High prevalence of pituitary hormone deficiency in both unilateral and bilateral optic nerve hypoplasia

Dahl, Sara; Wiberg, Maria Kristoffersen; Fahnehjelm, Kristina Teär; Sävendahl, Lars; Wickström, Ronny

doi:10.1111/apa.14751

Cited by 9 publications

(4 citation statements)

References 31 publications

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“…endocrinopathies, or developmental outcomes [3]. In contrast, the onset of pituitary deficits has been extensively associated with ONH, regardless of its laterality [3,31,35]. A severe visual phenotype with blindness has been recently reported as a risk factor for hypopituitarism in a large cohort of patients with ONH [31], more than the presence of bilateral (vs unilateral) ONH, as also confirmed in our study.…”

Section: Tablesupporting

confidence: 86%

Endocrine morbidity in midline brain defects: Differences between septo-optic dysplasia and related disorders

et al. 2020

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Background: Septo-optic dysplasia (SOD) is a heterogeneous congenital condition. The aim of this study was to investigate the clinical phenotypes of a large cohort of children with SOD, Multiple Pituitary Hormone Deficiency (MPHD) and Optic Nerve Hypoplasia (ONH), with a focus on endocrine testing. Methods: Retrospective single-centre longitudinal study of children with SOD (n:171), MPHD (n:53) and ONH (n:35). SOD+ and SOD-indicate patients with or without hypopituitarism, respectively. Findings: All deficits were more frequent and occurred earlier in MPHD than SOD+ [Hazard Ratios (HR): 0¢63 (0¢45,0¢89) for GH, 0¢48(0¢34,0¢69) for TSH, 0¢55(0¢38,0¢80) for ACTH, 0¢28(0¢11,0¢68) for gonadotropins], except Diabetes Insipidus (DI) [HR: 2¢27(0¢88,5¢9)]. Severe hypothalamo-pituitary (H-P) abnormalities were more frequent in MPHD [80¢0% vs 41¢6%, p<0¢0001 for Ectopic Posterior Pituitary (EPP)]. Stalk and PP abnormalities were associated with more severe endocrine phenotypes and placed a subgroup of SOD+ at risk of developing deficits earlier. SOD and ONH shared heterogeneous phenotypes ranging from pubertal delay to precocity and from leanness to extreme obesity, whilst MPHD had GnD and obesity only. Mortality was recorded in 4¢2% (6/144) SOD and 3¢2% (1/31) ONH, and only in patients with multisystem phenotypes. Interpretation: More than a single disease, SOD represents a spectrum of malformative conditions involving different brain structures and characterised by a dynamic and sequential nature of endocrine. In contrast, MPHD displays a more homogeneous phenotype of (mainly) anterior pituitary early-onset failure. Stalk and PP abnormalities place a subgroup of SOD+ at a higher risk of early-onset deficits. Additionally, there are striking differences between the SOD and MPHD cohorts in terms of pubertal progression. The shared phenotypes between ONH and SOD could be partly explained by common hypothalamic dysfunction. The differences between the cohorts are important as they may aid in planning management and preventing morbidity by dictating earlier interventions. Funding: M.C., M.G., and N.I. were supported by the European Society of Paediatric Endocrinology (ESPE) through ESPE Clinical Fellowships.

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Section: Tablesupporting

confidence: 86%

Endocrine morbidity in midline brain defects: Differences between septo-optic dysplasia and related disorders

et al. 2020

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“…In Stockholm, a population-based, cross-sectional cohort of children and young adults with ONH has been identified and phenotyped [1,5,6]. The diagnosis of ONH was confirmed when there was a small optic disc in combination with visual deprivation and/or a visual field defect [1].…”

Section: Study Population and Participant Demographicsmentioning

confidence: 99%

“…The prevalence has been reported to be 10.9/100 000 in Northwest England [4] and 17.3/100 000 in Stockholm, Sweden [1]. Individuals with ONH often have coexisting pituitary hormone deficiencies, intellectual disability, autism, and other brain malformations [3,5,6].…”

Section: Introductionmentioning

confidence: 99%

Whole genome sequencing unveils genetic heterogeneity in optic nerve hypoplasia

et al. 2020

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Optic nerve hypoplasia (ONH) is a congenital malformation with a reduced number of retinal ganglion cell axons in a thin optic nerve. It is a common cause of visual impairment in children and ONH is associated with neurodevelopmental disorders, pituitary hormone deficiencies, and brain malformations. In most cases, the aetiology is unknown, but both environmental factors and genetic causes have been described. This study aimed to identify genetic variants underlying ONH in a well-characterised cohort of individuals with ONH. We performed array comparative genomic hybridization and whole genome sequencing in 29 individuals with ONH. Rare variants were verified by Sanger sequencing and inheritance was assessed in parental samples. We identified 11 rare single nucleotide variants (SNVs) in ten individuals, including a homozygous variant in KIF7 (previously associated with Joubert syndrome), a heterozygous de novo variant in COL4A1 (previously described in an individual with porencephaly), and a homozygous variant in COL4A2. In addition, one individual harboured a heterozygous variant in OPA1 and a heterozygous variant in COL4A1, both were inherited and assessed as variants of unknown clinical significance. Finally, a heterozygous deletion of 341 kb involving exons 7-18 of SOX5 (associated with Lamb-Schaffer syndrome) was identified in one individual. The overall diagnostic yield of pathogenic or likely pathogenic variants in individuals with ONH using whole genome sequencing was 4/ 29 (14%). Our results show that there is a genetic heterogeneity in ONH and indicate that genetic causes of ONH are not rare. We conclude that genetic testing is valuable in a substantial proportion of the individuals with ONH, especially in cases with non-isolated ONH.

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“…Only more recent papers have described overlapping and comorbidity between VI and ASD considering social, linguistic and communicative development in children with blindness and not only just the described behavioral patterns. These more recent papers consider the new conceptual model of autism and the authors focus assessment on the three main clinical features of autism (impaired social interaction, communication, and restricted and repetitive behavior) [ 8 , 14 , 15 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Autism and Visual impairment: A First Approach to a Complex Relationship

Pili¹,

Zolo²,

Farris³

et al. 2021

CPEMH

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Since the first half of the 20th century there has been an interest in the study of the relationship between autism and autistic-like clinical features and with visual impairments. Autism Spectrum disorders are one of the more worldwide-studied neurodevelopmental disorder with an increasing prevalence in the last ten years. Visual impairment is a condition which derives from several causes (genetic, constitutional, injuries, nutritional and environmental ones). Again, it is a kind of spectrum and an overarching category, because visual impairments range from refractive errors (myopia, hyperopia, astigmatism), to amblyopia, strabismus, and to partial and total blindness. Since the first study of Keeler (1956) which described autistic-like patterns in five preschool children who were totally blind due to retinopathy of prematurity (ROP), a growing number of researchers addressed the relationship between autism and visual impairment. In this paper we focused on it, aiming to discuss on some lessons learned in this field and to discuss some open questions since the first research in this field.

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High prevalence of pituitary hormone deficiency in both unilateral and bilateral optic nerve hypoplasia

Cited by 9 publications

References 31 publications

Endocrine morbidity in midline brain defects: Differences between septo-optic dysplasia and related disorders

Endocrine morbidity in midline brain defects: Differences between septo-optic dysplasia and related disorders

Whole genome sequencing unveils genetic heterogeneity in optic nerve hypoplasia

Autism and Visual impairment: A First Approach to a Complex Relationship

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