Large Congenital Facial Teratoma Associated With Neurological Migration Disorder (Polymicrogyria) and Absent Corpus Callosum.

BACKGROUND: Herein, the author report a severe case of large facial mixed germ line tumor associated with neuronal migration disorder, polymicrogyria, and corpus callosum agenesis. This specific association has not been reported as yet. METHOD: A 33-year-old primiparous woman at 38th week, delivered 3820 g male baby, via Cesarian section. Postpartum profuse bleeding was noticed from a large, ulcerative, 7 cm exophytic left facial mass, which was controlled nonoperatively. The treatment included surgical excision and 560 g of large facial tumor. Histology results revealed mixed germ line tumor with grade 3, immature teratoma. RESULTS: Four months postoperatively the teratoma recurred in the buccal, tonsillar, and parapharyngeal areas. Fourteen months following the initial surgical excision the patient died from airway obstruction. CONCLUSION: Due to poor initial prognosis further treatment of the facial malignancy was not feasible. However, initial, early postnatal, excisional surgery provided a prolonged and better quality of life for the patient and family.

Novel insights into the clinical and molecular spectrum of congenital disorders of autophagy.

Autophagy is a fundamental and conserved catabolic pathway that mediates the degradation of macromolecules and organelles in lysosomes. Autophagy is particularly important to postmitotic and metabolically active cells such as neurons. The complex architecture of neurons and their long axons pose additional challenges for efficient recycling of cargo. Not surprisingly autophagy is required for normal central nervous system development and function. Several single-gene disorders of the autophagy pathway have been discovered in recent years giving rise to a novel group of inborn errors of metabolism referred to as congenital disorders of autophagy. While these disorders are heterogeneous, they share several clinical and molecular characteristics including a prominent and progressive involvement of the central nervous system leading to brain malformations, developmental delay, intellectual disability, epilepsy, movement disorders, and cognitive decline. On brain magnetic resonance imaging a predominant involvement of the corpus callosum, the corticospinal tracts and the cerebellum are noted. A storage disease phenotype is present in some diseases, underscoring both clinical and molecular overlaps to lysosomal storage diseases. This review provides an update on the clinical, imaging, and genetic spectrum of congenital disorders of autophagy and highlights the importance of this pathway for neurometabolism and childhood-onset neurological diseases.

Nonketotic Hyperglycinemia: Two Case Reports and Review.

Nonketotic hyperglycinemia (NKH) or glycine encephalopathy is an autosomal recessive disorder of glycine metabolism resulting in an excessive accumulation of glycine in all body tissues, including the central nervous system. It is caused by a biochemical defect in the glycine cleavage system and considered as a rare disorder with an estimated prevalence of 1:60,000. The neonatal form presents in the first few days of life with progressive encephalopathy, hypotonia, myoclonic jerks, hiccups, seizures, rapid progression to coma and often death due to central apnea. Surviving infants often have severe developmental delay and refractory seizures. Atypical forms of NKH present with heterogeneous and nonspecific disease course. Classical glycine encephalopathy usually carries a very poor prognosis. We describe two neonates who presented with neonatal encephalopathy, apnea, and progressive lethargy. Increased CSF glycine level along with an elevated CSF to plasma glycine ratio was suggestive of classic NKH. Burst suppression EEG and agenesis of the corpus callosum were supportive findings. Evolution of the EEG patterns and course of the disease are discussed in detail. Transient phases of clinical stabilization and normalized plasma biochemical results may not necessarily reflect the actual encephalopathic process. Serial EEGs are helpful to assess the efficacy of treatment and to modify the therapeutic approach.

Myelomeningocele with Associated Anomalies ­ Case Report and Literature Review.

Myelomeningocele is a common defect of the development of the neural tube. It is a complex congenital malformation of the central nervous system (CNS) that can be associated with other concurrent anomalies. We report on a case of lumbar myelomeningocele with concomitant CNS malformations we followed up over a period of 15 years. A concise literature review has also been performed. The current report illustrates that the myelomeningocele is a complex anomaly that is commonly associated with a variety of other CNS malformations such as hydrocephalus and Chiari malformation. It may follow chronic progressive course with exacerbation of clinical symptoms in the long term. Patients that have undergone surgical correction of this spinal defect should be closely monitored over a long period of time because of the possibility of clinical deterioration of the concomitant anomalies such as hydrocephalus, Chiari malformation and siryngomyelia.

Neurodevelopmental outcome in prenatally diagnosed isolated agenesis of the corpus callosum.

