Knockout mice with pituitary malformations help identify human cases of hypopituitarism.

BACKGROUND: Congenital hypopituitarism (CH) and its associated syndromes, septo-optic dysplasia (SOD) and holoprosencephaly (HPE), are midline defects that cause significant morbidity for affected people. Variants in 67 genes are associated with CH, but a vast majority of CH cases lack a genetic diagnosis. Whole exome and whole genome sequencing of CH patients identifies sequence variants in genes known to cause CH, and in new candidate genes, but many of these are variants of uncertain significance (VUS). METHODS: The International Mouse Phenotyping Consortium (IMPC) is an effort to establish gene function by knocking-out all genes in the mouse genome and generating corresponding phenotype data. We used mouse embryonic imaging data generated by the Deciphering Mechanisms of Developmental Disorders (DMDD) project to screen 209 embryonic lethal and sub-viable knockout mouse lines for pituitary malformations. RESULTS: Of the 209 knockout mouse lines, we identified 51 that have embryonic pituitary malformations. These genes not only represent new candidates for CH, but also reveal new molecular pathways not previously associated with pituitary organogenesis. We used this list of candidate genes to mine whole exome sequencing data of a cohort of patients with CH, and we identified variants in two unrelated cases for two genes, MORC2 and SETD5, with CH and other syndromic features. CONCLUSIONS: The screening and analysis of IMPC phenotyping data provide proof-of-principle that recessive lethal mouse mutants generated by the knockout mouse project are an excellent source of candidate genes for congenital hypopituitarism in children.

Co-occurrence of Attention-Deficit/Hyperactivity Disorder and Septo-Optic Dysplasia: A Neurodevelopmental Case Report.

Septo-optic dysplasia (SOD) is a rare congenital disorder characterized by optic nerve hypoplasia, brain midline structure anomalies, and hypothalamic-pituitary axis hypoplasia. This case report aims to highlight the association between SOD and neurodevelopmental disorders, focusing on attention-deficit/hyperactivity disorder (ADHD) in addition to the well-established link with autism spectrum disorder (ASD). A six-year-old male diagnosed with SOD presented with behavioral concerns, including attention and impulse control issues. A comprehensive psychological evaluation confirmed the diagnosis of ADHD and ruled out ASD. Ophthalmological assessments were integral to understanding the patient's condition. This case underscores the importance of recognizing neurodevelopmental disorders in individuals with SOD, with a particular focus on the less common association with ADHD. The co-occurrence of these conditions underscores the complexity of neurodevelopmental disorders and the need for comprehensive evaluation and management. Collaboration between ophthalmologists and mental health specialists is crucial for addressing the diverse needs of these patients. Early identification and intervention for ADHD are essential for optimal developmental outcomes. This case underscores the necessity for further research to elucidate the relationship between SOD and ADHD, emphasizing the importance of holistic patient care and interdisciplinary collaboration in managing individuals with SOD spectrum conditions.

Segmental Agenesis of the Corpus Callosum With Pituitary Hypoplasia.

We report a 3-year-old male with findings of segmental agenesis of the corpus callosum, pituitary hypoplasia, and Chiari I malformation. The patient was born at 33 weeks and spent five weeks in the NICU for hypoglycemia, hypotension, and dyspnea. In infancy, the patient passed an adrenocorticotropic hormone stimulation test, while cortisol, growth hormone, and insulin-like growth factor levels were within reference range. Following height and weight percentile regression the patient underwent arginine and clonidine stimulation testing at 3 years of age, prompting pituitary evaluation via MRI. The results provided exemplary neuroimaging of segmental callosal agenesis, in which the genu and splenium form despite the absence of the callosal body. This finding adds support to a newer theory of embryological callosal development where progression does not occur linearly in the rosto-caudal direction.

Rare encounter: Adult-onset temporal lobe schizencephaly with septo-optic dysplasia - a case report on comprehensive diagnosis and management.

