====== Optic Nerve Hypoplasia ====== * Abnormally small optic nerve head * Congenital decrease optic nerve fibers **Septo Optic Dysplasia** - any combination of optic nerve hypoplasia, pituitary gland hypoplasia and midline brain abnormalities =====Epidemology===== * One of leading causes of childhood blindness * Incidence * Olmstead County, MN- 2.4 per 100,000 children (0-19 years) or 1 in 2287 live births * Alaska, 1 per 1000 live births * Manitoba Canada- 1 in 1,875 live births or 53.3/100,000 children < 19 years old [[https://pubmed-ncbi-nlm-nih-gov.slhs.idm.oclc.org/29479262/|Paediatr Child Health 2017 Nov;22(8):445]] * Stockholm, Sweden- 17.3/100,000 children < 18 years old [[https://pubmed-ncbi-nlm-nih-gov.slhs.idm.oclc.org/24119069/|Acta Ophthalmol 2014 Sep;92(6):563]] =====Risk Factors===== * Young maternal age * First parity * Maternal smoking * Preterm birth =====Diagnosis===== ===Clinical Features=== * Peripapillary ring- "Double ring sign" * Small optic nerve * Thinning of the nerve fiber layer * Possible tortuosity of retinal vasculature * Possible persistent grey appearance of the nerve ===Optic Nerve Measurements=== * Fundus Photography * Ratio of Mean Disc Diameter (DD) to Macula-Disc distance (DM) * (Horizontal + Vertical Disc Diameter /2) : Distance from center of disc to the center of the macula * {{::dd-dm_ratio.png?600|DD:DM ratio measurements}}\\ from Dutton GN. Congenital Disorders of the optic nerve: excavations and hypoplasia. Eye.2004;18:1038-1048 * OPTOS photographs of 188 adults and children with OHN (108) compared to normals (88) * Normal optic nerve horizontal diameter: 1.70 mm (95% CI 1.49, 2.14) * Hypoplasia horizontal optic nerve diameter: 1.23 mm (95% CI 0.38, 1.45) * {{::direct_optos_nerve_size_in_optic_nerve_hypoplasia_in_alaska_2020.pdf |Arnold AW et al. Direct OPTOS Nerve Size Determination of Prevalent Optic Nerve Hypoplasia in Alaska. Clinical Ophthalmology 2020;14:491-499}} * Optical Coherence Tomography * Many commercial devices will attempt to plot the disc diameter and area * [[optic_nerve_diameter_calculator|Use this calculator to estimate the nerve diameter using the Heidelberg OCT machine optic nerve report without the glaucoma upgrade]] * MRI =====Genetics===== * 11 rare single nucleotide variants were identified in 10 persons (34%) in one 2020 study, including: * 2 variants in COL4A1 * 2 variants in COL4A2 * 2 variants in CYP26C1 * 1 variant in each of OPA1 (in a patient who also had a COL4A1 variant), KIF7, SPG7, CYP26A1, and UBE3B * 1 copy number variant was identified in SOX5 in 1 patient See [[https://pubmed-ncbi-nlm-nih-gov.slhs.idm.oclc.org/32040484/|PLoS One 2020;15(2):e0228622]] =====Associated Findings===== * Brain Anomalies * More common * Microcephly, absent septum pellucid, posterior pituitary ectopia, migrational anomalies (hypoplasia of corpus callous) * Less common * porencephaly, schizencephaly, arachnoid cyst, epidermoid cyst * Pituitary Dysfunction * neonatal hypoglycemia * associated with neonatal cholestatic jaundice, convulsions and or coma after anesthesia * growth hormone deficency * diabetes insipidus * olfactory hypoplasia ===In Olmstead County, MD population=== * Premature birth- 32% * Maternal diabetes- 16% * Bilateral- 84% * Developmental Delay- 63% * Neurologic defects- 53% * Microcephaly (16%) * Cerebral palsy (16%) * Corpus callous hypoplasia (11%) * Septum Pellucidum aplasia (11%) * White matter hypoplasia (11%) * Hydrocephalus (11%) * Decreased visual acuity- 47% * Strabismus- 42% * Esotropia 21% * Exotropia 21% * Endocrine dysfunction- 26% * Growth hormone deficiency (16%) * Hypothyroid (16%) * Diabetes insipidus (11%) * Adrenal insufficiency (5%) * Hypopituitarism (5%) * Precocious puberty (5%) * Nystagmus- 26% * Refractive error can be myopia, hyperopia and or astigmatism * Amblyopia- 11% ====Associated Disorders==== * [[aicardi_syndrome|Aicardi Syndrome]] * [[charge_syndrome|CHARGE Syndrome]] * Dominant inheritance * Prenatal Drug exposure * Anticonvulsants * [[https://en.wikipedia.org/wiki/Phenytoin|Phenytoin (dilantin)]] * [[https://en.wikipedia.org/wiki/Phenobarbital|Phenobarbital]] * Ethanol * [[https://en.wikipedia.org/wiki/Isotretinoin|Isotretinoin]] * [[https://en.wikipedia.org/wiki/Valproate|Valproic Acid]] * Chromosome abnormalities * Distal 5q deletion syndrome * Chromsome 1 anomaly- Muscle eye brain disease * Partial deletion chromosome 6p * Chromosome 7(q22→q34) and 7q32-34 interstitial duplication * Chromosome 17 interstitial deletion * Frontonasal dysplasia * [[goldenhar_syndrome|Goldenhar syndrome]] * Idiopathic growth hormone deficiency (ONH seen in 9%) * Nevus sebaceous of Jadassohn (cutaneous, possibly malignant, phacomatosis) * Maternal Diabetes * Orbital hemangioma * Periventricular leukomalacia * Suprasellar teratoma ======Resources====== * {{::incidence_and_associated_endocrine_and_neurologic_abnormalities_of_optic_nerve_hypoplasia_2013.pdf |Mohoney BG et al. Incidence and Associated Endocrine and Neurologic Abnormalities of Optic Nerve Hypoplasia. JAMA Ophthalmol. 2013:131(7)898-902. }} * {{:congentital_disorders_optic_nerve_excavations_copy.pdf|Dutton GN. Disorders of the optic nerve: excavations and hypoplasia.Eye 2004;18:1038-1048}} * {{::direct_optos_nerve_size_in_optic_nerve_hypoplasia_in_alaska_2020.pdf |Arnold AW et al. Direct OPTOS Nerve Size Determination of Prevalent Optic Nerve Hypoplasia in Alaska. Clinical Ophthalmology 2020;14:491-499}} * {{::comparison_of_heidelberg_retina_tomograph_with_disc-macula_distance_to_disc_2016.pdf |Pang Y. et al. Comparison of Heidelberg Retina Tomograph with disc macula distance to disc diameter ratio in diagnosing optic nerve hypoplasia}} * {{::clinical_and_morphologic_spectrum_of_optic_nerve_hypoplasia_1999.pdf |Hellström A. et al. The Clinical and Morphologic Spectrum of Optic Nerve Hypoplasia. JAAPOS 1999;3(4):212-20}}