Aims:  It is frequently stated that the majority of stillbirths are unexplained ( 70%).  This figure is derived using the Wigglesworth classification and would be considerably reduced if alternative classification systems were used, particularly those including a category for placental disease.  The purpose of study was to compare  five classification systems, with particular reference to the ‘unexplained’ rate.

Methods:  Retrospective study of autopsy reports of stillbirths in Northern Ireland in 1999 and 2009.  The death was classified according to following systems – Wigglesworth, ReCoDe, PZANZ, Tulip, Fetal and Neonatal classification ( CEMACE).  The strengths, weaknesses and ease of application were compared. Differences in results between the two years were examined.

 Results:  The reports of all 115 stillbirth postmortems were reviewed.  Unexplained stillbirths accounted for 71% of cases in Wigglesworth classification, 29% in Tulip, 19% in PZANZ, 18.2% in ReCoDe and nil in CEMACE.  In all classifications 14.8% of stillbirths were due to congenital anomalies.  A placental category was present in only two classifications yet accounted for 44.3% of stillbirths in Tulip and 37.4% in ReCoDe.  Intrauterine infection as a cause of stillbirth varied according to diagnostic criteria– 6.9% when positive microbiology required, 20.9% in CEMACE classification.  Comparison of 1999 and 2009 showed an increase in stillbirths attributed to infection and a reduction in those with congenital anomalies in 2009. 

 Conclusion:  Lack of concordance between classification systems suggests that one which includes a separate category for placental disease and uses microbiological or histological criteria for intrauterine infection is essential.

The aim of this study is to show the importance of placental examination for the diagnosis of major alpha thalassemia and to conduct the genetic testing. The 22WG US of this 23 year old primigravida Chinese patient showed  cardiomegaly, IUGR and large placenta.  At 29WG, C-section was perform in emergency because of preeclampsia and suspicion of basal hematoma. The male newborn, weighted 1460g, APGAR 2/10, was unresponsive to treatments in the ICU and died at 7 hours. The placenta was send for pathological examination with a suspicion of storage disease. On gross examination, the placenta weighted 4 times the normal weight expected (1000g /270g). Tissue sections showed an heterogeneous placental parenchyma. On microscopic examination, the placenta was similar in all samples: large villi, chorioangiosis and major erythroblastosis with numerous bastes within the fetal capillaries suggesting a severe anemia or a fetal leukemia. Sickle cells were observed within fetal capillaries. These placental lesions in a context of IUGR and preeclampsia in a Chinese patient prompted us to diagnose major alpha thalassemia. Major alpha thalassemia, an autonomic recessive genetic disorder by deletion of the 4 genes of the alpha globin induces a mirror syndrome characterized by in the fetus, profound anemia, cardiomegaly and hydrops incompatible with life ; in the mother, a large placental with severe preeclampsia. This association in patients from South-Est Asia should prompt the pathologist to diagnose major alpha thalassemia and to conduct the genetic testing. In this case, alpha globin gene testing on stored amniotic cells confirmed the pathological diagnosis.

Aims:  To compare and contrast stillbirth autopsies carried out in Northern Ireland in 1999 and 2009 with particular reference to infection and IUGR as it was anecdotally felt that both are now diagnosed with greater frequency.

 Methods:  The reports of the 61 stillbirths who had post-mortem examination in 1999 and 55 in 2009 were reviewed.  The required information was recorded in tabulated form. 

 Results:  The Stillbirth rate in Northern Ireland fell from 5.7 to 4.7 and PM rate rose from 46% to 55%. The spread of gestational age over categories 24 - 29+6, 30 - 36+6 and 37 - 40+6 weeks was relatively even in both cohorts.  In 1999 15 cases (25 %) were 37+ weeks gestation and in 2009 only 6 cases (11%).  In 1999 the largest maternal age group was 25-30 years and in 2009 31-36 years.  In 1999 – 67% primigravida, 88% singleton, 2009 – 55% primigravida, 96% singletons.  In 1999 the cause of stillbirth was recorded as intrauterine infection in 15% of cases and 15% of stillbirths were growth restricted.  In the 2009 cohort these figures had risen to 29% and 32% respectively.  Of stillbirths >37 weeks 70% had intrauterine infection in 2009, having risen from 14.75 % a decade earlier.

