NORD gratefully acknowledges Mark S. Borchert, MD, Director, Eye Birth Defects and Eye Technology Institutes, The Vision Center, Children's Hospital Los Angeles, and Associate Professor, Keck School of Medicine, University of Southern California for assistance in the preparation of this report.
Optic nerve hypoplasia (ONH) is a congenital disorder characterized by underdevelopment (hypoplasia) of the optic nerves. The optic nerves transmit impulses from the nerve-rich membranes lining the retina of the eye to the brain. Most people with ONH have abnormal eye movements (nystagmus) and vision can range from no light perception to good functional vision, or even full vision in one eye.
Children with ONH may have brain malformations and pituitary problems. Abnormalities of structures of the brain may include hypoplasia of the corpus callosum (nerve fibers that connect the two hemispheres of the brain), underdeveloped nerve fibers (white matter) in any other location, and abnormal migration of neurons to the surface of the brain (cortical heterotopia). The common association of absence of the septum pellucidum has no known functional consequence, and may occur with or without other brain malformations. The hypothalamus at the base of the brain is frequently abnormal. This is not usually visible on MRI scan. However, in the majority of patients, this results in abnormal function of the pituitary gland because of its control over the pituitary.Only a minority of affected individuals have visible neuroradiographic abnormalities of the pituitary gland. The pituitary gland is a hormone-producing gland at the base of the brain that controls hormones in the body that are necessary for growth, energy, and sexual development.
Some affected children have normal intelligence and others have learning disabilities and developmental delays. Deficiencies of certain hormones may result in growth retardation, poor development, and may be life-threatening without treatment. Hormone deficiencies can be controlled with daily hormone replacement therapy and close monitoring by an endocrinologist (hormone doctor). Approximately 10% of children diagnosed with ONH prior to age 2 years have no pituitary problems and normal MRI scans of the brain. Those children are still at risk for developmental delays.
The cause of ONH is not understood.
Optic nerve hypoplasia is the unifying feature of a spectrum condition, commonly known as septo-optic dysplasia (SOD) or DeMorsier syndrome, which includes hypopituitarism and absence of the septum pellucidum on MRI scan. The terms SOD and DeMorsier syndrome have fallen into disfavor because of recognition that absence of the septum pellucidum, which occurs in 1/3 of patients, has no clinically predictive value. In addition, DeMorsier was not describing this syndrome when he coined the term, septo-optic dysplasia.
ONH is present at birth, but many symptoms may not be apparent until childhood, or even adolescence. Most infants with ONH have involuntary, rapid eye movements (nystagmus) and/or mild to severe visual impairment of one or both eyes. Vision often improves modestly in early childhood even though there is no growth of the optic nerves after birth. Due to underdevelopment of the optic nerves, the optic disk is smaller than normal size in one or both eyes when viewed by a doctor using an ophthalmoscope. Also referred to as the “blind spot,” the optic disk is the structure in which nerve fibers from the retina combine to form the optic nerve before leaving the back of the eye. The optic nerves meet to form the optic chiasm and optic tracts at the base of the hypothalamus.
Affected individuals may also exhibit symptoms due to underdevelopment of the hypothalamus at the base of the brain. The hypothalamus is divided into several different regions that have different functions. The hypothalamus is responsible for regulating basic body functions such as thirst, hunger, sleep, and body temperature. As a result, children with ONH frequently have problems with these functions. Although the hypothalamus is commonly abnormal in individuals with ONH, the abnormalities are rarely visible on MRI scans.
The hypothalamus also coordinates the function of the pituitary gland by controlling the gland’s release of certain hormones. The pituitary gland, a small structure beneath the hypothalamus produces several hormones and releases them directly into the bloodstream. It is located directly below the optic nerves and is connected to the hypothalamus by a short stalk of nerve fibers and blood vessels. In most individuals with ONH, the hypothalamus does not communicate with the pituitary gland properly, resulting in a failure of the pituitary gland to produce or release the normal levels of certain hormones into the bloodstream.