Neurodevelopmental outcome in children with agenesis of the corpus callosum (ACC) is correlated with the presence or absence of associated brain abnormalities. Indeed, neurodevelopmental outcome shows severe disabilities when the ACC is not isolated whereas in isolated forms, the neurologic development is mainly normal. Contrary to data in several published studies, the prognosis remains uncertain even in isolated forms, which may lead in France to medical termination of pregnancy. OBJECTIVE: To evaluate long-term neurodevelopmental outcome in children with prenatally diagnosed isolated ACC. DESIGN, SETTING AND PARTICIPANTS: This is a follow-up study conducted in Normandy (France). It included a cohort of 25 children born between January 1991 and June 2016, with a prenatal diagnosis of isolated ACC and who were followed for at least two years. RESULTS: The average follow-up was 8±5years. ACC was complete in 17 patients (68%), partial in 5 (20%) and hypoplastic in 3 (12%). Whereas global motor development was normal in each case, normal neurodevelopmental outcome or mild disabilities occurred in 88% children and moderate/severe neuro-disabilities were present in 12% of children. Wechsler Intelligence Scale for Children-IV evaluations and Intellectual Total Quotients were within normal range, but we observed lower scores in verbal comprehension, social judgment, executive functions. A lower score in morphosyntax was observed among 52% of children with oral language disorders. CONCLUSIONS: Neurodevelopmental outcome was favorable in most of our patients with isolated ACC, but mild learning disabilities emerged in older children. Long-term follow-up until school age is essential to provide early diagnosis and appropriate care support.

Biallelic PMS2 Mutation and Heterozygous DICER1 Mutation Presenting as Constitutional Mismatch Repair Deficiency With Corpus Callosum Agenesis: Case Report and Review of Literature.

Constitutional mismatch repair deficiency syndrome is a cancer predisposition syndrome caused by autosomal recessive biallelic (homozygous) germline mutations in the mismatch repair genes (MLH1, MSH2, MSH6, and PMS2). The clinical spectrum includes neoplastic and non-neoplastic manifestations. We present the case of a 7-year-old boy who presented with T-lymphoblastic lymphoma and glioblastoma, together with non-neoplastic manifestations including corpus callosum agenesis, arachnoid cyst, developmental venous anomaly, and hydrocephalus. Gene mutation analysis revealed pathogenic biallelic mutations of PMS2 and heterozygous DICER1 variant predicted to be pathogenic. This report is the first to allude to a possible interaction of the mismatch repair system with DICER1 to cause corpus callosum agenesis.

[A rare case of thermoregulation disorder: Shapiro syndrome]. / Shapiro-szindróma, azaz a termoregulációs zavar ritka esete.

Anomalies of the corpus callosum are the most frequent malformations of the central nervous system. The triad of spontaneous periodic hypothermia and hyperhydrosis with the agenesis of corpus callosum is described as Shapiro syndrome. Shapiro syndrome is a very rare condition and it can occur in every age group. The presence of agenesis of corpus callosum is not a strict criteria of the syndrome; the most important presenting symptom is paroxysmal hypothermia. Although the definite cause of recurrent hypothermia is unknown, dysfunction of the hypothalamus is suspected. From therapeutic aspects, only supportive therapy is available. In this report the authors present the first Shapiro syndrome case diagnosed in Hungary. The main symptoms of the 21-year-old male patient were recurrent hyperhydrosis with hypothermia resulting in severe general malaise. The skull magnetic resonance imaging demonstrated agenesis of corpus callosum. The patient was treated with clonidine resulting in significant improvement of symptoms.

Autism: cause factors, early diagnosis and therapies.

Autism spectrum disorder (ASD) is a complex neurobiological disorder characterized by neuropsychological and behavioral deficits. Cognitive impairment, lack of social skills, and stereotyped behavior are the major autistic symptoms, visible after a certain age. It is one of the fastest growing disabilities. Its current prevalence rate in the U.S. estimated by the Centers for Disease Control and Prevention is 1 in 68 births. The genetic and physiological structure of the brain is studied to determine the pathology of autism, but diagnosis of autism at an early age is challenging due to the existing phenotypic and etiological heterogeneity among ASD individuals. Volumetric and neuroimaging techniques are explored to elucidate the neuroanatomy of the ASD brain. Nuroanatomical, neurochemical, and neuroimaging biomarkers can help in the early diagnosis and treatment of ASD. This paper presents a review of the types of autism, etiologies, early detection, and treatment of ASD.

Shapiro's syndrome: Defining the clinical spectrum of the spontaneous paroxysmal hypothermia syndrome.

Shapiro Syndrome (SS) is a rare condition of spontaneous periodic hypothermia, corpus callosum agenesis (ACC) and hyperhidrosis which can occur at any age. The variant form refers to the phenotypic SS without ACC. We reported the case of SS variant on a 4-year-old boy who presented from his first year frequent episodes of hypothermia lasting 2-3 h with core rectal temperatures <35 °C. In order to understand the characteristics of this rare syndrome we searched all the cases present in literature. Fifty-two cases of SS were found in literature. Among all clinical signs, paroxysmal hypothermia seems to be the hallmark of both typical and variant SS. ACC is reported only in 40% of cases of SS. Hyperhidrosis, another hallmark of SS, was present in only 42.3% of the cases and mainly in adult onset. The presence of SS in siblings of different genders suggests an autosomal recessive inheritance model, however a gonadic mosaicism responsible for an autosomal de novo mutation cannot be ruled out. From our review of well documented cases of SS, we conclude that only the episodic and spontaneous paroxysmal hypothermia should be considered the defining hallmark of typical and variant SS. This can be important to define the clinical manifestation of SS improving the early diagnosis.