 Conclusions: This small study confirms that both intrauterine infection and IUGR are diagnosed with greater frequency in our region than a decade ago.

Pregnancy in a 31 year old lady with sickle cell trait was complicated by severe pre-eclampsia and intra-uterine growth restriction, resulting in delivery by Caesarean section at 27 weeks.  The newborn was anaemic, with excess nucleated red cells, consistent with a response to blood loss or peripheral destruction of red cells. Blood transfusion led to full recovery.  Kleihauer test was not done as the mother was Rh pos.

Gross examination of the placenta revealed discrete haemorrhagic lesions measuring up to 10 mm.

On histology, several haematomas were identified, some being layered intervillous haematomas at the centres of lobules, with adjacent viable villi.  Others were centred on the maternal surface and were composed of central areas of haemorrhage with surrounding rims of infarcted villi and intervillous fibrin.

The mother’s sickle trait allowed characterisation of the lesions. The hypoxic state of the separated placenta after delivery caused entrapped deoxygenated maternal red cells to sickle, whereas deoxygenated fetal red cells retained their normal morphology. This observation presented an opportunity to study the composition of the vascular lesions, in that it demonstrated which were fetal which were of maternal origin. It was observed that the intervillous haematomas were composed of normal fetal red cells, but the haemorrhages within infarcts were maternal sickled red cells.   There were no fetal nucleated red cells in the placental fetal vessels or the haemorrhages.  These findings suggest that the cause of postnatal anaemia could be fetal haemorrhage into the maternal intervillous space.

Introduction:Walker Warburg Syndrome (WWS) is a lethal, genetically heterogeneous autosomal recessive disorder characterized by Type II lissencephaly (Cobblestone lissencephaly), retinal malformation, cerebellar malformation, and congenital muscular dystrophy.

Objective: The neuropathological findings at autopsy in five cases of type II lissencephaly are presented.

Case reports: We report the autopsy findings of 5 cases, two of them are a siblings referred to pathology department for major hydrocephalus discovered on ultrasound between 20 and 22 gestational weeks in 3 cases and at 37 Weeks for the two others. Hydrocephalus was associated with occipital encephalocele in one case and with 4^th ventricle cyst suggesting a Dandy-Walker malformation in the other case. Medical termination of pregnancy was performed at 22 Weeks in 3 cases. For the two others, one was stillborn at term and the other died few hours after birth. Pathology findings in all cases showed lissencephaly, hydrocephalus, diffuse and severe cerebral and cerebellar cortical dysplasia with glial and neuronal displacement into the leptomeninges.

Conclusion: Fetal  hydrocephalus was the major manifestation leading to the prenatal detection of this syndrome. Our  cases are highlighting the necessity  to look for  associated anomalies in fetuses or newborn infants with hydrocephalus in order to establish a better prenatal diagnosis and genetic counseling.

Background: Dyssegmental dysplasia is an autosomal recessive lethal disorder, originally considered as a Kniest-like skeletal dysplasia with campomelia.It is linked to functional null mutations of the perlecan gene (HSPG2) located on chromosome 1p36.1-35. We report the first case diagnosed in our department.

 Materials and methods: 31 year old mother, G1 P0 , non consanguineous with her husband, given a 15-16 weeks-aged foetus with dwarfism and dyssegmental dysplasia detected prenatally by ultrasonography. A medical termination of the pregnancy was indicated. Radiographic and autopsy were performed.

Results: External examination showed a facial dysmorphy,  thick neck, pterygia and micromelia with angulations of limbs, chest narrowing and an abducted hallux in the right foot. No anomaly in visceral examination. The radiographics showed short limbs with Kniest-like large metaphyses, bowing of long bones and pleomorphic vertebral bodies with irregular segmentation and absent ossification of pelvic bones. The cranial vault was normal.

