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.

Displasia septo-óptica: hallazgos imagenológicos y revisión de tema / Septo-Optic Dysplasia: Imaging Findings and Review of the Literature

La displasia septo-óptica, también conocida como síndrome de De Morsier, es una enfermedad congénita que consiste en una combinación variable de defectos en su presentación clínica e imagenológica. Todos los pacientes con hipoplasia del nervio óptico deben ser estudiados imagenológicamente, en especial con resonancia magnética, con el objetivo de detectar anomalías en el desarrollo de las estructuras de la línea media del sistema nervioso central. Se realizó una revisión de la literatura y una evaluación retrospectiva de los pacientes de nuestra institución, con el fin de ilustrar los principales hallazgos neurorradiológicos de este síndrome.

Septo-optic dysplasia, also known as De-Morsier syndrome, is a congenital disease that presents a variable combination of defects in its clinical and imaging presentation. All patients with optic nerve hypoplasia must be studied by imaging, especially with magnetic resonance imaging, with the aim of detecting abnormalities in the development of the midline structures of the central nervous system. A review of the literature and subsequently a retrospective evaluation of the patients of our institution was carried out in order to illustrate the main neuroradiological findings of this syndrome.

Combined pituitary hormone deficiency caused by PROP1 mutations: update 20 years post-discovery

ABSTRACT The first description of patients with combined pituitary hormone deficiencies (CPHD) caused by PROP1 mutations was made 20 years ago. Here we updated the clinical and genetic characteristics of patients with PROP1 mutations and summarized the phenotypes of 14 patients with 7 different pathogenic PROP1 mutations followed at the Hospital das Clínicas of the University of Sao Paulo. In addition to deficiencies in GH, TSH, PRL and gonadotropins some patients develop late ACTH deficiency. Therefore, patients with PROP1 mutations require permanent surveillance. On magnetic resonance imaging, the pituitary stalk is normal, and the posterior lobe is in the normal position. The anterior lobe in patients with PROP1 mutations is usually hypoplastic but may be normal or even enlarged. Bi-allelic PROP1 mutations are currently the most frequently recognized genetic cause of CPHD worldwide. PROP1 defects occur more frequently among offspring of consanguineous parents and familial cases, but they also occur in sporadic cases, especially in countries in which the prevalence of PROP1 mutations is relatively high. We classified all reported PROP1 variants described to date according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines: 29 were pathogenic, 2 were likely pathogenic, and 2 were of unknown significance. An expansion of the phenotype of patients with PROP1 mutations was observed since the first description 20 years ago: variable anterior pituitary size, different pathogenic mutations, and late development of ACTH deficiency. PROP1 mutations are the most common cause of autosomal recessive CPHD with a topic posterior pituitary lobe. Arch Endocrinol Metab. 2019;63(2):167-74

Knowledge and Practical Attitudes of Surgeons-Dentists of Bamako District Facing the Septum Syndrome

Objective: To determine the knowledge and attitude of dental surgeons in Bamako regarding the management of septal syndromes. Material and Methods: It was a crosssectional and descriptive study conducted in the Bamako District, Mali. The following variables were collected: sociodemographic, training, knowledge of septal syndrome, therapeutic decisions and treatment. The data was collected from a survey sheet and processed by Epi-info Software version 3.5.3 and by the language R. Results: A total of 67 professionals participated in this study, of which 88.1% were men. Seventy-six point one percent of the Dental Surgeons have recognized septum syndrome as an emergency. The management of the emergency, followed by the completion of the comprehensive care later represents the attitude of 71.6% of the dentists. Sixty-four point two percent of dentists remove irritating elements under gingival, 80.6% prescribe an antiinflammatory, 38.8% prescribe chlorhexidine gel and 26.9% reconstruct the point of contact. Conclusion: This study demonstrates that Dental Surgeons in general have adequate average knowledge and attitude for their management of septal syndrome.

A Case of Septo-Optic Dysplasia Resulting in Central Diabetes Insipidus and Nonobstructive Bilateral Hydronephrosis / 대한내과학회지

A 27-year-old male with nonobstructive hydronephrosis was referred from the urology department for polyuria evaluation and management. The patient was hospitalized for urinary tract infection and cystostomy was performed due to neurogenic bladder of unknown origin. The patient was of short stature and had visual impairment. From the interview, we discovered he had been suffering from polyuria and polydipsia for more than 20 years. Urine output was 13 L/day and urine osmolarity was 85 mOsm/kg. The results of a water deprivation test were consistent with central diabetes insipidus. Septo-optic dysplasia (SOD) was observed on brain magnetic resonance imaging (MRI). SOD is a very rare condition characterized by agenesis of the septum pellucidum or corpus callosum, which may cause optic nerve aplasia or hypoplasia, midbrain abnormalities and/or hypopituitarism. After desmopressin treatment, polyuria and hydronephrosis were improved. We report a case of a 27-year-old male diagnosed with SOD including diabetes insipidus, resulting in nonobstructive hydronephrosis.

