Dandy-Walker Research Articles

Further Evidence of a Continuum in the Clinical Spectrum of Dominant PIEZO2-Related Disorders and Implications in Cerebellar Anomalies

Introduction: Pathogenic variants in the PIEZO family member 2 (PIEZO2) gene are known to cause Gordon syndrome (GS), Marden-Walker syndrome (MWS), and distal arthrogryposis type 5 (DA5). Out of these, MWS has a recognizable phenotype that can be discerned easily, but the distinction between GS and DA5 is less evident. Few children with pathogenic PIEZO2 variants have been reported to show posterior fossa anomalies. Methods and Results: By candidate gene targeting guided by proper clinical evaluation and neuroimaging findings, a patient with classic MWS harboring a de novo novel variant (c.8237G>A, p.W2746*) in the C-terminal region of PIEZO2 was identified. In addition, another girl with the typical clinical features of GS is also described carrying the most prevalent reported variant (c.8057G>A, p.R2686H) in PIEZO2. The brain MRI of the 2 patients showed Dandy-Walker malformation (DWM). Diffusion tensor imaging visualized anteroposterior and downward aligned thin middle cerebellar peduncle. The association of DWM with arthrogryposis in the presence of PIEZO2 variants remains quite interesting and provides more evidence that PIEZO2 plays a role in the development of hindbrain although the underlying mechanism remains unclear. Moreover, the 2 girls had distinct foot patterning in the form of shortening of the first and fifth toes. Conclusion: Phenotype analysis and a comprehensive review of the literature strongly support the previously published data and corroborate the evidence that heterozygous PIEZO2-related disorders represent a continuum with overlapping phenotypic features.

Human Cerebellar Development and Transcriptomics: Implications for Neurodevelopmental Disorders.

Developmental abnormalities of the cerebellum are among the most recognized structural brain malformations in human prenatal imaging. Yet reliable information regarding their cause in humans is sparse, and few outcome studies are available to inform prognosis. We know very little about human cerebellar development, in stark contrast to the wealth of knowledge from decades of research on cerebellar developmental biology of model organisms, especially mice. Recent studies show that multiple aspects of human cerebellar development significantly differ from mice and even rhesus macaques, a nonhuman primate. These discoveries challenge many current mouse-centric models of normal human cerebellar development and models regarding the pathogenesis of several neurodevelopmental phenotypes affecting the cerebellum, including Dandy-Walker malformation and medulloblastoma. Since we cannot model what we do not know, additional normative and pathological human developmental data are essential, and new models are needed.

Fetal Ventricular Dilation; prelude to Dandy-Walker Syndrome and Hydrocephalus: Synopsis of Two Case Reports

Accurate measurement of the 3rd and 4th ventricles is important in cases of prenatal and postnatal diagnosis of suspected cranial anomalies. Ventricular dilation occurs with excess fluid in the embryologic ventricles during brain development, we make a comparative analysis of two case reports on a 23rd-week fetus and a 10-month-old neonate. Ultrasound findings related to horns and ventricular system through transfontanelle ultrasound (excluding any > 95th error margin and < 5th percentile) can be utilized for a specific diagnosis of ventricular dilation. Hydrocephalus is defined as the accumulation of excessive CSF resulting in dilation of the cerebrospinal compartment in the calvaria; which can be acquired or congenital in origin. Hydrocephalus can also be seen due to obstructed flow, faulty absorption, and overproduction of CSF (in the subarachnoid space) by a choroid plexus papilloma. The diameter of the anterior horn of the RT and LT (hydrocephalic) lateral ventricles measured 15.3mm and 14.1mm respectively, far above the threshold for normal (control) neonates / RT and LT (anterior) lateral ventricles averaging 2.40mm and 2.51mm. These documented findings indicate the excellent agreement between fetal brain sonography in the diagnosis of fetal ventriculomegaly (anterior horn/ 10.4mm) and dilation (combined 40.8mm). Mean Head Circumference (MHC) for neonatal hydrocephalus was 44.2cm far above the normal average of 36.7cm. When we assessed the clinical benchmark of 10mm or (>19mm) for the neonate ventricle, it was far above the normal range (greater than > 95th percentile value).

Use of Frame Running for Adolescent Athletes With Movement Challenges: Study of Feasibility to Support Health and Participation.