This case report presents a 21-year-old male with recurrent seizures attributed to isolated temporal lobe closed-lip schizencephaly coexisting with septo-optic dysplasia. Despite adult-onset seizures, the patient lacked motor deficits, maintaining normal developmental milestones. Comprehensive diagnostic modalities, including MRI revealing temporal lobe atrophy and associated abnormalities, contributed to the unique identification of schizencephaly. The classic triad of septo-optic dysplasia further complicated the clinical spectrum. Financial limitations influenced the predominantly conservative management, highlighting healthcare challenges. This case enhances our understanding of the rare congenital disorder, emphasizing the importance of tailored diagnostics and management strategies for diverse presentations of schizencephaly, particularly in the context of associated congenital anomalies.

Stress-Induced Oculogyric Crisis in Septo-Optic Dysplasia: Case Report.

Introduction: Oculogyric crisis (OGC) is a dystonic movement disorder of varying durations that manifests as bilateral paroxysmal upward eye deviation accompanied by involuntary blinking, tongue protrusion, and autonomic symptoms. Separately, septo-optic dysplasia (SOD) is a congenital disorder involving hypoplasia of the optic nerve as well as hypothalamic and pituitary abnormalities. In the presented case, we report a case of OGC in the setting of SOD with proposed pathogenesis. Case Presentation: A 27-year-old female presented with a history of SOD (optic nerve hypoplasia and hypopituitarism) with acute, recurrent, painless, bilateral, intermittent, simultaneous tonic conjugate upward eye deviation (i.e., OGC) and dystonic body posturing. She experienced her first episode upon meeting her biological sister for the first time at a loud, crowded public restaurant with continued episodes of OGC increasing in frequency and duration over the subsequent months. She later responded well to treatment with carbidopa/levodopa. Conclusion: Based on our current understanding of OGC, we hypothesize that acute stressful life events in the setting of prior hypothalamic-pituitary axis dysfunction secondary to SOD could lower the threshold for developing OGC. Although most cases of OGC are idiopathic, various etiologies including medications, stress, and hormonal imbalance have been postulated as possible pathogenic mechanisms. We describe a case of SOD with OGC, and based upon our review of the English language ophthalmic literature, we believe that our case is novel.

Arousal, Gray's theory of anxiety, and the etiology of psychopathy.

This paper focuses on Jeffrey Gray's theory of anxiety from the perspective of Fowles' (1980) application of his work to theories of arousal, psychophysiology, and the etiology of psychopathy. Although highly influential, the concept of general arousal failed to find support in terms of between-individuals assessment with multiple physiological measures. Gray's constructs of a behavioral inhibition system (BIS) that mediates anxiety, a behavioral approach or activation system (BAS) that energizes behavior to approach rewards, and a nonspecific arousal system that energizes behavior captured aspects of arousal. Fowles (1980) proposed that the BIS elicits electrodermal activity in response to threats, the BAS increases heart rate in response to reward incentive cues, and psychopathy is associated with a weak BIS. The paper reviews Gray's impact on future research on these topics, including early proposals relevant to the National Institute of Mental Health's Research Domain Criteria. Finally, the paper summarizes the evolution of theories of the etiology of psychopathy since 1980, noting ways in which aspects of Gray's theory are still seen in psychopathy research. Patrick's triarchic model has emerged as a major theory of psychopathy. Beauchaine's trait impulsivity theory of Attention Deficit Hyperactivity Disorder also is relevant.

Septo-Optic Dysplasia: A Case Series of 33 Patients.

The objective of this study was to record the clinical, neuro-radiological, and systemic features of patients with septo-optic dysplasia (SOD). A retrospective review of patients was conducted to identify patients with features consistent with SOD over a 6-year period, including optic nerve hypoplasia with agenesis of midline structures, along with an absent septum pellucidum and/or agenesis of the corpus callosum. Thirty-three patients were identified. The male to female ratio was 2:1, while the median age at diagnosis was 5 years (interquartile range = 10 years, range = 0-44 years). Optic nerve hypoplasia (ONH) was bilateral in 81.81% of cases (n = 27) and unilateral in 18.18% of cases (n = 6), with three cases in each eye. Developmental delay was documented in 24.2% (n = 8). The most frequent magnetic resonance imaging features that were consistent with SOD included: isolated absent septum pellucidum reported in 51.51% (n = 17); isolated corpus callosum agenesis in 33.33% (n = 11); and both absent septum pellucidum and corpus callosum agenesis in 15.15% (n = 5). Pituitary gland abnormalities, including pituitary hypoplasia in 9% (n = 3) or hypoplasia of pituitary infundibulum in 6% (n = 2) were less common. Pituitary hormonal abnormalities were present in 50% of the 10 tested patients (n = 5). Although bilateral ONH is more frequent, hypoplasia of just one optic nerve could be a presenting feature of SOD. Therefore, additional neuro-imaging is important for a diagnosis in cases of unilateral and bilateral ONH and a multidisciplinary approach is beneficial.