Hipoplasia septo-óptica-hipofisária em paciente com septo pelúcido normal porém com risco de morte neonatal e a participação potencial do fator de transcrição hipofisário HESX1 / The potential involvement of the pituitary transcription factor HESX1 in the septo-optic-pituitary hypoplasia with normal septum pellucidum but life-threatening neonatal phenotype

A displasia septo-óptica (DSO) é uma síndrome do desenvolvimento considerada heterogênea, pois envolve anomalias da linhamédia do cérebro associadas a disfunções oftalmológicas, neurológicas e do eixo hipotálamo-hipófise. O fenótipo é altamentevariável dificultando a classificação da doença. Relatamos um caso de hipopituitarismo neonatal grave que levou à descobertade malformações cerebrais e hipoplasia do nervo óptico, sendo caracterizada assim a síndrome DSO-like. Mesmo em presençade um septo pelúcido normal e com poucas alterações na ressonância magnética, este paciente apresentou um fenótipo endócrinode alto risco de morte no período neonatal. Mutações genéticas têm sido raramente descritas no HESX1 e estão associadas avárias deficiências hormonais hipofisárias combinadas com a DSO. O gene HESX1 codifica um fator de transcrição pertencenteà classe de genes chamados homeobox. A partir deste gene candidato, foi isolada a região codificadora no DNA para análise porsequenciamento. Este relato de caso com seguimento clínico de 7 anos e estudo genético preliminar apresenta uma discussãoda investigação diagnóstica a partir do quadro inicial, destacando as alterações de neuroimagem encontradas nesta síndrome.

Septo-optic dysplasia / Displasia septo-óptica

Septo-optic dysplasia (SOD), also referred to as de Morsier syndrome, is a rare congenital condition, characterized by two of the classic triad features: midline brain abnormalities, optic nerve hypoplasia (ONH) and pituitary endocrine dysfunction. We report 5 children with SOD, originally referred to be evaluated due to short stature, who also presented bilateral optic nerve hypoplasia, nystagmus and development delay. In 4 of the patients, we identified neuroimaging abnormalities of the hypothalamo-pituitary axis such as anterior pituitary hypoplasia (3/5), ectopic posterior pituitary (4/5), thin or absent stalk (3/5) and empty sella (1/5). We also encountered diverse pituitary deficiencies: growth hormone (3/5), adrenocorticotropic hormone (3/5), thyroid-stimulating hormone (2/5) and antidiuretic hormone (1/5). Only one child presented intact pituitary function and anatomy. Although rare, SOD is an important cause of congenital hypopituitarism and it should be considered in children with optic nerve hypoplasia or midline brain abnormalities for early diagnosis and treatment.

A displasia septo-óptica (DSO, síndrome de Morsier) é uma condição congênita rara definida por dois critérios da tríade: defeitos de linha média, hipoplasia de nervo óptico e insuficiência hipotálamo-hipofisária. Descrevemos 5 casos de DSO, encaminhados por baixa estatura, com hipoplasia dos nervos ópticos, nistagmo e atraso global do desenvolvimento. Destes, 4 possuem alteração na ressonância magnética de sela túrcica e insuficiência hipotálamo-hipofisária, tendo sido observada adeno-hipófise hipoplásica (3/5), neuro-hipófise ectópica (4/5), haste afilada/ausente (3/5) e sela vazia (1/5), além de déficit dos eixos somatotrófico (3/5), adrenocorticotrófico (3/5), tireotrófico (2/5) e do hormônio antidiurético (1/5). Apenas um paciente não apresenta alteração anatômica ou funcional do eixo hipotálamo-hipofisário. Embora rara, a DSO é causa importante de hipopituitarismo congênito, devendo ser considerada em crianças com hipoplasia de nervo óptico ou defeito de linha média para seu diagnóstico e tratamento precoces, evitando seqüelas graves.

