Outcome of partial agenesis of corpus callosum.

BACKGROUND: The diagnosis of corpus callosum anomalies by prenatal ultrasound has improved over the last decade because of improved imaging techniques, scanning skills, and the routine implementation of transvaginal neurosonography. OBJECTIVE: Our aim was to investigate all cases of incomplete agenesis of the corpus callosum and to report the sonographic characteristics, the associated anomalies, and the perinatal outcomes. STUDY DESIGN: We performed a retrospective analysis of cases from January 2007 to December 2017 with corpus callosum anomalies, either referred for a second opinion or derived from the prenatal ultrasound screening program in a single tertiary referral center. Cases with complete agenesis were excluded from the analysis. Standardized investigation included a detailed fetal ultrasound including neurosonogram, fetal karyotyping (standard karyotype or array comparative genomic hybridization) and fetal magnetic resonance imaging. The pregnancy outcome was collected, and pathologic investigation in case of termination of the pregnancy or fetal or neonatal loss was compared with the prenatal findings. The pregnancy and fetal or neonatal outcomes were reported. The neurologic assessment was conducted by a pediatric neurologist using the Bayley Scales of Infant Development-II and the standardized Child Development Inventory when the Bayley investigation was unavailable. RESULTS: Corpus callosum anomalies were diagnosed in 148 cases during the study period, 62 (41.9%) of which were excluded because of complete agenesis, and 86 fetuses had partial agenesis (58.1%). In 20 cases, partial agenesis (23.2%) was isolated, whereas 66 (76.7%) presented with different malformations among which 29 cases (43.9%) were only central nervous system lesions, 21 cases (31.8%) were non-central nervous system lesions, and 16 cases (24.3%) had a combination of central nervous system and non-central nervous system lesions. The mean gestational age at diagnosis for isolated and non-isolated cases was comparable (24.29 [standard deviation, 5.05] weeks and 24.71 [standard deviation, 5.35] weeks, respectively). Of the 86 pregnancies with partial agenesis, 46 patients opted for termination of the pregnancy. Neurologic follow-up data were available for 35 children. The overall neurologic outcome was normal in 21 of 35 children (60%); 3 of 35 (8.6%) showed mild impairment and 6 of 35 (17.1%) showed moderate impairment. The remaining 5 of 35 (14.3%) had severe impairment. The median duration of follow-up for the isolated form was 45.6 months (range, 36-52 months) and 73.3 months (range, 2-138 months) for the nonisolated form. CONCLUSION: Partial corpus callosum agenesis should be accurately investigated by neurosonography and fetal magnetic resonance imaging to describe its morphology and the associated anomalies. Genetic anomalies are frequently present in nonisolated cases. Efforts must be taken to improve ultrasound diagnosis of partial agenesis and to confirm its isolated nature to enhance parental counseling. Although 60% of children with prenatal diagnosis of isolated agenesis have a favorable prognosis later in life, they often have mild to severe disabilities including speech disorders at school age and behavior and motor deficit disorders that can emerge at a later age.

Postmortem MR in termination of pregnancy for central nervous system (CNS) anomalies.

OBJECTIVES: To evaluate the concordance of conventional autopsy (CA) and postmortem magnetic resonance (MR) after termination of pregnancy (TOP) in fetuses with prenatally detected central nervous system (CNS) anomalies. Second, to determine the most informative postmortem investigation in parental counseling. METHODS: All TOPs between 2006 and 2016 with prenatally detected CNS involvement and having a postmortem MR and CA as postmortem examinations were retrospectively analyzed and concordance levels were established. RESULTS: Of 764 TOPs, 255 cases had a CNS anomaly detected prenatally (33.4%). Fetal genetic anomalies (n = 40) and cases without both postmortem MR and CA were excluded, leaving 68 cases for analysis.Disagreement between postmortem MR and CA was observed in 22 cases (32.4%). In eight cases (11.8%), more information was obtained by CA compared with MR. However, only two cases with major additional findings were found when compared with prenatal diagnosis. In 14 cases (20.6%), MR was superior to CA either because of additional cerebral anomalies undetected by CA (n = 5) and/or because of severe autolysis hindering pathology of the CNS (n = 9). CONCLUSIONS: Our data point out that an adequate postmortem evaluation, valuable in parental counseling, can be provided by a postmortem MR in 97% of the cases.Key PointsAn adequate postmortem evaluation, valuable in parental counseling, can be provided by a postmortem (PM) magnetic resonance (MR) in the majority of cases.PM MR is an excellent postmortem imaging tool for the brain.In cases with brain autolysis, PM MR is often the only informative PM investigation tool.PM MR is an essential adjunct to CA in the PM evaluation of pregnancies terminated for a central nervous system (CNS) anomaly.

Prenatal diagnosis of middle interhemispheric variant of holoprosencephaly: review of literature and prenatal case series.