Children and adolescents with movement challenges have lower instances of physical activity and longer time spent in sedentary behaviors compared to children with typical development. The purpose of this study was to investigate the feasibility of a sport-based youth development running program modified for accessibility using a running frame and to evaluate initial evidence for its efficacy on endurance and functional strength. We completed four 8-week seasons (2–3 times per week) in a combination of 3 different formats by season: online remote (winter and spring), in person in a community park (winter, spring, and summer), and in person in an afterschool setting (autumn). Participants included 13 athletes (average age 14.46 years, range 8–18 years, 4 females), who collectively completed 22 season blocks. Diagnoses included cerebral palsy (n = 10), arthrogryposis (n = 1), Dandy-Walker malformation (n = 1), and transverse myelitis (n = 1). In all settings, participants engaged in activities of social emotional learning, cardiovascular endurance, and muscle strengthening in a progressive manner. We found that each season format was feasible to administer with high attendance rates (76–97%) and positive qualitative feedback from athletes. In addition, promising average improvements in motor performance across a season (6 min frame running test, 170 m; timed up and go test, 8.44 s; five times sit to stand, 14.1 s; and Goal Attainment Scale, t = 65.01) were identified in the pilot data of this non-randomized cohort. Training in any of the proposed settings with an overall goal of completing a community race in a running frame is feasible and warrants further study.

A novel partial duplication in OPHN1, associated with vermis cerebellar hypoplasia, seizures and developmental delay

Pathogenic variants in the Oligophrenin 1 gene (OPHN1) cause an X-linked intellectual disability syndrome with a phenotype typically consisting of cerebellar hypoplasia, ventriculomegaly, seizures, facial dysmorphism, speech delay, and sometimes behavioral difficulties. OPHN1 is located in Xq12 and encodes a Rho-GTPase activating protein that regulates various cellular processes such as endocytosis, dendritic growth, morphology, synaptic localization, plasticity, and function. This study describes a male patient with global developmental delay, cerebellar hypoplasia, and other neuroanatomical findings suggestive of a Dandy-Walker malformation. A clinical pontocerebellar hypoplasia panel revealed a partial duplication from exon 7 to exon 15 in OPHN1 which was maternally inherited. PCR-Sanger sequencing of cDNA showed a truncating frameshift in the OPHN1 transcript.Further, transcript level analysis of OPHN1 showed a 75% reduction in the total expression in the patient in comparison to controls. Presumably, this leads to a similar decrease in the level of OPHN1 protein resulting in the observed phenotype. This is the first report of a partial duplication of exons 7–15 in OPHN1 in a patient with strabismus, speech delay, dysmorphic facial features, epilepsy, an autism-like phenotype, and developmental delay.

EP081: Dandy Walker malformation in three unrelated families with biallelic variants in CAPN15 expands the phenotypic spectrum of oculogastrointestinal neurodevelopmental disorder

Oculogastrointestinal neurodevelopmental disorder (OMIM #619318) has been described in seven previously published individuals who harbor biallelic pathogenic variants in the CAPN15 gene. Biallelic missense variants presumably lead to a more moderate phenotype of eye abnormalities and developmental delay, while biallelic loss of function (nonsense, frameshift) variants exhibit more severe phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal neurologic activity.

EP263: A pathogenic deletion at 13q32.1q33.1 presenting with bilateral sensorineural hearing loss and pigmentation anomalies, mimicking Waardenburg syndrome