Displasia septo-optica. Evaluación clínica, endocrinológica y neuro-radiológica. Seguimiento de 46 pacientes pediátricos / Septo-optic dysplasia. Clinical, endocrinological, and neuroradiological evaluation. Follow-up of 46 pediatric patients

La displasia septo-óptica (DSO) es una condición rara y altamente heterogénea, definida por la combinación de hipoplasia del nervio óptico (HNO), malformaciones cerebrales de la línea media, tales como aplasia/hipoplasia de septum pellucidum y cuerpo calloso, e insuficiencia hipotálamo-hipofisaria de grado variable. Se realizó un trabajo que tuvo como objetivo caracterizar la población de pacientes con diagnóstico de DSO seguidos en nuestro Hospital durante 7 años. Se incluyeron 46 pacientes (18 mujeres) que fueron divididos en 2 grupos, según tuviesen o no insuficiencia hipotálamo-hipofisaria (IHH). El 58.7% (n=27) presentó IHH de algún tipo, mientras que el 41.3% (n=19) no la presentó. En aquellos 19 pacientes con IHH se diagnosticaron deficiencia de GH y TSH (85.1%) y de ACTH (48.1%). La longitud corporal (mediana) del grupo con IHH fue más baja (p = 0,01) que la del grupo sin IHH, a pesar de que la edad fue menor a 2 años en todos los casos. Los pacientes fueron seguidos 1,3-8,3 años. Se observaron incidencias similares de agenesia del cuerpo calloso, del septum pellucidum, y ventriculomegalia, pero las alteraciones del desarrollo cortical se observaron con mayor frecuencia en los pacientes sin IHH. La ictericia neonatal, convulsiones y/o hipoglucemia, y micropene en neonatos y lactantes con DSO se presentaron en el subgrupo con IHH. El 58,7% de los pacientes con DSO presentaron algún grado de insuficiencia hipotálamo-hipofisaria. En la mayoría de los casos el diagnóstico de IHH no se realizó en el momento de aparición de los síntomas, sino más tardíamente en su seguimiento. En el 45% de los pacientes se evaluaron alteraciones radiológicas del SNC, específicamente en la región hipofisaria. Una fracción importante de las deficiencias de TSH/T4 (36,4%), GH (50%) y ACTH (23%) aparecieron mas tardíamente en el curso de la evolución. En 10 niños con déficit de hormona de crecimiento (2 tests farmacológicos sin respuesta) se realizó el tratamiento sustitutivo con rhGH (durante un periodo de 4±3 años), observándose una mejoría promedio de + 1,5 SDS en la talla de estos pacientes. En conclusión, la hipoplasia neonatal de nervios ópticos, asociada o no a ictericia e hipoglucemia, debe ser un signo de alarma para el diagnóstico de DSO, con riesgo de insuficiencia suprarrenal, shock y muerte, y puede requerir, por lo tanto, urgente tratamiento. Las deficiencias pueden aparecer en el curso de la evolución, a pesar del carácter congénito de la anomalía. Finalmente, se deben sustituir las deficiencias hormonales y tener presente que el tratamiento con rhGH puede mejorar la talla final en estos pacientes (AU)

Septo-optic dysplasia (SOD) is a rare and highly heterogeneous condition consisting of a combination of optic nerve hypoplasia (ONH), midline brain abnormalities, such as aplasia/hypoplasia of the septum pellucidum (ASP) and corpus callosum; and variable degree of hypoyalamo-pituitary insufficiency. The aim of this study was to characterize a population of SOD patients diagnosed and followed at the Garrahan Pediatric Hospital, from 1989 to 2006. We included 46 patients (18 females), that were divided into two groups according to the presence or absence of hypothalamic-pituitary insufficiency (IHH). Fifty nine% of SOD patients presented with IHH. GH and TSH deficiencies were diagnosed in 85.1% of IHH patients, while ACTH deficiency was found in 48.1%. Height (median) for the IHH group was shorter (p = 0,01) than for the group without IHH. Patients were followed for 1.3-8.3 years. Similar incidence of corpus callosum and/or septum pellucidum agenesis and ventriculomegaly were found in the two groups, but we observed more association with cortical developmental disorders in patients without IHH. In newborns, the association of ophthalmologic disorders and jaundice, seizures and/or hypoglycemia and micropene should frequently lead to the diagnosis of SOD and IHH. While 58,7% of DSO patients presented with hypothalamic-pituitary deficiency, only 45% of them showed sellar radiological abnormalities. Although SOD is a congenital disease, hormonal deficiencies may appear during follow-up. In 10 children with SOD and GH deficiency, rhGh treatment (for 4±3 years) improved height in 1.5 SDSs. In conclusion: in newborns with nerve optic hypoplasia, associated or not with jaundice, seizures and hypoglycaemia, the diagnosis of SOD and IHH should be considered. Treatment could be an emergency need because of risk of adrenal insufficiency and hypoglycemia (AU)