Displasia septo-óptica (síndrome de De Morsier) con hipopituitarismo y sus múltiples complicaciones: reporte de un caso y revisión de literatura

Presentamos el caso de una paciente con displasia septo-óptica (SOD), también conocida como síndrome de De Morsier, un desorden congénito raro. Se caracteriza por una combinación de alteraciones: hipoplasia del nervio óptico, disfunción hipofisaria y anormalidades de la línea media. Presentamos el caso de una paciente de 37 años con síndrome de De Morsier que consulta por infertilidad. Asocia hipopituitarismo, con déficit de hormona de crecimiento e hipogonadismo hipogonadotrófico, diagnosticada a los 11 años, en contexto de hipocrecimiento e impuberismo. También presenta complicaciones asociadas a estos déficits, como infertilidad, síndrome metabólico y compromiso óseo. Un diagnóstico y tratamiento temprano puede prevenir la morbimortalidad asociada a este síndrome, pero no así la infertilidad. Sin embargo, es posible lograr el embarazo mediante inducción de la ovulación.

The study presents the case of a patient with septo-optic dysplasia (SOD), also known as de Morsier syndrome, which is a rare congenital disorder. It is characterized by a combination of abnormalities, including optic nerve hypoplasia, pituitary dysfunction, and midline abnormalities. We present the case of a 37-year-old female patient with De Morsier syndrome, who seeks medical attention due to infertility. She presents with hypopituitarism, characterized by growth hormone deficiency and hypogonadotropic hypogonadism, diagnosed at the age of 11 in the context of short stature and delayed puberty. The patient also exhibits complications associated with these deficits, such as infertility, metabolic syndrome, and skeletal compromise. Early diagnosis and treatment can prevent morbidity and mortality associated with this syndrome, but unfortunately, infertility remains unaffected. Nevertheless, achieving pregnancy is possible through ovulation induction.

A síndrome de De Morsier, é uma doença congênita rara, caracterizada por uma combinação de alterações: hipoplasia do nervo óptico, disfunção hipofisária e anomalias da linha média. Apresentamos o caso de uma paciente de 37 anos com displasia septo-óptica (SOD), também conhecida como síndrome de De Morsier que consultou por infertilidade. Associado à SOD detectou-se hipopituitarismo, com deficiência de hormônio do crescimento e hipogonadismo hipogonadotrófico diagnosticado aos 11 anos de idade em um contexto de hipocrescimento e impuberdade. Foram observadas também complicações associadas a esses déficits como infertilidade, síndrome metabólica e envolvimento ósseo. O diagnóstico e tratamento precoces podem prevenir a morbimortalidade associada a esta síndrome, mas não a infertilidade. No entanto, a gravidez é possível através da indução da ovulação.

Resultado a largo plazo de una serie de fetos con agenesia aislada del septum pellucidum / Long-term postnatal outcome of fetuses with isolated agenesis of the septum pellucidum

Objetivo: Reportar el resultado a largo plazo de una serie de fetos con agenesia del septum pellucidum aislada (ASP), con medición de su quiasma óptico mediante neurosonografía fetal (NSG). Método: Se incluyeron todas las pacientes con ASP y NSG evaluadas desde el año 2008 a la fecha y con seguimiento hasta su edad escolar. En todos los casos se consignaron los datos clínicos de NSG y de resonancia magnética (RM), cuando esta se realizó. Se entrevistó telefónicamente a los padres. Resultados: Nueve pacientes cumplieron los criterios: cuatro con displasia septo-óptica (DSO) (rango de seguimiento: 5-14 años) y cinco sin DSO (rango de seguimiento: 7-10 años). Un décimo caso se excluyó por tener solo 6 meses de seguimiento. Ninguna de las ASP tuvo otra anomalía detectada en su seguimiento. Ninguno de los casos con DSO tuvo alteración del tamaño de su quiasma óptico en la NSG ni anormalidad en la vía óptica en la RM. Conclusiones: En nuestra población, el riesgo residual de DSO frente a ASP es del 44,4%. En el seguimiento, nuestra definición de ASP por NSG no tuvo falsos negativos con relación a otras anomalías de aparición posnatal, a excepción de la DSO.