13q deletion syndrome is caused by structural and functional monosomy of the long arm of chromosome 13. Individuals with partial deletions of 13q have a wide spectrum of clinical phenotypes, including mild to severe intellectual disability, growth retardation, craniofacial dysmorphism, hand and foot anomalies, brain, cardiac and renal defects. Previous reports suggest that deletions including the 13q32 band are associated with severe congenital malformations. The ZIC2 gene maps to this critical distal region at 13q32.2 and has been considered a possible candidate for brain malformations, such as holoprosencephaly and Dandy-Walker malformation. We present an individual with a 7.9 Mb deletion on chromosome 13, encompassing almost all of band q32, with a relatively mild phenotype. An 11-month-old term male was seen in the medical genetic clinic regarding concerns for possible Waardenburg Syndrome. He presented with bilateral sensorineural hearing loss at 9 months of age and was noted to have multiple hypopigmented lesions on both his feet and chest. Prenatal and post- natal course was unremarkable with normal growth and development. Physical examination revealed mild dysmorphic features such as borderline, low set and posteriorly rotated ears with folded upper helixes and a broad nasal bridge. Hypopigmented lesions consistent with leukoderma was noted over the anterior chest wall, abdominal wall and medial aspect of his right thigh. Family history was positive for a maternal cousin with similar hypopigmented lesions and maternal great, great grandmother with early premature graying of hair. There was no family history of congenital hearing loss or birth defects. A chromosomal microarray (CMA) was performed and revealed a 7.9 megabase pathogenic deletion at chromosome 13q32.1q33.1, involving 65 genes. This deletion encompasses the ZIC2 gene which is associated with holoprosencephaly. This was an unexpected finding and further imaging studies to evaluate for cardiac, renal and brain malformations have been planned. Deletions of 13q are rare and additional cases are needed to better understand the genotype-phenotype correlation. We present an atypical case of a 13q deletion syndrome associated with mild dysmorphism, bilateral sensorineural hearing loss and leukoderma. There have been suggestions that distal deletions are associated with a more severe clinical phenotype and proximal deletions causes less severe major anomalies. This case broadens the clinical spectrum of 13q deletion syndrome as hearing loss is an uncommon finding and dermatological involvement has not been previously reported. There have been one prior report indicating that the loss of Zic2 function results in impaired inner ear development in mice and may be a candidate gene that contributes to the genetics of hearing loss in humans. Additionally, although the region deleted on the long arm of chromosome 13 involves the ZIC2 gene, this patient appears to be growing and developing normally. These findings suggest regions outside of band 13q32 likely contribute to the severe congenital malformations previously associated with distal 13q deletions.

Regional brain development in fetuses with Dandy-Walker malformation: A volumetric fetal brain magnetic resonance imaging study.

Dandy-Walker malformation (DWM) is a common prenatally diagnosed cerebellar malformation, characterized by cystic dilatation of the fourth ventricle, upward rotation of the hypoplastic vermis, and posterior fossa enlargement with torcular elevation. DWM is associated with a broad spectrum of neurodevelopmental abnormalities such as cognitive, motor, and behavioral impairments, which cannot be explained solely by cerebellar malformations. Notably, the pathogenesis of these symptoms remains poorly understood. This study investigated whether fetal structural developmental abnormalities in DWM extended beyond the posterior fossa to the cerebrum even in fetuses without apparent cerebral anomalies. Post-acquisition volumetric fetal magnetic resonance imaging (MRI) analysis was performed in 12 fetuses with DWM and 14 control fetuses. Growth trajectories of the volumes of the cortical plate, subcortical parenchyma, cerebellar hemispheres, and vermis between 18 and 33 weeks of gestation were compared. The median (interquartile range) gestational ages at the time of MRI were 22.4 (19.4–24.0) and 23.9 (20.6–29.2) weeks in the DWM and control groups, respectively (p = 0.269). Eight of the 12 fetuses with DWM presented with associated cerebral anomalies, including hydrocephalus (n = 3), cerebral ventriculomegaly (n = 3), and complete (n = 2) and partial (n = 2) agenesis of the corpus callosum (ACC); 7 presented with extracerebral abnormalities. Chromosomal abnormalities were detected by microarray analysis in 4 of 11 fetuses with DWM, using amniocentesis. Volumetric analysis revealed that the cortical plate was significantly larger in fetuses with DWM than in controls (p = 0.040). Even without ACC, the subcortical parenchyma, whole cerebrum, cerebellar hemispheres, and whole brain were significantly larger in fetuses with DWM (n = 8) than in controls (p = 0.004, 0.025, 0.033, and 0.026, respectively). In conclusion, volumetric fetal MRI analysis demonstrated that the development of DWM extends throughout the brain during the fetal period, even without apparent cerebral anomalies.

The Role of Early Postoperative Intracranial Pressure Monitoring in Predicting the Outcome of Endoscopic Third Ventriculostomy Performed in Infants With Congenital Hydrocephalus: A Prospective Analysis.