Histologically, the resting cartilage showed scattered, large puddle-like spaces. The physeal growth zones are disorganized.

Conclusion: Prenatal diagnosis is useful to detect this type of skeletal anomaly in order to indicate medical termination of the pregnancy earlier. fetopathological examination with  skeletal radiographics  are mandatory in order to establish a precise diagnosis allowing a suitable genetic counselling.

Intradural and thin subdural haemorrhages are frequently seen in perinatal autopsies. There is some controversy surrounding their association with hypoxic ischaemic encephalopathy (HIE) in infants and young children.

Methods: We conducted an audit of the post mortem reports of infants and young children (0-3 years)  over a period of 3 years (RLH) and 4 years (SCH). Intradural haemorrhage (IDH) was classified as negative, microscopic only and macroscopic. HIE was considered negative, early (oedema and occasional neuronal apoptosis), established (easily identified neuronal apoptosis) and long standing (extensive apoptosis ± endothelial swelling & calcification).

Results:

46 cases with long standing HIE: 61% had SDH, 11% had macroscopic IDH, 24% had microscopic IDH and only 4% did not show any IDH or SDH

 56 cases with established HIE: 36% had SDH, 30% had macroscopic IDH, 21% had microscopic IDH and 13% had no IDH or SDH

151 cases with early HIE: 13% had SDH, 40% had macroscopic IDH, 37% had microscopic IDH and 10% had no IDH or SDH

130 with no HIE: 4% had SDH, 31% had macroscopic IDH, 44% had microscopic IDH and 21% had no IDH or SDH

Conclusions: In our experience IDH whether microscopic or macroscopic is a very frequent finding in the post mortem examination of infants and young children. When present it is most prominent in the posterior falx and the tentorium. SDH is seen in a proportion of cases but when present there is a strong association with established or long standing hypoxic ischaemic encephalopathy. These changes are age- related

Intradural and thin film subdural haemorrhages are frequently seen in neonatal autopsies. Their presence in older infants and babies is less well documented.

Methods: We conducted an audit of autopsy reports of infants and young children over a period of 3 years (RLH) and 4 years (SCH). Intradural haemorrhage (IDH) was classified as negative, microscopic only and macroscopic.

Results:

0 to 3 months (248 cases): 26% had SDH, 30% had macroscopic IDH, 35% had microscopic IDH and 9% had no IDH or SDH

3+ to 12 months (88 cases): 7% had SDH, 28% had macroscopic IDH, 43% had microscopic IDH and 22% had no IDH or SDH

1 to 3 years (49 cases): 10% had SDH, 49% had macroscopic IDH, 16% had microscopic IDH and 25% had no IDH or SDH

Conclusions: 

In our experience microscopic and macroscopic IDH are equally frequent in infants and young children (65% 0-3m; 62% 3-12m; 65% 1-3y) but SDH is much more frequent in babies under 3 months of age where around ¼ of babies may have it. When present there is a strong association with established or long standing hypoxic ischaemic encephalopathy. We believe that the reason for this age related distribution is related to continuing maturation of the infants’ vasculature and control mechanisms.

Several types of epidermal keratinocytic nevus are recognized. We describe a previously unreported keratinocytic nevus with distinctive clinical and histopathological features.

Methods: Five patients were identified. We performed a clinical and photographic review, and obtained skin biopsy samples for histopathological examination from each patient. Genetic analysis to screen for fibroblast growth factor receptor 3 and phosphatidylinositol 3-kinase, catalytic, alpha hotspot mutations was performed on lesional skin from two patients.

Results: Five infants (2 male, 3 female) had from 1 to 11 lesions present since birth. These consisted of 1- to 7-mm hyperkeratotic papules with a rough, flat surface and a round, comma-like, rectangular, or polygonal shape. Histopathological examination showed acanthosis with broad and rectangular rete ridges, and strikingly arranged basal cells with palisaded nuclei. Genetic testing on paraffin-embedded specimens from two patients ruled out hotspot mutations in the fibroblast growth factor receptor 3 and phosphatidylinositol 3-kinase, catalytic, alpha genes.

