linear insertion of atrioventricular valves (Livav): echocardiographic diagnosis, reliability and prevalence in the general population]. / Insertion linéaire des valves auriculoventriculaires (Ilvav): fiabilité du diagnostic échographique et prévalence dans une population sans trisomie 21.

OBJECTIVES: Assess the reliability of prenatal diagnosis of linear insertion of atrioventricular valves (Livav) by echocardiography as well as estimate Livav's prevalence in a population without Down syndrome. PATIENTS: One hundred and twenty-three fetuses of whom 113 were explored before and after birth and 631 consecutive out-patients explored in cardiopediatric unit. METHODS: Determination of the likehood ratio (LHR+ and LHR-) of Livav prenatal diagnosis. Evaluation of the consistency between pre- and postnatal diagnoses as well as between two observers after birth (Kappa index). Prevalence study according to the presence of Down syndrome, cardiac malformation or others abnormalities. RESULTS: LHR+ value was 6.17 and LHR- value was 0.30 for echographic Livav prenatal diagnosis. Consistency was low between pre- and postnatal diagnoses (Kappa = 0.57) and higher between two observers after birth (Kappa = 0.79). Livav prevalence was 2 to 5% in a population without Down syndrome but 15% when associated with a cardiac malformation. Seventy-eight percent Down syndromes had either Livav or AVSD. CONCLUSION: Livav echographic prenatal diagnosis is difficult, for it generates many false positives. Livav is not specific of Down syndrome and can be found relatively frequently in other subjects.

[Prevention of spontaneous preterm birth in asymptomatic twin pregnancies]. / Prévention de la prématurité spontanée chez les grossesses gémellaires asymptomatiques.

OBJECTIVES: To determine prenatal methods to predict and prevent spontaneous preterm birth in asymptomatic twin pregnancies. METHODS: Articles were searched using PubMed, Embase and Cochrane library. RESULTS: Uterine activity monitoring and bacterial vaginosis screening are not useful to predict preterm birth (EL2 and EL3 respectively). Current literature data are contradictory and insufficient to determine whether fetal fibronectin and digital cervical assessment are predictors of preterm birth. History of preterm birth (EL4), and cervical length measurement by transvaginal ultrasonography (EL2) predict preterm birth. Nevertheless, there are no intervention studies that have evaluated cervical length measurement in the prevention of preterm birth. Hospital bedrest, prophylactic tocolytic and progesterone therapy, and prophylactic cervical cerclage in patients with or without short cervix have not been shown to be effective in preventing preterm birth. CONCLUSIONS: Prenatal methods to prevent spontaneous preterm birth in asymptomatic twin pregnancies are currently very limited.

Influence of ultrasonographers training on prenatal diagnosis of congenital heart diseases: a 12-year population-based study.

OBJECTIVE: Since 1998, French multidisciplinary prenatal diagnosis centers (CPDPN) offer a training opportunity to first-level screening sonographers. This study measures the impact of this training on prenatal detection rates of congenital heart diseases (CHDs). METHODS: We analyzed the sensitivity of screening sonographers by comparing CHD prenatal diagnoses and CHDs observed after birth in the area of Angers from 1994 to 2006. Two groups of sonographers were compared, those who attended the training (n=19) and those who did not (control group. n=21). The evolution of CHD detection rate was compared between two successive periods of 6 years each. RESULTS: Of 947 CHDs, 438 (46%) were detected prenatally. The control group sensitivity was 16 versus 37% for the sonographers who had attended the training course (p<0.001).Between the two study periods, detection rates for all CHDs and significant CHDs remained unchanged in the control group, whereas they improved significantly in the other group (respectively 54% vs 33% and 75% vs 38%, p<0.05). CONCLUSION: This study supports the hypothesis of a beneficial effect of CPDPN on prenatal diagnosis of CHDs. These centers not only fulfill their primary purpose but also operate as learning centers in which screening sonographers may improve their practice.

Prenatal diagnosis of absence of the septum pellucidum associated with septo-optic dysplasia.

Septo-optic dysplasia (SOD; De Morsier syndrome) is a rare congenital disorder characterized by the absence of the septum pellucidum (SP), hypoplasia of the optic chiasma and nerves, and various types of hypothalamic-pituitary dysfunction. We report on two fetuses with absence of the SP diagnosed by ultrasound examination at 29 and 30 gestational weeks. In the first case the diagnosis of SOD was suspected in utero and confirmed postnatally; to the best of our knowledge this is the first report of the prenatal diagnosis of SOD. In the second case absence of the SP appeared to be isolated and no visual or endocrine impairment were detected after birth.