IntroductionHydrocephalus is an excessive accumulation of cerebrospinal fluid (CSF) in the cavity and spaces of the brain. To date, there is no single method to accurately assess the compliance of subarachnoid spaces after endoscopic third ventriculostomy (ETV).ObjectiveTo analyze the intracranial pressure (ICP) trends in the early postoperative period in infants undergoing ETV for congenital hydrocephalus and correlate them with the final outcome.Material and methodsThis is a single-center prospective study conducted at the Department of Neurosurgery of our institute from January 2019 to February 2020. Infants presented with congenital hydrocephalus mandating ETV were included in the study. ICP was continuously monitored for the first three days after the procedure. ICP values were recorded hourly, and 24 ICP values obtained daily were averaged to obtain a daily average value (DAV).ResultsForty patients were recruited in the study. The mean age of the study population was 4.7 ± 2.8 months; 80% of the infants were <6 months of age. The male/female ratio was 5.7:1. The most common etiology was congenital aqueductal stenosis, which was observed in 18 (45%) of the patients, followed by Dandy-Walker malformation (DWM) in 11 (27.5%) of the patients. On considering a difference of >1 mmHg between the first and third postoperative day, the ETV success rate was dropped from 50% in stable trend to 11% in progressive increase trend, which was statistically significant (p = 0.044). At DAV variation of >2 mmHg in progressive increase trend, the sensitivity of stable ICP trend increased to 100% in predicting ETV success. Also, the negative predictive value (the ability of a stable trend to rule out ETV failure) reached 100%. The overall success rates of ETV in our study at one, three, and six months were 62.5%, 40%, and 35%, respectively.ConclusionA progressive increase in the ICP trend (with a difference of >2 mmHg between postoperative days 1 and 3) was the best predictor of ETV failure in our study. It was superior to any other clinical or radiological variable in our study, which was affecting the outcome.

Prenatal diagnosis of fetuses with Emanuel syndrome: Results of ultrasound examination and invasive genetic testing.

To investigate prenatal manifestations of Emanuel syndrome (ES) by retrospectively analyzing the results of prenatal diagnosis. Thirteen fetuses were collected from five hospitals, of which six were confirmed with 47,der(22)t(11;22; ES) by karyotype and chromosomal microarray analysis (CMA). Seven were diagnosed with 46,t(11;22) balanced translocations by karyotype, including one de novo mosaic 46,XX,t(11;22). In 3/7, CMA was performed but did not identify chromosomal imbalances. The results of prenatal diagnoses were reviewed, including ultrasound examinations and genetic testing. In ES fetuses, the derivative 22 was consistently inherited from the mother, while in the balanced translocation group, the t(11;22) chromosome was of paternal origin in 3/6 cases, All ES fetuses presented with multiple abnormalities by ultrasound examinations. Diaphragm hernia (3/6), Dandy-Walker complex (3/6), and kidney aplasia (3/6), were the most common ultrasound findings. Sonographic soft markers such as increased nuchal translucency, increased nuchal fold thickness appeared in 3 cases and all of these were associated with other anomalies. However, none of the ultrasound findings differentiated ES from other genetic syndromes during fetal period. In this series, in fetuses with a der(22), the derivative chromosome was consistently of maternal origin. In contrast, 46,t(11;22) balanced translocations were of maternal or paternal origin. The results contribute to the literature regarding the fetal phenotype of ES. Due to the absence of specific features distinguishing ES from other genetic syndromes, confirming the diagnosis through invasive genetic testing is necessary.

A Rare Case Report of Maple Syrup Urine Disease Associated with Dandy Walker Syndrome

A Rare Case Report of Maple Syrup Urine Disease Associated with Dandy Walker Syndrome

Craniomegaly in Neonate and Infants Requiring Neurosurgical Intervention: An Experience at Tertiary Care Center