Conclusion: We propose the name ‘‘papular epidermal nevus with ‘skyline’ basal cell layer’’ (PENS) for this newly recognized condition.

Diagnosis of Hirschsprung’s disease (HD) is generally done by rectal suction biopsies (RSB) taken at least 2cm from the pectinate line. Traditionally, at least 2 biopsies are taken, one is frozen for acetylcholinesterase (Ach) staining and the other is processed in formalin, paraffin embedded and 60 serials are cut and stained. Sections are examined for ganglion cells or nerve trunks. Negative calretinin staining has been recently described as an additional method for diagnosis of HD

Methods: RSB from 84 patients with suspicion of HD were identified between the two centres. Forty cases were diagnosed as HD based on the absence of ganglion cells ± thick nerve trunks in submucosa; when performed, positive Ach confirmed the diagnosis. All cases were stained with calretinin antibody.

Results: All normal patients showed typical calretinin staining as thin nerve fibres in lamina propria and muscularis mucosae.  38/40 biopsies on patients with HD showed complete absence of calretinin positive nerve fibres. In 2 cases there were scanty and atypical fibres in the muscularis mucosae. Previously frozen sections were negative in normal and HD cases.

Conclusions: Calretinin staining is a good coadjuvant in the diagnosis of HD and doesn’t require extra biopsies. Serial H/E sections to ascertain presence of ganglion cells is still the gold standard and a section in the middle can be taken for ICC. The method is simpler than Ach. It is important not to freeze the biopsy as a false negative will be obtained.

Background: Hydatidiform moles (HM) are characterized by an abnormal proliferating trophoblastic tissue and carry a potential of malignant transformation. Similar to other human cancers, malignant transformation in gestational trophoblastic tumours is likely a multistep process and involves multiple genetic alterations including activation of oncogenes and inactivation of tumour suppressor genes.

Material and Methods: We investigate the expression of bcl-2 and mdm-2 oncoproteins and p53, p21 and Rb tumour suppressor genes, in non-molar hydropic abortions (HA), partial HM (PHM) and complete HM (CHM). This expression was determined immunohistochemically by specific antibodies for these proteins on formalin-fixed paraffin sections of38 HA, 49 PHM and 133 CHM.

Results: Positive staining for bcl-2 and mdm-2 oncoproteins and of p21 was significantly higher in CHM and PHM than in HA (p<0.05) but there was no significant difference for the expression of these proteins between CHM and PHM. The expression of p53 and Rb was significantly higher in CHM than PHM and HA (p<0.05).

Conclusions: Altered expression of oncoproteins and tumour suppressor genes may be important in the pathogenesis of HM. A possible role of the over-expression of p53 and Rb in CHM is an attempt to modulate the excessive proliferative activity in trophoblastic cells.

Low grade fibromyxoid sarcoma [LGFMS] is a rare soft tissue sarcoma affecting young adults and typically arising in the proximal extremities and trunk Although  pediatric cases have been reported , the mediastinal location of the neoplasm is rare  We report  the case of a 12 year old boy, who presented with a anterior mediastinal tumor measuring 6 cm  Histologically the spindle cell neoplasm  was composed of alternating hypocellular and moderately cellular areas comprising  clusters and dissecting bundles of spindle cells with mild nuclear atypia and rare mitoses Characteristic features  were :a) the extensive myxoid areas and the curvilinear vasculature b) the wavy and whorling pattern in the cellular areas c) the presence of collagenous areas d) the rare collagen rosettes with peripheral epithelioid cells. Immunohistochemistry  revealed expression  of EMA , CD57, CD56 [focally] , CD99/MIC-2, bcl-2 , CD10. There was no expression of CD34, Smooth muscle actin Desmin,, Myf-4, S-100, Neurofilament GFAP Synaptophysin Myelin basic protein, ΜiTF, Calretinin, Collagen IV, c-kit , b catenin, Cytokeratins AΕ1/ΑΕ3, 8.18, 7,19,ALK-1/p-80, CD68/PG-M1. . RT-PCR performed on frozen tissue revealed the presence of the FUS/CREB3L2 fusion gene. In conclusion, The bland   and variable morphology of LGFMS , the detection of perineurial markers  make its distinction from benign mesenchymal neoplasms  and low grade sarcomas difficult  The detection of  the specific FUS/CREB3L2 or CREB3L1 fusion genes contributes significantly in the diagnosis of unusual cases  

