中隔視神経形成異常症／ドモルシア症候群

CONTEXT: The pathophysiology of hypothalamic obesity (HyOb) remains incompletely understood with no effective treatments. OBJECTIVE: We examined differences in appetite-regulating hormone concentrations between patients with HyOb, common obesity, and lean controls. DESIGN: Multiway cross-sectional case-control study of patients aged 2 through 19 years. SETTING: Two tertiary pediatric endocrinology centers. PATIENTS: Cases were obese (body mass index [BMI] > +2 SD score [SDS], "HyOb") and lean ("HyLean") patients with congenital (septo-optic dysplasia) or acquired (suprasellar brain tumor) hypothalamic disorders. Controls had common obesity ("Ob") or nonhypothalamic disorders and normal BMI ("Lean"). MAIN OUTCOME MEASURES: Relationships between the Dykens' Hyperphagia Questionnaire Score (DHQS), plasma or serum concentrations of leptin, insulin, α-melanocyte stimulating hormone (αMSH), brain-derived neurotrophic factor, oxytocin, acylated ghrelin, agouti-related peptide and copeptin, and BMI SDS. RESULTS: Dykens' Hyperphagia Questionnaire Score did not differ between HyOb and Ob patients (24 [17-34] vs 24 [18-31]) but correlated with BMI SDS in patients with hypothalamic disorders (P = 0.02). HyOb and Ob patients exhibited similarly increased anorexigens (insulin, leptin) and decreased orexigens (ghrelin, agouti-related peptide) compared to HyLean and Lean patients. The rate of BMI increase was independently associated with lower αMSH (β = -0.23 [-0.36 to -0.11], P = .0007) and ghrelin (β=-0.004 [-0.01 to 0.00], P = .001) concentrations, suggesting that αMSH replacement may be a therapeutic target for HyOb. HyLean patients demonstrated intermediate insulin responses to glucose compared to other subcohorts. CONCLUSION: In our cohort, patients with HyOb appeared indistinguishable from Ob in terms of their appetite and appetite-regulating neuroendocrine circuitry. Higher αMSH concentrations are associated with reduced weight gain and may be a target for therapeutic intervention.

Septo-optic dysplasia (SOD) is a heterogeneous neurodevelopmental disorder classically defined by optic nerve hypoplasia, hypothalamo-pituitary dysfunction, and midline brain abnormalities, although the full triad is not consistently present. This review synthesises current evidence on the developmental, endocrine, ophthalmic, and neuroradiological dimensions of the SOD/optic nerve hypoplasia spectrum. Shared embryological origins of the optic pathways, hypothalamus, and pituitary, together with disruption of inductive signalling pathways and pathogenic variants in developmental regulators including SOX2, HESX1, SOX3, and OTX2, provide a mechanistic basis for combined ocular and pituitary phenotypes. Clinically, affected children may present with nystagmus, strabismus, visual impairment, neonatal hypoglycaemia, or evolving pituitary hormone deficiencies, and remain at risk of neurodevelopmental morbidity. Neuroradiological studies have expanded the phenotype beyond classical midline defects to include malformations of cortical development and SOD-plus presentations. Current evidence supports longitudinal endocrine surveillance, detailed ophthalmic assessment, and multidisciplinary care, including timely hormone replacement and developmental support where indicated.

PURPOSE: Children with vision differences face unique challenges in accessing classroom communication, which can affect language development, academic achievement, and social participation. To ensure effective communication, professionals must understand each child's diverse access needs and individual preferences. Professionals must also be aware of the nature of the child's lived visual experience, including the strategies that allow the child with low vision to access sustained and meaningful vision, compared to those strategies preferred by the child who is blind. METHOD: This tutorial discusses a comprehensive framework that is created by combining the International Classification of Functioning, Disability and Health (ICF) and the Expanded Core Curriculum (ECC). The ICF identifies barriers and facilitators to functioning and participation, while the ECC supports independence, participation, and communication through relevant interventions. RESULTS: This tutorial highlights practical strategies and interdisciplinary approaches to promote inclusive, accessible communication in mainstream educational settings using two interdisciplinary case studies (one child diagnosed with septo-optic dysplasia and optic nerve hypoplasia at 1 year of age, then a severe language disorder, intellectual disability, and autism spectrum disorder at 6 years, and the other diagnosed with suspected cerebral vision impairment and single-sided hearing loss at 2 years of age). CONCLUSIONS: Children with blindness and low vision benefit from speech-language pathologist (SLP) collaboration with their families and professionals (e.g., orientation and mobility specialists, physiotherapists, occupational therapists) to actively support optimal learning and engagement. SLPs can apply the ICF and ECC and insights from the case studies to inform assessment, goal setting, collaborative planning, and intervention.