Molecular analysis of the PROP1 and HESX1 genes in patients with septo-optic dysplasia and/or pituitary hormone deficiency / Análise molecular dos genes PROP1 e HESX1 em pacientes com displasia septo-ótica e/ou deficiência hormonal hipofisária

OBJECTIVE: The present study aimed at evaluating the PROP1 and HESX1 genes in a group of patients with septo-optic dysplasia (SOD) and pituitary hormone deficiency (combined - CPHD; isolated GH deficiency - GHD). Eleven patients with a clinical and biochemical presentation consistent with CPHD, GHD or SOD were evaluated. SUBJECTS AND METHODS: In all patients, the HESX1 gene was analyzed by direct sequence analysis and in cases of CPHD the PROP1 gene was also sequenced. RESULTS: A polymorphism (1772 A > G; N125S) was identified in a patient with SOD. We found three patients carrying the allelic variants 27 T > C; A9A and 59 A > G; N20S in exon 1 of the PROP1 gene. Mutations in the PROP1 and HESX1 genes were not identified in these patients with sporadic GHD, CPHD and SOD. CONCLUSION: Genetic alterations in one or several other genes, or non-genetic mechanisms, must be implicated in the pathogenic process.

OBJETIVO: O presente estudo teve como objetivo avaliar os genes PROP1 e HESX1 em um grupo de pacientes com displasia septo-óptica (DSO) e deficiência hormonal hipofisária (combinada - DHHC; ou deficiência isolada de GH - DGH). Onze pacientes com apresentação clínica e bioquímica consistente com DHHC, DGH ou DSO foram avaliados. SUBJECTS AND METHODS: Em todos os pacientes, o gene HESX1 foi analisado pelo sequenciamento direto e, nos casos de DHHC, o gene PROP1 foi também sequenciado. RESULTADOS: Um polimorfismo no gene HESX1 (1772 A > G; N125S) foi identificado em um paciente com DSO. Foram encontrados três pacientes portadores da variação alélica 27 T > C; A9A e 59 A > G; N20S no éxon 1 do gene PROP1. Mutações no gene PROP1 e HESX1 não foram identificadas nesses pacientes com DGH, DHHC e DSO esporádicos. CONCLUSÃO: Alterações genéticas em um ou diversos outros genes ou mecanismos não genéticos devem estar implicados nesse processo patogênico.

Hipoplasia del nervio óptico y displasia septo-óptica / Optic nerve hypoplasia and septo-optic dysplasia

La displasia septo-óptica o síndrome de De Morsier es un trastornopoco usual del desarrollo embrionario. Consiste en la hipoplasia de uno o ambos nervios ópticos, malformacionescerebrales de la línea media y disfunción hipotálamo-hipofisaria, la cual es inconstante. En el presente trabajo se describen los hallazgos de 9 pacientes con displasia septo-óptica.

A Neonatal Case of Septo-Optic Dysplasia with Schizencephaly

Septo-optic dysplasia is a rare congenital disorder characterized by the absence of the septum pallucidum, hypoplasia of the optic chiasma and nerves, and various types of hypothalamic-pituitary dysfunction. Schizencephaly is an abnormal cleft in the brain, lined with gray matter which may communicate with the ventricular system. Septo-optic dysplasia with schizencephaly is associated with endocrinologic disorders, visual impairment, mental retardation, and seizures. We report a case of septo-optic dysplasia with schizencephaly which was diagnosed in the early neonatal period.

De Morsier syndrome associated with periventricular nodular heterotopia: case reporte

INTRODUCTION: Septo-optic dysplasia (De Morsier syndrome) is defined as the association between optic nerve hypoplasia, midline central nervous system malformations and pituitary dysfunction. CASE REPORT: Third child born to nonconsanguineous parents, female, adequate pre-natal medical care, cesarean term delivery due to breech presentation, Apgar score 3 at the first minute and 8 at 5 minutes, symptomatic hypoglycemia at 18 hours. Neurological follow-up identified a delay in acquisition of motor and language developmental milestones. Epileptic generalized seizures began at 12 months and were controlled with phenobarbital. EEG was normal. MRI revealed agenesis of the pituitary stalk, hypoplasia of the optic chiasm and periventricular nodular heterotopia. Ophthalmologic evaluation showed bilateral optic disk hypoplasia. Endocrine function laboratory tests revealed primary hypothyroidism and hyperprolactinemia. CONCLUSION: The relevance of this case report relies on its uniqueness, since periventricular heterotopia had not been described in association with septo-optic dysplasia until 2006.