Aim of study Clinical behaviour of pediatric adrenocortical tumors (ACT) is unpredictable. According to a diagnostic algorithm, recently proposed for adult ACT, malignant tumors invariably show a disrupted reticulin network and at least one unfavorable prognostic marker among mitotic rate (MR), necrosis, vascular invasion (Volante, 2009). The aim of this study is to test this algorithm in pediatric ACT. Materials and Methods 22 ACT (already classified according to Wieneke’ score system) were stained for reticulin. HLA-DR immunostaining was performed to identify tumors with a stromal network of dendritic cells. Results

Conclusions Malignant ACT show a disrupted reticulin network. Benign ACT are characterized by a preserved network, however in 39% of them is disrupted and may be associated with necrosis. In these cases, the prognostic categorization should combine more than one unfavorable markers in order to avoid the risk to overestimate a malignancy. The prominent dendritic network found in 60% of benign ACT with disrupted reticulin may be related to a stronger immune response compared to malignant ACT (HLA-DR + cells network in 28%).

The transcription factor Sox2 is important for development and cellular differentiation. Sox2 plays a critical role in branching of airways and epithelial cell fate determination. We aimed to investigate the role of Sox2 during differentiation. Furthermore, we investigated how it determines cell fate, and its involvement in the origin of congenital pulmonary airway malformation (CPAM).

We generated transgenic mice carrying Sox2 under the control of a doxycyclin-inducible promoter (tet-on). These transgenic mice were crossed with mice carrying the reverse tetracycline trans-activator (rtTA) under the control of the SPC promoter, which drives expression of Sox2 in airway epithelial cells upon doxycyclin administration. Timed expression of Sox2 leads to phenotypically distinct sizes of cysts in double transgenic lungs resembling CPAM. Induction of Sox2 is accompanied by the appearance of proximal cell types, shown by immunohistochemistry with p63, a basal cell marker. In contrast, withdrawal of Sox2 induction leads to loss of differentiated basal cells. Lung explant cultures show lack of branching in Sox2-induced explants. Finally, immunohistochemistry with Sox2 and p63 on a series of 20 cases of CPAM types 1 and 2 shows positive staining of both markers in the epithelial cells lining the cysts, indicating a proximal epithelial phenotype.