Objective: To report the long-term outcome of a series of fetuses with isolated septum pellucidum agenesis (ASP) with measurement of their optic chiasm by fetal neurosonography (NSG). Method: All patients with ASP and NSG evaluated from 2008 to date and with follow-up until their school age were included. In all cases, clinical, NSG and magnetic resonance imaging (MRI) data were recorded. Parents were interviewed by telephone. Results: Nine patients met the criteria: four with septo-optic dysplasia (SOD) (follow-up range: 5-14 years) and five without SOD (follow-up range: 7-10 years). A tenth case was excluded because only 6 months of follow-up. None of the ASP cases had another anomaly detected in their follow-up. None of the cases with DSO had anomaly of the size of their optic chiasm on NSG or abnormality in the optical pathway in the MRI. Conclusions: In our population, the residual risk of DSO versus ASP is 44.4%. At follow-up, our NSG definition of ASP had no false negatives in relation to other postnatal-onset anomalies, except for SOD.

Metroplastia cervical histeroscópica en útero septo completo, septo cervical y tabique vaginal. Análisis de resultados clínicos y reproductivos en serie de casos de 2011 a 2021 / Hysteroscopic cervical metroplasty in complete uterus septum, cervical septum and vaginal septum: Analysis of clinical and reproductive outcomes in a series of cases from 2011 to 2021

Antecedentes: El útero septo con septo cervical y tabique vaginal es una entidad poco frecuente únicamente descrita en clasificaciones que recogen malformaciones müllerianas complejas como son las clasificaciones de VCUAM (2005), de ESHRE/ESGE (2013) y de ASRM (2021). El objetivo de nuestro trabajo es describir los resultados en nuestras pacientes de la metroplastia cervical histeroscópica según técnica de Vercellini. Material y método: Se trata de un estudio observacional de cohortes retrospectivo con una duración de 10años. Se incluyeron solo pacientes con diagnóstico de útero septo completo, septo cervical y tabique vaginal con indicación de metroplastia cervical según técnica de Vercellini entre los años 2011 y 2021. Resultados: Se analizaron los resultados de 5 pacientes con indicación de la técnica. Analizando nuestro resultado destacamos un recién nacido vivo a término tras la realización de la técnica, la cual mantuvo seguimiento en consulta de prematuridad sin modificaciones cervicales consecuencia de la resección del tabique cervical. Conclusión: Existe muy poca evidencia disponible en cuanto al tratamiento del útero septo completo con septo cervical y tabique vaginal, debido a la escasa prevalencia del mismo y a la heterogeneidad del diagnóstico. Analizando los resultados obtenidos consideramos la intervención de Vercellini eficaz para eliminar el septo, la cual no parece asociarse a complicaciones mayores ni menores. En base a la evidencia existente, podría ser útil para mejorar el pronóstico reproductivo de las pacientes que presentan este tipo de malformación, individualizando la necesidad de un segundo retoque histeroscópico.(AU)

Background: The septum uterus with cervical septum and vaginal septum is a rare entity only described in classifications that include complex Müllerian malformations such as the VCUAM (2005), ESHRE/ESGE (2013) and ASRM (2021) classifications. The objective of our work is to describe the results of hysteroscopic cervical metroplasty according to the Vercellini technique in our patients. Material and method: This is a retrospective observational cohort study with a duration of 10years. Only patients with a diagnosis of a complete septum uterus, cervical septum, and vaginal septum with indication of cervical metroplasty according to the Vercellini technique between 2011 and 2021 were included. Results: The results of five patients with indication of the technique were analyzed. Analyzing our result, we highlight a live newborn at term after performing the technique, which was followed up in the prematurity clinic without cervical modifications because of the resection of the cervical septum. Conclusion: There is very little evidence available regarding the treatment of the uterus complete septum with cervical septum and vaginal septum due to its low prevalence and the heterogeneity of the diagnosis. Analyzing the results obtained, we consider the Vercellini intervention to be effective in removing the septum, which does not seem to be associated with major or minor complications. Based on the existing evidence, it could be useful to improve the reproductive prognosis of patients with this type of malformation; individualizing the need for a second hysteroscopic touch-up.(AU)

Hyaluronic Acid Conjugated with 17ß-Estradiol Effectively Alleviates Estropause-Induced Cognitive Deficits in Rats.

