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Arquivos de Neuro-psiquiatria Jun 2010Septo-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...
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.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Hypopituitarism; Hypothalamo-Hypophyseal System; Magnetic Resonance Imaging; Male; Sella Turcica; Septo-Optic Dysplasia
PubMed: 20602044
DOI: 10.1590/s0004-282x2010000300014 -
European Journal of Human Genetics :... Apr 2010This review summarises the key clinical features of septo-optic dysplasia (SOD), the significant inroads that progress in genetics has made into our understanding of the... (Review)
Review
This review summarises the key clinical features of septo-optic dysplasia (SOD), the significant inroads that progress in genetics has made into our understanding of the aetiology of the condition over the last decade, and the pitfalls and challenges that we face in the management of these phenotypically variable patients.
Topics: Humans; Septo-Optic Dysplasia
PubMed: 19623216
DOI: 10.1038/ejhg.2009.125 -
Human Mutation Sep 2018Malan syndrome is an overgrowth disorder described in a limited number of individuals. We aim to delineate the entity by studying a large group of affected individuals....
Malan syndrome is an overgrowth disorder described in a limited number of individuals. We aim to delineate the entity by studying a large group of affected individuals. We gathered data on 45 affected individuals with a molecularly confirmed diagnosis through an international collaboration and compared data to the 35 previously reported individuals. Results indicate that height is > 2 SDS in infancy and childhood but in only half of affected adults. Cardinal facial characteristics include long, triangular face, macrocephaly, prominent forehead, everted lower lip, and prominent chin. Intellectual disability is universally present, behaviorally anxiety is characteristic. Malan syndrome is caused by deletions or point mutations of NFIX clustered mostly in exon 2. There is no genotype-phenotype correlation except for an increased risk for epilepsy with 19p13.2 microdeletions. Variants arose de novo, except in one family in which mother was mosaic. Variants causing Malan and Marshall-Smith syndrome can be discerned by differences in the site of stop codon formation. We conclude that Malan syndrome has a well recognizable phenotype that usually can be discerned easily from Marshall-Smith syndrome but rarely there is some overlap. Differentiation from Sotos and Weaver syndrome can be made by clinical evaluation only.
Topics: Abnormalities, Multiple; Adolescent; Adult; Bone Diseases, Developmental; Child; Child, Preschool; Chromosome Deletion; Congenital Hypothyroidism; Craniofacial Abnormalities; Developmental Disabilities; Exons; Female; Hand Deformities, Congenital; Humans; Intellectual Disability; Male; Megalencephaly; Mutation, Missense; NFI Transcription Factors; Phenotype; Septo-Optic Dysplasia; Sotos Syndrome; Young Adult
PubMed: 29897170
DOI: 10.1002/humu.23563 -
Frontiers in Pediatrics 2020Congenital hypopituitarism (CH) is characterized by a deficiency of one or more pituitary hormones. The pituitary gland is a central regulator of growth, metabolism,... (Review)
Review
Congenital hypopituitarism (CH) is characterized by a deficiency of one or more pituitary hormones. The pituitary gland is a central regulator of growth, metabolism, and reproduction. The anterior pituitary produces and secretes growth hormone (GH), adrenocorticotropic hormone, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, and prolactin. The posterior pituitary hormone secretes antidiuretic hormone and oxytocin. The incidence is 1 in 4,000-1 in 10,000. The majority of CH cases are sporadic; however, a small number of familial cases have been identified. In the latter, a molecular basis has frequently been identified. Between 80-90% of CH cases remain unsolved in terms of molecular genetics. Several transcription factors and signaling molecules are involved in the development of the pituitary gland. Mutations in any of these genes may result in CH including , and . Over the last 5 years, several novel genes have been identified in association with CH, but it is likely that many genes remain to be identified, as the majority of patients with CH do not have an identified mutation. Genotype-phenotype correlations are difficult to establish. There is a high phenotypic variability associated with different genetic mutations. The clinical spectrum includes severe midline developmental disorders, hypopituitarism (in isolation or combined with other congenital abnormalities), and isolated hormone deficiencies. Key investigations include MRI and baseline and dynamic pituitary function tests. However, dynamic tests of GH secretion cannot be performed in the neonatal period, and a diagnosis of GH deficiency may be based on auxology, MRI findings, and low growth factor concentrations. Once a hormone deficit is confirmed, hormone replacement should be started. If onset is acute with hypoglycaemia, cortisol deficiency should be excluded, and if identified this should be rapidly treated, as should TSH deficiency. This review aims to give an overview of CH including management of this complex condition.
PubMed: 33634051
DOI: 10.3389/fped.2020.600962 -
Neuro-ophthalmology (Aeolus Press) 2021A 3-month-old boy was referred for assessment and management of apparently absent ocular globes. Ocular examination showed small orbits with apparently absent globes,...
A 3-month-old boy was referred for assessment and management of apparently absent ocular globes. Ocular examination showed small orbits with apparently absent globes, small conjunctival cul-de-sac, shallow fornices, microblepharon and sunken eyelids. Magnetic resonance imaging of the orbit and brain revealed bilateral extreme microphthalmia, replacement of the optic nerves by disorganised rudimentary tissue tufts, hypoplastic orbits and extraocular muscles, an absent septum pellucidum and an absent corpus callosum. A pituitary hormonal essay showed decreased adrenocorticotropic hormone and thyroid-stimulating hormone. Septo-optic dysplasia has been rarely reported to be associated with microphthalmia. Timely treatment with hydrocortisone and levothyroxine is essential to prevent Addisonian crisis from the stress and pain that may accompany insertion of socket expanders.