1-Sainte-Anne Hospital, Department of Neuropathology,PARIS,FRANCE

2- Saloul Hospital, Depatment of Radiology, SOUSSE, TUNISIA

3- Farhat-Hached Hospital, Department of Pathology, SOUSSE, TUNISIA

4-Necker-Enfants-Malades Hospital, Foetopathology Unit, PARIS, FRANCE

Objectives: Nonketotic hyperglycinemia is an autosomal recessive disorder of glycine metabolism, with a poor prognosis, in most cases. We propose to describe neuropathological data in 5 cases, and to correlate them with imaging data. Subjects and methods: We studied 5 neonates, born at term, after normal pregnancy and delivery, with normal neurological examination at birth. In the first hours of life, all neonates showed severe encephalopathy and high levels of glycine in serum and CSF. Death occurred between D5 and D15. In 3 cases, MRI examination was performed on 1,5T MR including conventional sequences, axial DWI and single voxel MRS. All cases underwent a complete autopsy with neuropathological examination.Results: MRS has shown a glycine peak confirming the abnormal accumulation of glycine in brain. Neuropathological examination showed, in all cases, a severe vacuolation of tracts and areas that complete myelination in the late 3^rd trimester of gestation and at birth (posterior limb of internal capsule, cerebellar peduncles, long tracts in the dorsal midbrain and pons). Interestingly, conventional MRI and DW-MRI showed hyperintense lesions and restricted diffusion in identical locations with more conspicuous and strikingly correlated lesions with DW-MRI. In addition, in 4 out of 5 cases, corpus callosum was extremely thin with posterior agenesis in 2 cases.Conclusion: In neonatal nonketotic hyperglycinemia, myelin vacuolation is the earliest noticeable brain injury besides, in some cases, corpus callosum malformations. The striking correlations with DW-MRI data demonstrate its crucial role  in the early detection of lesions.

Absent pulmonary valve syndrome (APVS), first described by Chevers in 1847, is a rare condition characterized by either rudimentary ridges or complete absence of pulmonic valve tissue. It is usually associated with Tetralogy of Fallot (TOF) and less commonly with an intact interventricular septum. In rare cases, APVS is linked with other vascular pathologies such as ascending aortic aneurysm (Liang et al 2010) and with Marfan’s syndrome (Childers & McCrea 1964). 22q11 is the most common gene deletion associated with this condition. However, APVS has also been associated with other genetic abnormalities such as 5q34, 8p23 and 1p22 deletion (Momma 2010). The absence of pulmonary valve tissue results in severe pulmonary regurgitation and massive dilatation of the main and branch pulmonary arteries, which compress the tracheo-bronchial tree. In addition to the compression, Rabinovitch et al (1982) reported a reduction of the number of alveoli which may explain why surgical relief of larger airway compression alone is not always effective in reversing the severe obstructive respiratory disease.    A recent antenatally diagnosed case of APVS, characterized by dilated pulmonary arteries and severe pulmonary regurgitation, was a suitable case to investigate the use of a hand-held, new form of a high definition scanner device for the rapid capture of a 3D images of parts of the heart of interest. The acquired 3D dataset and accompanied immersive visualization environment facilitated a detailed examination of the right ventricular outflow tract and the position of the absent pulmonary valve.

Case History: A female term infant, born to non-consanginous parents, unexpectedly died at 7 weeks of age. Smith-Lemli-Opitz Syndrome (SLOS) was diagnosed during life following mutational analysis.

Post Mortem Findings: External examination demonstrated growth restriction, cleft lip and palate, syndactyly of the 2nd-3rd toes and a prominent genital tubercle. Internal findings included congenital heart defects, (right ventricular hypertrophy, patent ductus arteriosus, probe patent foramen ovale), a unilobed lung and absence of fat in the adrenal glands. Biochemical analysis showed hyponatraemia. There was microcephaly and cerebellar hypoplasia. These features are well described in SLOS. Additionally, the patient demonstrated sub-valvular pulmonary artery stenosis and grade 2 pulmonary hypertension. The liver showed marked steatosis and bile duct proliferation but unusually showed no cholestasis or bile plugging. There was no extra-hepatic obstruction. These additional findings in SLOS are not well reported in the literature.

Discussion: SLOS is a rare autosomal recessive defect in the enzyme DHCR7 affecting cholesterol synthesis. There is a wide mode of presentation; whilst some of the features in this case are well recognised, others have not been widely reported. Previously a lethal form ‘type-II SLOS’ was described; however, clinically, there is a uni-modal distribution of ‘Bialer severity scores’ suggesting a single genetic entity with a wide spectrum of presentation, which is important for genetic counselling of the family. It is therefore important to recognise there may be unusual features in SLOS and to consider this diagnosis so that appropriate genetic tests may be performed.

Vitamin D is required for calcium absorption and normal bone mineralisation; it has a key role in immune regulation against infections and is believed to be involved in immunomodulation in asthma.