Women are at a higher risk of cognitive impairments and Alzheimer's disease (AD), particularly after the menopause, when the estrous cycle becomes irregular and diminishes. Numerous studies have shown that estrogen deficiency, especially estradiol (E2) deficiency, plays a key role in this phenomenon. Recently, a novel polymeric drug, hyaluronic acid-17ß-estradiol conjugate (HA-E2), has been introduced for the delivery of E2 to brain tissues. Studies have indicated that HA-E2 crosses the blood-brain barrier (BBB) and facilitates a prolonged E2 release profile while lowering the risk of estrogen-supplement-related side effects. In this study, we used ovariohysterectomy (OHE) rats, a postmenopausal cognitive deficit model, to explore the effect of a 2-week HA-E2 treatment (210 ng/kg body weight, twice a week) on the cholinergic septo-hippocampal innervation system, synaptic transmission in hippocampal pyramidal neurons and cognitive improvements. Our study revealed an 11% rise in choline acetyltransferase (ChAT) expression in both the medial septal nucleus (MS nucleus) and the hippocampus, along with a 14-18% increase in dendritic spine density in hippocampal pyramidal neurons, following HA-E2 treatment in OHE rats. These enhancements prompted the recovery of cognitive functions such as spatial learning and memory. These findings suggest that HA-E2 may prevent and improve estrogen-deficiency-induced cognitive impairment and AD.

Partial ectopic posterior pituitary: A rare imaging entity with literature review.

Abnormal development of the posterior pituitary gland can lead to an ectopic location of the neurohypophysis, commonly seen at the median eminence of the hypothalamus or along the infundibular stalk. A partial ectopic posterior pituitary (PEPP) is a very rare variant of the ectopic posterior pituitary, defined as the presence of a double bright spot of neurohypophysis seen in both orthotopic and ectopic locations. We report a two-year-old male toddler with bilateral optic nerve hypoplasia and severe visual impairment who presented to the endocrine outpatient clinic for hypopituitarism evaluation. Magnetic resonance imaging (MRI) of the brain revealed a hypoplastic pituitary gland and infundibulum with a double bright spot of neurohypophysis in the expected normal location and along the median eminence. Severe hypoplasia of both optic nerves and the optic chiasm was also seen. Septum pellucidum was present with no evidence of other brain malformations. The findings are in the septo-optic dysplasia spectrum associated with hypothalamic-pituitary dysfunction and a very rare entity called PEPP. To our knowledge, only a handful of reported cases of this rare entity exist in the literature.

Ultrasound Assessment of the Fetal Optic Chiasm.

This article reviews the literature on different methods of prenatal ultrasound visualization of the optic chiasm (OC) and its applications. Prenatal imaging of the OC is feasible from 19 to 37 weeks of gestation. Evaluation of the OC has been shown crucial in differentiating isolated agenesis of the septum pellucidum from septo-optic dysplasia. Multiple methods can be applied for imaging of the OC, including three-dimensional and two-dimensional ultrasounds in different views, as well as color Doppler. According to the literature, both transabdominal and transvaginal routes produce equally acceptable images. OC visualization might be challenging but can be achieved by developing a standard scanning protocol and raising awareness.

Central Diabetes Insipidus in Children as a Diagnostic Challenge.

Central diabetes insipidus (CDI) is a disorder in the pediatric population resulting from antidiuretic hormone deficiency. The excessive production of dilute urine characterizes it and manifests with polyuria, nocturia, and polydipsia. The diagnostics of CDI is often challenging, especially concerning the underlying condition of the disease. This article highlights the diverse clinical presentation of children with CDI and diagnostic difficulties among patients with polyuria and polydipsia. The article also reviews the etiology, symptoms, diagnostic workup, and management of CDI. We present 4 pediatric patients (aged 3-13.5 years) diagnosed with CDI of different etiology: 1 due to septo-optic dysplasia/optic nerve hypoplasia and 3 due to acquired processes such as Langerhans cell histiocytosis and germ cell tumor in 2 patients. Central diabetes insipidus was the first manifestation of a tumor or granuloma in all presented patients with acquired pathology. The patients sometimes need long-term follow-up to establish the proper final diagnosis.