OBJECTIVE: Middle interhemispheric (MIH) variant of holoprosencephaly (HPE) or syntelencephaly is a rare prosencephalic cleavage disorder. In literature, few cases of accurate prenatal diagnosis have been reported. We report on four additional prenatally diagnosed cases. METHODS: Between 2012 and 2017, four cases of MIH HPE were retrieved. Data on prenatal imaging, genetic analysis, and pathological investigation are collected. A "PubMed" and "Trip database" search were conducted revealing six papers reporting on 11 prenatally diagnosed cases. RESULTS AND DISCUSSION: Four additional cases of MIH HPE were diagnosed at an earlier gestational age (between 17 and 25 weeks of gestation) compared with 11 cases from the literature review (15-39 weeks). First trimester transvaginal ultrasound facilitates correct differentiation between the severe HPE variants. Frequent association with ZIC2 mutation was found in nearly 50% of the cases (5/11) compared with one case in our series. CONCLUSIONS: MIH variant of HPE is detectable from the early second trimester and should be considered in the differential diagnosis when the cavum septi pellucidi (CSP) is absent. Genetic analysis and autopsy should be conducted to investigate this more recent and rare variant.

Novel STIL Compound Heterozygous Mutations Cause Severe Fetal Microcephaly and Centriolar Lengthening.

STIL (SCL/TAL1 interrupting locus) is a core component of the centriole duplication process. STIL mutations have been associated with both autosomal recessive primary microcephaly (MCPH) and holoprosencephaly. In this report, we describe a family with multiple miscarriages and 2 terminations of pregnancy due to marked fetal microcephaly, delayed cortical gyrification, and dysgenesis of the corpus callosum. Whole exome sequencing allowed us to identify novel compound heterozygous mutations in STIL. The mutations lie, respectively, in the CPAP/CENPJ and the hsSAS6 interacting domains of STIL. M-phase synchronized amniocytes from both affected fetuses did not display an aberrant number of centrioles, as shown previously for either STIL-depleted or overexpressing cells. However, we observed an elongation of at least 1 centriole for each duplicated centrosome. These preliminary results may point to a novel mechanism causing MCPH and embryonic lethality in humans.

Mutations in CEP120 cause Joubert syndrome as well as complex ciliopathy phenotypes.

BACKGROUND: Ciliopathies are an extensive group of autosomal recessive or X-linked disorders with considerable genetic and clinical overlap, which collectively share multiple organ involvement and may result in lethal or viable phenotypes. In large numbers of cases the genetic defect remains yet to be determined. The aim of this study is to describe the mutational frequency and phenotypic spectrum of the CEP120 gene. METHODS: Exome sequencing was performed in 145 patients with Joubert syndrome (JS), including 15 children with oral-facial-digital syndrome type VI (OFDVI) and 21 Meckel syndrome (MKS) fetuses. Moreover, exome sequencing was performed in one fetus with tectocerebellar dysraphia with occipital encephalocele (TCDOE), molar tooth sign and additional skeletal abnormalities. As a parallel study, 346 probands with a phenotype consistent with JS or related ciliopathies underwent next-generation sequencing-based targeted sequencing of 120 previously described and candidate ciliopathy genes. RESULTS: We present six probands carrying nine distinct mutations (of which eight are novel) in the CEP120 gene, previously found mutated only in Jeune asphyxiating thoracic dystrophy (JATD). The CEP120-associated phenotype ranges from mild classical JS in four patients to more severe conditions in two fetuses, with overlapping features of distinct ciliopathies that include TCDOE, MKS, JATD and OFD syndromes. No obvious correlation is evident between the type or location of identified mutations and the ciliopathy phenotype. CONCLUSION: Our findings broaden the spectrum of phenotypes caused by CEP120 mutations that account for nearly 1% of patients with JS as well as for more complex ciliopathy phenotypes. The lack of clear genotype-phenotype correlation highlights the relevance of comprehensive genetic analyses in the diagnostics of ciliopathies.

Prenatal diagnosis of MPPH syndrome.

We report the prenatal sonographic detection of a fetus with megalencephaly, polymicrogyria, postaxial polydactyly and hydrocephaly. Only 14 patients have been reported in the literature so far, all but one were diagnosed postnatally. The polymicrogyria in the frontoparietal lobe was confirmed by prenatal magnetic resonance imaging. Additionally, a hypoplastic thymus as seen in a 22q11 deletion was present. Although polymicrogyria along with pre-axial polydactyly has been described in 22q11 deletion, the diagnosis of Di George syndrome was ruled out. The etiology of megalencephaly, polymicrogyria, postaxial polydactyly and hydrocephaly has not been revealed yet. A dominant as well as recessive inheritance has been suggested.

Creatine kinase as an indicator for hysterectomy in postpartum endomyometritis due to group A streptococci: a hypothesis illustrated by a case report.

BACKGROUND: Puerperal group A streptococcus (GAS) infection, once the leading cause of postpartum sepsis, has been increasing again since the 1980s. Streptococcal toxic shock syndrome (STSS) is a serious complication characterized by rapidly spreading GAS infection, shock, and multiple organ failure. Immediate recognition and implementation of therapy is crucial for survival. Making informed decisions regarding surgical debridement, namely hysterectomy, based on clinical indicators is difficult for practitioners. OBJECTIVES: This article discusses the potential role of creatine kinase in the decision-making process for treatment of STSS, particularly with regard to hysterectomy. MATERIAL AND METHODS: A case report is presented. The literature was searched using the key words 'group A streptococcus', 'postpartum hysterectomy', 'creatine kinase', 'endomyometritis', and 'streptococcal toxic shock syndrome' in PubMed and the UptoDate database. Relevant articles published between 1991 and 2011 were evaluated. CONCLUSION: Decisions regarding hysterectomy in STSS management are difficult. A rise in CK levels in the serum may indicate involvement of the myometrium and may be an important parameter in the difficult decision of hysterectomy when treating STSS.