Methods: Retrospective review of selected post-mortem cases between 2009 and 2011. Deficient vitamin D: D2 + D3 <30nmol/L . Insufficient: <79nmol/L.

Results: Half of the children (aged between 5 days and 10 years) were vitamin D deficient and the other half (aged between 2 months and 8 years) were vitamin D insufficient.

In 3 children vitamin D deficiency was considered accountable for death; they all showed radiological and histological rickets. Two babies had cardiomyopathy. One 3.5 year old had a hypocalcaemic seizure.

In 5 children low vitamin D levels were considered a significant contributory factor to death from bronchial asthma. In 5 cases low vitamin D levels were thought to have been contributory to multi-organism infections.

Conclusions: Vitamin D deficiency (the most common form of metabolic bone disease) is preventable and treatable. Severe rickets combined with profound hypocalcaemia can cause unexpected death in babies and young children. Measuring serum vitamin D levels post-mortem may provide invaluable information on sudden unexplained death in ‘at risk’ children and in children dying from asthma. Vit D deficiency may be relevant in children with multiple infections and in babies with bone fractures. Post mortem vitamin D levels are stable and easy to measure.

Introduction:Leigh syndrome (LS) is a progressive neurological disease defined by specific neuropathological features involving brainstem and basal ganglia. It has multiple causes, resulting in a deficit in aerobic energy production.Neonatal forms of LS are very rare.

 We report the case of a neonate presenting with neurologic disturbances in which neuropathological examination  suggested   LS.

Case report: A term boy born from a primipara mother was admitted at birth for hypotonia and convulsions. Parents were consanguinous. Antenatal ultrasonography showed nuchal translucency. Karyotype was normal. Ceasarean section was performed for breech presentation and macrosomia. Apgar score was 6 and 7. The baby weight was 3970 g. The patient presented with hypotonia, seizures, macrocrania,  facial dysmorphy and hirsutism. The major frequent causes of neonatal neurologic distress were ruled out. An inborn error of metabolism was highly suspected. CNS MRI with spectroscopy couldn’t be performed. The infant died at 15^th day. Autopsy findings with neuropathologic examination revealed diffuse necrotic  lesions of the neocortex, basal ganglia, thalami and brainstem suggesting LS associated with  lesions similar to those seen  in MELAS syndrome.

Conclusion: LS encompasses a spectrum of diseases with highly variable clinical, imaging, and pathologic presentations. It manifests typically in the first two years of life saving the neonatal period, so that our cases was somewhat atypical in clinical presentation. Neuropathological examination is of great contribution in assessing the origin of unexplained neurologic symptoms.

Introduction:

Early urethral obstruction sequence consists on urethral obstruction, renal anomalies, ureterovesical dilatation, deficient abdominal wall, undescent testis and oligamnios. Our  purpose is to study the patterns of urethral obstruction, the relation between obstructive uropathy and fetal phenotype and the type of renal anomalies.

Materiel and Methods:

Retrospective study of 15 fetuses with F.O.U. Autopsy was performed with dissection of the lower urinary tract and histological study of kidneys.

Results:

Gestational age ranged between 13 and 33 weeks. The sex ratio :13/2. Prenatal findings were urinary tract abnormalities and oligamnios in 9 cases; non specified malformations in 3 cases; hydrocephalus in 1 case. Karyotype was normal in all the cases. Medical termination of pregnancy performed  in all cases. Anatomic obstruction of the urethra was found in 8 cases with 3 patterns (Atresia: 3 cases, stenosis: 3 cases, Urethral valve: 2 cases). Anatomic obstruction In 7 cases . Megacystis was in 14 cases, thin vesical wall in 12 cases, megaureters in 6 cases, bilateral hydronephrosis in 5 cases, Renal cystic changes in all cases and dysplastic changes in 11 cases.

Conclusion:

Renal changes in FOU depend on the duration of obstruction. Anatomic obstructions of the urethra should be systematically demonstrated since they are the major cause of this phenotype.

Prenatal diagnosis is compulsory indicating medical termination of pregnancy in such conditions.