How to ablate the septo-pulmonary bundle: a case-based review of percutaneous ablation strategies to achieve roof line block.

Electrical conduction through cardiac muscle fibres separated from the main myocardial wall by layers of interposed adipose tissue are notoriously difficult to target by endocardial ablation alone. They are a recognised important cause for procedural failure due to the difficulties of delivering sufficient energy via the endocardial radiofrequency catheter to reach the outer epicardial layer without risking adverse events of the otherwise thin walled atria. Left atrial ablations for atrial fibrillation (AF) and tachycardia are commonly affected by the presence of several epicardial structures, with the septo-pulmonary bundle (SPB), Bachmann's bundle, and the ligament of Marshall all posing substantial challenges for endocardial procedures. Delivery of a transmural lesion set is essential for sustained pulmonary vein isolation and for conduction block across linear atrial lines which in turn has been described to translate into a reduced AF/atrial tachycardia recurrence rate. To overcome the limitations of endocardial-only approaches, surgical ablation techniques for epicardial or combined hybrid endo-epicardial ablations have been described to successfully target these connections. Yet, these techniques confer an increase in procedure complexity, duration, cost, and morbidity. Alternatively, coronary venous system ethanol ablation has been successfully employed by sub-selecting the vein of Marshall to facilitate mitral isthmus line block, although this approach is naturally limited to this area by the coronary venous anatomy. Increased awareness of the pathophysiological relevance of these epicardial structures and their intracardiac conduction patterns in the era of high-resolution 3D electro-anatomical mapping technology has allowed greater understanding of their contribution to the persistence of AF as well as failure to achieve transmural block by traditional ablation approaches. This might translate into novel catheter ablation strategies with procedural success rates comparable to surgical 'cut-and-sew' techniques. This review aims to give an overview of percutaneous catheter ablation strategies to target the SPB, an important cause of failed block across the roof line and isolation of the left atrial posterior wall and/or the pulmonary veins. Existing and investigational technologies will be discussed and an outlook of future approaches provided.

Neurodevelopmental impairments in children with septo-optic dysplasia spectrum conditions: a systematic review.

BACKGROUND: Septo-optic dysplasia (SOD) is a rare condition diagnosed in children with two or more of the following: hypopituitarism, midline brain abnormalities, and optic nerve hypoplasia. Children with SOD experience varied visual impairment and endocrine dysfunction. Autistic-like behaviours have been reported; however, their nature and prevalence remain to be fully understood. The present systematic review aimed to explore the type and prevalence of neurodevelopmental impairments in children with SOD spectrum conditions. METHODS: The search was conducted in PubMed, EMBASE, and PsycInfo. Hand-searching reference lists of included studies was conducted. All peer-reviewed, observational studies assessing behavioural and cognitive impairments or autism spectrum disorder (ASD) symptoms in children (< 18 years) with SOD, optic nerve hypoplasia, and SOD-plus were included. Studies were excluded if they did not report standardised measures of neurodevelopmental impairments or ASD outcomes. RESULTS: From 2132 screened articles, 20 articles reporting data from a total of 479 children were included in prevalence estimates. Of 14 studies assessing cognitive-developmental outcomes, 175 of 336 (52%) children presented with intellectual disability or developmental delay. A diagnosis of ASD or clinical level of symptoms was observed in 65 of 187 (35%) children across five studies. Only five studies assessed for dysfunction across behavioural, emotional, or social domains and reported impairments in 88 of 184 (48%) of children assessed. LIMITATIONS: Importantly, high heterogeneity among the samples in relation to their neuroanatomical, endocrine, and optic nerve involvement meant that it was not possible to statistically assess the relative contribution of these confounding factors to the specific neurodevelopmental phenotype. This was further limited by the variation in study designs and behavioural assessments used across the included studies, which may have increased the risk of information bias. CONCLUSIONS: This systematic review suggests that the prevalence of neurodevelopmental impairments in children within the SOD spectrum may be high. Clinicians should therefore consider including formal assessments of ASD symptoms and neurodevelopmental impairments alongside routine care. There is, additionally, a need for further research to define and validate a standardised battery of tools that accurately identify neurodevelopmental impairments in SOD spectrum conditions, and for research to identify the likely causal mechanisms.