Magnetic resonance imaging findings associated with lateral cerebral ventriculomegaly in English Bulldogs.

Multiple congenital or developmental anomalies associated with the central nervous system have been reported in English Bulldogs. The purpose of this retrospective study was to identify and describe the prevalence and MRI characteristics of these anomalies and their association with presence and degree of cerebral ventriculomegaly. Magnetic resonance imaging studies of 50 English Bulldogs were evaluated. Forty-eight dogs had some degree of cerebral ventriculomegaly, 27 of which had an otherwise normal brain. Presence of lateral ventriculomegaly was not significantly associated with presence of another intracranial lesion. Appearance of the septum pellucidum was variable, ranging from intact to incomplete or completely absent. The corpus callosum was subjectively thinned in all but three dogs, two of which had normal lateral ventricles. Fusion of the rostral colliculi was not found in any dog. A persistent craniopharyngeal canal was identified in one dog. Aqueductal stenosis caused by fusion of the rostral colliculi was not identified in any dog. Findings indicated that cerebral ventriculomegaly is a common finding in English Bulldogs with or without other intracranial lesions, aqueductal stenosis caused by fusion of the rostral colliculi is unlikely to be a common etiology leading to obstructive hydrocephalus, and a large craniopharyngeal canal is a rare finding that has unknown clinical significance at this time.

Genitopatellar syndrome: a case report of a rare entity with 11 years of follow-up.

Genitopatellar syndrome is one of the syndromes described in the last decade. It is characterized by agenesis of the corpus callosum, absent or hypoplastic patellae, extremity contractures, skeletal anomalies, urogenital anomalies, and facial dysmorphic features. While writing this report, only 15 cases have been reported in the literature. The etiology, clinical features, management, and natural history of this syndrome are not yet well established. Past reports in the literature have not been able to identify the exact genetic etiology but it somewhat coincides with nail patella syndrome and short patella syndrome. We would like to introduce this terminology to the orthopedic community and highlight the clinical features of the genitopatellar syndrome. To the best of our knowledge, this is a single case report with the longest follow-up of 11 years in the literature.

Abnormal interhemispheric connectivity in neonates with D-transposition of the great arteries undergoing cardiopulmonary bypass surgery.

BACKGROUND AND PURPOSE: Neonates with severe CHD require CPB within the first days of life. White matter injury can occur before surgery, and this may impair the long-term neurodevelopmental and psychosocial outcome. The purpose of this study was to assess the microstructural development of the CC in infants with CHD before and after CPB for transposition of the great arteries. MATERIALS AND METHODS: Fifteen patients with CHD and 11 age-matched HC were recruited. We separately quantified the parallel (E1) and perpendicular (E23) diffusions, the ADC, and FA of the genu of the CC and splenium of the CC before and after surgery. RESULTS: In presurgical measures of the genu of the CC, higher E23 (P = .018), higher ADC (P = .026), and lower FA (P = .033) values were measured compared with those in HC. In the postsurgery scans, the genu of the CC had higher E23 (P = .013), higher ADC (P = .012), and lower FA (P = .033) values compared with those in HC. There was no significant difference in any DTI indices between the pre- and postsurgical groups. CONCLUSIONS: We report abnormal microstructural development in the genu of the CC of infants with d-TGA before and after CPB. High E23, high ADC, and low FA values in the genu of the CC may be explained by abnormal axonal pruning, thinner myelin sheaths, smaller axonal diameters, or more oligodendrocytes. It appears that the genu of the CC is more vulnerable than the splenium of the CC in patients with CHD and may serve as a biomarker to identify infants at highest risk for adverse neurodevelopmental outcome.

Fetal opercular cavernous angioma causing cerebral cleft: contralateral primitive vascular anomaly and subicular dysgenesis.

We describe a 22-week female fetus after pregnancy was terminated because of fetal magnetic resonance imaging showing a large left cerebral hemispheric cleft suggestive of porencephaly or schizencephaly. Postmortem examination revealed a large cavernous angioma of the left opercular region with evidence of previous hemorrhage and extensive cerebral infarction. In the right hemisphere, another vascular malformation within the frontal germinal matrix consisted of an aggregate of primitive vessels not yet canalized. Selective dysgenesis of the right subiculum also was demonstrated. This case illustrates not only a severe encephaloclastic effect of cavernous angioma in fetal brain but also the importance of fetal autopsy to help correlate and explain fetal neuroimaging. Potential future prenatal treatment of fetal angiomata requires precise in utero diagnosis.