Abstract Background The identification of neurosurgical causes of craniomegaly and early institution of therapy requires for better clinical and functional outcomes. Aims and Objectives The aim of this study was to evaluate the neurosurgical causes, managements, and outcomes of craniomegaly in neonate and infants. Materials and Methods The cases with a history of head enlargement from neonatal period were included in this study. Their causes, managements, and outcomes were recorded retrospectively during the period of January 2010 to February 2013, in neurosurgery department at SGPGIMS Lucknow, and June 2018 to June 2020, at UPUMS, Saifai, Etawah, UP, India. Results Out of 41 cases, there were 30 (73.14%) cases of hydrocephalus, 4 (9.76%) Dandy-Walker malformation, 2 (4.88%) subdural collection, 2 (4.88%) arachnoid cyst, 1 (2.44%) craniosynostosis, and 2 (4.88%) with tubercular meningitis. The age range of our cases was 18 to 178 days and the mean age was 102.54 ± 50.73. Preoperative head circumference range was 39 to 62 cm (mean: 55.27 ± 6.58cm). Majority of the cases (n = 32, 78.05%) were managed with ventriculoperitoneal shunt surgeries. Out of 41 cases, 33(80.49%) had improved outcomes, 7 (17.07%) stabilized, and mortality occurred in 1 (2.44%) case. Postoperatively, there was improvement in the head circumference (range: 39–60 cm and mean: 46.15 ± 5.83 cm) on 6 to 24 months (mean: 17.85 ± 5.18 months) of follow-up. Conclusion Hydrocephalus was the commonest neurosurgical cause of head enlargement in neonate and infants. Shunt surgery was the most common form of management of these cases. Early detection, institution of therapy, and periodic follow-up program for diagnosing and treating complications were the key to successful outcomes in these patients.

A genotype-first analysis in a cohort of Mullerian anomaly.

Müllerian anomaly (M.A.) is a group of congenital anatomic abnormalities caused by aberrations of the development process of the Müllerian duct. M.A. can either be isolated or be involved in Mendelian syndromes, such as Dandy-Walker syndrome, Holt-Oram syndrome and Bardet-Biedl syndrome, which are often associated with both uterus and kidney malformations. In this study, we applied a genotype-first approach to analyze the whole-exome sequencing data of 492 patients with M.A. Six potential pathogenic variants were found in five genes previously related to female urogenital deformities (PKD1, SON, SALL1, BMPR1B, ITGA8), which are partially overlapping with our patients' phenotypes. We further identified eight incidental findings in seven genes related to Mendelian syndromes without known association with reproductive anomalies (TEK, COL11A1, ANKRD11, LEMD3, DLG5, SPTB, BMP2), which represent potential phenotype expansions of these genes.

Dandy–Walker Malformation

Dandy–Walker Malformation (DWM) is a condition affecting the cerebellum. It consists of hypoplastic vermis, cystic enlargement of the fourth ventricle, and cystic formation near the posterior fossa. Ultrasound and magnetic resonance imaging scan are beneficial in inspecting these complications for both fetal and infantile cases. In this case series, fetal manifestations of DWM are explored through discussing maternal vitals, gestational age, clinical findings, and diagnostic imaging features (e.g., areas of encephalic enlargement and presentations of cystic dilation). It was observed that this condition is often mistaken for an arachnoid cyst, Blake’s pouch cyst, Joubert anomaly, or Arnold–Chiari malformation. It is, therefore, essential to develop a framework with sufficiently conspicuous DWM imaging features and clinical manifestations to improve diagnostic accuracy.

Dandy-Walker syndrome

А mini-review and portfolio. Every year, the number of patients with congenital defects of the nervous system increases, which, on the one hand, may be related to the improvement of postnatal neuroimaging methods, and on the other hand, to a significant increase in the influence of adverse factors on brain development in the antenatal period of a child's life. Dandy-Walker syndrome (SDU) is an abnormality in the development of the cerebellum and its surrounding cerebrospinal fluid spaces; genetically determined disease. The syndrome was first described by Americans: neurosurgeon Walter Dandy (1886 – 1946) in 1921 and neurosurgeon, neurobiologist Earl Walker (1907 – 1995) in 1944. When establishing a diagnosis, it is necessary to differentiate SDU with cerebellar hypoplasia of other etiology, retrocerebral cysts and expansion of the large cerebral cistern. A defect of the cerebellar worm, which occurs in other cases of malformations of the central nervous system, is considered a pathognomonic sign of SDU. Differential diagnosis with arachnoid cysts is carried out, which requires additional instrumental research methods. SDU usually manifests itself in childhood, but rare cases have been reported in adulthood. This is illustrated by the portfolio data. Many patients remain clinically asymptomatic for many years, while others may have various associated developmental abnormalities leading to earlier diagnosis.

Magnetic resonance imaging of Joubert syndrome associated with Dandy-Walker malformation: pathognomonic imaging.