INTRODUÇÃO: Displasia septo-óptica (síndrome de De Morsier) é definida como a associação entre hipoplasia do nervo óptico, malformações de linha média do sistema nervoso central e disfunção pituitária. RELATO DE CASO: Terceiro filho, pais não consangüíneos, sexo feminino, pré-natal adequado, parto cesário a termo por apresentação pélvica, Apgar 3 no primeiro minuto e 8 no quinto minuto, hipoglicemia sintomática com 18 horas de vida. Durante o acompanhamento neurológico identificou-se atraso na aquisição dos marcos de desenvolvimento motor e linguagem. Crises epilépticas generalizadas iniciaram com 12 meses de vida sendo controladas com fenobarbital. EEG era normal. Ressonância magnética revelou agenesia de haste pituitária, hipoplasia de quiasma óptico e heterotopia nodular periventricular. Avaliação oftalmológica demonstrou hipoplasia bilateral de disco óptico. Investigação da função endócrina revelou hipotireoidismo primário e hiperprolactinemia. CONCLUSÃO: A relevância deste relato reside em seu ineditismo, já que heterotopia periventricular não havia sido descrita em associação com displasia septo-óptica até 2006.

Septo-optic dysplasia associated with abnormal pubertal development.

Septo-optic dysplasia (SOD) is a congenital anomaly, that is characterized by a triad of optic nerve hypoplasia, structural brain defects, and hypothalamic-pituitary dysfunction. This condition is very rare and it has never been reported in a Thai population. In the present report, the authors described two SOD cases that presented with primary amenorrhea and abnormal pubertal development. Clinical features. Possible etiology of this condition was reviewed

Clinical Manifestations of Optic Nerve Hypoplasia

PURPOSE: To estimate the baseline demographic and ocular characteristics of patients with optic nerve hypoplasia (ONH), and to analyze the different features and frequency of coexistent CNS abnormalities and pituitary hormone deficiency. METHODS: The authors reviewed the medical records of the patients who were seen between January 1988 and July 2005. Eyes with disc-to-macula / disc diameter ratio of 3.0 or more were eligible. The study comprised 70 patients (45 male, 25 female) and the average age was 6.4 years. RESULTS: Ocular manifestations included strabismus and nystagmus in 60 patients (85.7%) and 23 patients (32.9%), respectively. Eighty-four patients (87.5%) had visual acuity of 0.3 or less. Neuroradiologic examination of 27 patients revealed two with septo-optic dysplasia, two with pituitary hypoplasia, one with an absence of corpus callosum, one with diffuse encephalomalacia, one with a cerebral infarction in the right cerebral hemisphere, and one with a cerebellar injury. Of 12 patients who had undergone a clinical laboratory test, two had isolated growth hormone deficiency, one had a combined deficiency of growth hormone and gonadotropin and one had a combined deficiency of growth hormone and thyrotropin. CONCLUSIONS: Ocular features frequently associated with ONH are strabismus, nystagmus and poor vision. ONH is often associated with a wide variety of central nervous system abnormalities and pituitary hormone defect, so a systematic approach to patients with ONH is always recommended.

Anoftalmía bilateral por displasia septo-óptica: síndrome de De Morsier / Anophthalmia bilateral caused by septo-optic dysplasia: the De Morsier syndrome

Introducción: La displasia septo-óptica es una enfermedad congénita caracterizada por hipoplasia de uno o ambos nervios ópticos que se acompaña de malformaciones cerebrales de la línea media y disfunción hipotálamo-hipofisiaria. Objetivo: Mostrar un caso ilustrativo del estudio de pacientes con anoftalmía y retraso psicomotor, con énfasis en los diagnósticos diferenciales. Caso clínico: Lactante femenina de 18 meses de edad con anoftalmía bilateral, asociada con ausencia en el desarrollo de los nervios ópticos e hipoplasia del septum pellucidum corroborada por tomografía craneal, el cariotipo normal descartó la posibilidad de cromosomopatía. Conclusión: Caso clínico esporádico de displasia septo-óptica: síndrome de De Morsier extremo sin manifestaciones neurológicas o endocrinológicas.