Neuroimaging Features in Children with Optic Nerve Hypoplasia and Septo-Optic-Pituitary Dysplasia.

BACKGROUND: Optic nerve hypoplasia (ONH) and septo-optic-pituitary dysplasia (SOD) are common causes of congenital visual impairment. Our primary aim was to investigate the prevalence of abnormal neuroimaging features in patients with these disorders in Manitoba, Canada, and compare them with published reports. METHODS: A retrospective neuroimaging review was performed in patients resident in Manitoba with ONH/SOD. RESULTS: There were 128 patients (M = 70) with ONH/SOD who had neuroimaging. Their mean age (SD) at the end of the study was 13.2 (7.5) years. Males were significantly more likely to have bilateral ONH and a small optic chiasm size, while females were more likely to have a left ONH and a small left optic chiasm size on neuroimaging (p = 0.049). ONH and small optic chiasm size were seen in most patients on neuroimaging. Absent septum pellucidum was noted in 40%, small pituitary gland size in 28%, neuronal migration disorders (NMD) in 20% (>1 type and bilateral in 13 cases), corpus callosum abnormalities were present in 9%, while olfactory bulbs-tracts and olfactory sulci were absent in 8.6% of cases. Unilateral ONH was not significantly associated with other structural brain abnormalities, while NMD were significantly associated with other midline brain abnormalities including a symmetrically small optic chiasm size. CONCLUSION: The prevalence of structural neuroimaging abnormalities in our cohort with ONH/SOD was generally in the same range reported in other studies with corpus callosum abnormalities being relatively less common in our study. Bilateral NMD were relatively common among patients with NMD. The association between sex and ONH laterality requires further study.

The clinical aspects of septo-optic dysplasia: A narrative review with illustrative case report.

INTRODUCTION AND IMPORTANCE: Septo-optic dysplasia (SOD) is a rare congenital disorder characterized by abnormal development of the optic nerve, pituitary gland, hypothalamus, and midline brain structures, with heterogeneous presentation among cases. CASE PRESENTATION: We report a seven-month-old male infant presented with persistent vomiting and delayed developmental milestones. He had dysmorphic facial features, bilateral esotropia, a head circumference of 50 cm, and scoliosis. His muscle tone was high (clasp-knife spasticity) and his deep tendon reflexes were brisk in the four limbs. Clinical evaluation and brain MRI confirmed the diagnosis of SOD, for which, he was subjected for multidisciplinary evaluation. Genetic testing revealed an autosomal dominant TUBB gene mutation. On follow-up, at the age of three years, he presented with recurrent focal motor and generalized seizures, which were controlled with levetiracetam. CLINICAL DISCUSSION: The ophthalmic manifestations of SOD include optic nerve hypoplasia, which can lead to visual impairments such as nystagmus, strabismus, and reduced visual acuity. Midline brain anomalies involve structures like the corpus callosum and septum pellucidum, and can result in cognitive and neurological deficits. Hypothalamic-pituitary axis abnormalities can cause endocrine dysfunction and growth abnormalities. The clinical heterogeneity of SOD is attributed to variable phenotypic penetration and genetic mutations. Environmental risk factors may also contribute to the development of the syndrome. CONCLUSION: SOD is a complex disorder with diverse clinical manifestations. Early diagnosis and multidisciplinary management are crucial for optimizing patient outcomes. Further research is needed to understand the underlying genetic and environmental factors involved in SOD and to develop targeted treatments.

Septo-optic dysplasia PLUS syndrome in a 23 years old patient: A case report.

Septo-optic dysplasia (SOD) is a rare malformation defined by septum pellucidum abnormalities and hypoplasia of the optic nerves and chiasm. It can be associated with cortical development malformations such as schizencephaly, which is then called septo-optic dysplasia plus. It usually manifests at birth, although it may not be diagnosed until childhood, or rarely, adolescence. We report the case of a 23 years old patient, with a history of epilepsy since early childhood never labeled, which was diagnosed with SOD-PLUS with brain MRI in our department.