An 8-month-old infant was referred to our institution to investigate psychomotor retardation. The clinical finding found ataxia. An MRI was indicated and performed. Sequence T1 in the axial and coronal plane (A,B) revealed a long thick superior cerebellar peduncle (Yellow arrow) and an interpeduncular fossa (White arrow), reminding the molar tooth sign (MTS). Furthermore, sequence T1 in the sagittal plane (C) showed hypoplasia of the vermis (Red arrow) and global ascension of the tentorium cerebelli (Red star). Finally, the diagnostic of Joubert syndrome associated with Dandy walker malformation was confirmed by pathognomonic imaging. The family patient was informed and received the best medical assistance. Joubert syndrome is a rare recessive ciliopathy, diagnosed by a triad in cross-sectional imaging (Scanner / MRI). (1) thick and straight superior cerebellar peduncles, (2) deep interpeduncular fossa, and (3) hypoplastic/dysplastic vermis forming the

Epidemiological and Clinical Aspects of Congenital Hydrocephalus in the Neonatal Department of Gabriel Tour&amp;#233; Teaching Hospital Bamako Mali

Objective: The aim of our work was to access the epidemiological and clinical aspects of congenital hydrocephalus in the pediatrics department of Gabriel Touré teaching Hospital Bamako. Methods: We conducted a retro and prospective study that ran from January, 1st 2018 to July, 30, 2019. All newborns of 72 hours of life or less with hydrocephalus confirmed by sonography or CT scan were enrolled in this study. Results: During the study period, 5416 patients were hospitalized in the neonatology department. Among them, 39 patients (0.72%) presented congenital hydrocephalus and congenital infectious causes accounted for 25.6%. The sex ratio (M/F) was 1.78. Mothers were housewives and not educated in 79.5% and 64.1% respectively. The parents resided outside Bamako in 61.5% of cases. Prenatal consultations were conducted in 32 patients (82%). Consanguinity between the 2 parents was present in 38.5%. The antenatal diagnosis was made in 8 patients (20.5%). Vaginal delivery was the main mode of birth (67%). The average birth weight was 2930 g (1000 to 5400 g) and the average head circumference was 37.82 cm (26 - 55 cm). In 87.2% of cases, newborns were eutrophic. The main clinical signs were bulging anterior fontanel (46.2%), sunset gaze (20.5%), prominent forehead (48.7%), reduced face (20.5%), enlarged cranial sutures (43.6%), macrocrania (25.6%). Transfontanellar ultrasound and CT scan were performed in 51.3% and 48.7% of cases respectively. Associated malformations were spina bifida in 30.8% of cases followed by Dandy Walker malformation (5.1%), and omphalocele (2.5%). The neurological signs were diminished neonatal reflexes (51.3%), hypotonia (30.8%), motor deficit (38.4%), intracranial hypertension (25.6%), seizures 10.25% and psychomotor delay (43.6%). Surgery was performed in 8 neonates (20.5%). Ventriculo-peritoneal shunt (VPB) was the main treatment. Postoperative complications were infectious (37.5%) and mechanical complications (12.5%). The postoperative mortality rate was 12.5%.The overall mortality was 13 cases (33.3%). Conclusion: The hospital frequency of congenital hydrocephalus in our environment seems low but does not reflect reality.

Dandy–Walker Malformation Presenting with Hearing Loss

Dandy–Walker malformation (DWM) is a common congenital posterior fossa anomaly, however, its association with concomitant bilateral inner ear anomalies has been rarely reported so far. We present such a case that showed characteristic imaging features of DWM along with uncommon vestibulocochlear anomalies like cochlear hypoplasia and Internal Auditory Canal atresia.

Trigeminal Neuralgia in a Case of Dandy Walker Malformation

Trigeminal Neuralgia in a Case of Dandy Walker Malformation

Very early onset schizophrenia in Dandy-Walker variant: A case report

The Sri Lanka Journal of Psychiatry (SLJP) is a peer-reviewed, open access journal published bi annually by the Sri Lanka College of Psychiatrists.The Journal publishes original papers, brief reports including case reports and commentaries relevant to psychiatry and allied sciences. The Sri Lanka Journal of Psychiatry is committed to maintaining and conforming to the editorial and ethical standards recommended by the International Committee of Medical Journal Editors.Cover“Perseverance”. These tenacious fishermen in Mannar continue their livelihood despite numerous difficulties. L. N. P. Samarasinghe, Acting Consultant Psychiatrist, Base Hospital Nikaweratiya, Sri Lanka.