PubMed: 34483412
DOI: 10.1080/01658107.2020.1791910 -
Genes Jun 2022Septo-optic dysplasia (SOD) is a developmental phenotype characterized by midline neuroradiological anomalies, optic nerve hypoplasia, and pituitary anomalies, with a...
Septo-optic dysplasia (SOD) is a developmental phenotype characterized by midline neuroradiological anomalies, optic nerve hypoplasia, and pituitary anomalies, with a high degree of variability and additional systemic anomalies present in some cases. While disruption of several transcription factors has been identified in SOD cohorts, most cases lack a genetic diagnosis, with multifactorial risk factors being thought to play a role. Exome sequencing in a cohort of families with a clinical diagnosis of SOD identified a genetic diagnosis in 3/6 families, de novo variants in , , and , and explored variants of uncertain significance in the remaining three. The outcome of this study suggests that investigation for a genetic etiology is warranted in individuals with SOD, particularly in the presence of additional syndromic anomalies and when born to older, multigravida mothers. The identification of causative variants in and further expands the phenotypic spectra associated with these genes and reveals novel pathways to explore in septo-optic dysplasia.
Topics: Humans; Phenotype; Septo-Optic Dysplasia; Superoxide Dismutase
PubMed: 35885948
DOI: 10.3390/genes13071165 -
European Journal of Endocrinology Apr 2022An Endo-European Reference Network guideline initiative was launched including 16 clinicians experienced in endocrinology, pediatric and adult and 2 patient...
Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline.
An Endo-European Reference Network guideline initiative was launched including 16 clinicians experienced in endocrinology, pediatric and adult and 2 patient representatives. The guideline was endorsed by the European Society for Pediatric Endocrinology, the European Society for Endocrinology and the European Academy of Andrology. The aim was to create practice guidelines for clinical assessment and puberty induction in individuals with congenital pituitary or gonadal hormone deficiency. A systematic literature search was conducted, and the evidence was graded according to the Grading of Recommendations, Assessment, Development and Evaluation system. If the evidence was insufficient or lacking, then the conclusions were based on expert opinion. The guideline includes recommendations for puberty induction with oestrogen or testosterone. Publications on the induction of puberty with follicle-stimulation hormone and human chorionic gonadotrophin in hypogonadotropic hypogonadism are reviewed. Specific issues in individuals with Klinefelter syndrome or androgen insensitivity syndrome are considered. The expert panel recommends that pubertal induction or sex hormone replacement to sustain puberty should be cared for by a multidisciplinary team. Children with a known condition should be followed from the age of 8 years for girls and 9 years for boys. Puberty induction should be individualised but considered at 11 years in girls and 12 years in boys. Psychological aspects of puberty and fertility issues are especially important to address in individuals with sex development disorders or congenital pituitary deficiencies. The transition of these young adults highlights the importance of a multidisciplinary approach, to discuss both medical issues and social and psychological issues that arise in the context of these chronic conditions.
Topics: Child; Female; Gonadal Steroid Hormones; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Pituitary Diseases; Puberty; Puberty, Delayed; Testosterone; Young Adult
PubMed: 35353710
DOI: 10.1530/EJE-22-0073 -
Radiology Case Reports Sep 2022Septo-optic dysplasia (SOD) is a rare congenital disorder occurring in only 1 in 10,000 live births. Initially it was described in 1941 by Reeves and further discussed...
Septo-optic dysplasia (SOD) is a rare congenital disorder occurring in only 1 in 10,000 live births. Initially it was described in 1941 by Reeves and further discussed by the French-Swiss neurologist de Morsier (1956) as the disease further addressed his name. SOD is a combination of triads of hypoplasia of the optic nerve, agenesis of midline brain structures, and hypoplasia of the hypothalamic-pituitary axis. The pathophysiology of this rare congenital anomaly is yet to be understood, with some hypotheses in order to establish the diagnosis. The management modality depends on the presentation of the disease and requires a multidisciplinary approach. While most SOD patients present with visual, neurological, or endocrine abnormalities, in our case the patient was diagnosed incidentally while following up after an episode of acute respiratory distress syndrome and sepsis. We aim to highlight the aspects of clinical presentation in a patient with SOD and the importance of a multimodality follow-up approach.
PubMed: 35801123
DOI: 10.1016/j.radcr.2022.06.002 -
Cureus Dec 2018Septo-optic dysplasia plus is a rare congenital syndrome characterized by the classic triad of optic nerve hypoplasia, hypothalamic-hypophyseal dysfunction, and midline...
Septo-optic dysplasia plus is a rare congenital syndrome characterized by the classic triad of optic nerve hypoplasia, hypothalamic-hypophyseal dysfunction, and midline abnormalities, with associated malformations of cortical development. Clinical manifestations include optic nerve disease, epilepsy, intellectual delay, and endocrine dysfunction. We present the case of an 18-year-old man with a history of seizures, growth hormone deficiency, and optic nerve disease that was diagnosed with septo-optic dysplasia plus syndrome with characteristic imaging findings.
PubMed: 30800538
DOI: 10.7759/cureus.3727