Middle interhemispheric variant (MIH) of holoprosencephaly (HPE), also known as syntelencephaly, is a rare subtype of HPE characterized by abnormal midline connection of the posterior parts of the frontal lobes and the anterior parts of the parietal lobes with variable corpus callosum abnormalities. We report the case of a five-year-old girl with syntelencephaly presenting with a cleft lip and palate, developmental delay, cerebral palsy, and intermittent diabetes insipidus. Brain magnetic resonance imaging demonstrated the characteristic features of both syntelencephaly and septo-optic dysplasia, including midline fusion of the frontal and parietal lobes, partial agenesis of the corpus callosum with hypoplastic genu and splenium, absence of the septum pellucidum, and bilateral optic nerve hypoplasia. Additional radiologic findings included bilateral subependymal gray matter heterotopia, colpocephaly, and an azygos anterior cerebral artery. A literature search was conducted on PubMed and Google Scholar, with combinations of "middle interhemispheric variant" or "syntelencephaly" and "septo-optic dysplasia," "pituitary gland dysfunction," "endocrine dysfunction," or "optic nerve hypoplasia." To the best of our knowledge, this represents the first published case of MIH-variant HPE associated with all three criteria for septo-optic dysplasia, expanding the known phenotypic spectrum of these rare malformations. The co-occurrence of syntelencephaly and septo-optic dysplasia in this patient may reflect a shared disruption of midline forebrain development during the fourth to eighth weeks of gestation, when interhemispheric cleavage and hypothalamic-pituitary-optic development overlap temporally and depend on interconnected signaling pathways, including SHH, ZIC2, and the SOX family of transcription factors. Recognition of this association may prompt clinicians to evaluate patients with MIH variant HPE for features of septo-optic dysplasia, including optic nerve abnormalities and hypothalamic-pituitary dysfunction, and highlights the need for interdisciplinary clinical management and long-term surveillance in these patients.

TUBB2B encodes a β-tubulin isotype essential for neuronal proliferation, migration, and organization during brain development. Pathogenic heterozygous variants in TUBB2B are associated with neurodevelopmental disorders including polymicrogyria and corpus callosum abnormalities. However, the phenotypic spectrum remains heterogeneous, most likely reflecting variant-specific effects on microtubule formation and stability. Homozygous TUBB2B variants are exceedingly rare, with one family reported to date. We describe five individuals in four families with rare TUBB2B variants. Four variants are described, including a previously reported de novo missense variant, c.292G>A (GenBank: NM_178012.5) (p.Gly98Arg), with potential phenotypic expansion including panhypopituitarism; a previously reported de novo missense variant, c.605T>C (GenBank: NM_178012.5) (p.Ile202Thr), showing interindividual heterogeneity; a de novo missense variant, c.43C>A (GenBank: NM_178012.5) (p.Gln15Lys) at a polyamination site critical for microtubule stability; and a homozygous missense variant within a region of absence of heterozygosity in two siblings from consanguineous parents, c.145G>A (GenBank: NM_178012.5) (p.Val49Ile). Both individuals also carry a pathogenic homozygous truncating ALKBH8 variant c.1675del (GenBank: NM_138775.3) (p.Arg559Alafs∗56), representing a potential dual molecular diagnosis driving clinical features reflective of contributions from both genes. These reports expand the clinical spectrum of TUBB2B-related tubulinopathies, illustrate phenotypic heterogeneity, and provide insights into disease mechanisms including effects at polyamination sites and rare recessive inheritance, underscoring the need for nuanced genotype-phenotype interpretation in diagnostic and counseling contexts.