The specific hormones that are affected and the severity of such hormone deficiencies may vary greatly from person to person. The majority of affected individuals lack sufficient levels of growth hormone (GH), which stimulates normal growth and development. Growth hormone deficiency is usually apparent before 6 years of age, when there is a decline in the normal growth rate that may ultimately result in short stature and other maturation delays.
Some individuals with ONH also have abnormally low levels of several other hormones such as adrenocorticotropic hormone (ACTH), which stimulates the adrenal gland to release corticosteroids to maintain blood sugar and blood pressure during times of physical or emotional stress. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH), from the pituitary play a role in coordinating the function of the male and female sexual organs and are essential for normal sexual development. Thyroid stimulating hormone (TSH) stimulates the thyroid gland to release thyroid hormones, which is responsible for energy metabolism. Absence of this hormone during infancy results in intellectual disability. The pituitary also releases antidiuretic hormone (ADH), which controls salt levels in the body by controlling urine output. Deficiencies in these hormone deficiencies may result in: intellectual disability; obesity; delayed sexual maturation; low levels of glucose in the blood (hypoglycemia); seizures; diabetes insipidus, a disorder characterized by excessive excretion of urine and excessive thirst. (For more information on hypothyroidism, hypoglycemia and diabetes insipidus, please see the Related Disorders section of this report.)
Other structures within the brain may also develop improperly. As a result, such brain structures may be absent, incompletely developed (hypoplastic), and/or malformed (dysplastic). For example, individuals with ONH frequently do not have the membrane (septum pellucidum) that normally separates the fluid-filled cavities (lateral ventricles) in both sides of the brain. Absence of the septum pellucidum does not cause any known problems and most commonly occurs in otherwise normal individuals. In many people with ONH, the thick band of nerve fibers that connects the left and right hemispheres of the brain (corpus callosum) is underdeveloped or absent. Such individuals are at increased risk for cognitive or developmental delay.
Many people with ONH may exhibit additional abnormalities. Delays in the acquisition of skills that require the coordination of mental and muscular activity (psychomotor retardation) are common in infants. Some affected children have normal intelligence and others have learning disabilities and intellectual disability. Autism is frequently diagnosed in children with ONH.
The cause of ONH is not known. In most cases, the disorder appears to occur randomly for unknown reasons (sporadic). Rare families have been reported with more than one affected child, suggesting the possibility of autosomal recessive inheritance. A few cases of “SOD” have been reported to result from a mutation HESX1, SOX2, SOX3, OTX2 or PROKR2 genes. The diagnosis of SOD has been loosely defined in these cases, with the majority having normal optic nerves or ocular malformations other than ONH. The vast majority of individuals with ONH do not have mutations in any of these genes, suggesting that other genes and/or environmental factors are involved in the development of this condition.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
ONH is thought to affect males and females in equal numbers. The prevalence is estimated to be 1 in 10,000 children.
ONH is diagnosed by a complete ophthalmologic examination. Imaging studies such as magnetic resonance imaging (MRI) and computerized tomography (CT) are used to examine the corpus callosum and optic nerves. ONH may be suspected, but not diagnosed, based on MRI findings, as other abnormalities can mimic the MRI findings of ONH. Abnormal levels of serum cortisol and growth hormone help to confirm the diagnosis.
The treatment of ONH is directed toward the specific symptoms in each individual. Treatment may require the coordinated efforts of a team of specialists including pediatricians, ophthalmologists, neurologists, endocrinologists and/or other health care professionals.
Specific therapies for ONH are symptomatic and supportive. Hormone deficiencies are treated with hormone replacement therapy. The vision abnormalities are usually not treatable.
Developmental testing should be performed to determine if deficiencies are present in gross or fine motor skills or in intelligence. Early intervention is important to ensure that children with ONH reach their potential. Special services that may be beneficial to affected children may include vision therapy, physical therapy, and occupational therapy.
Genetic counseling may be beneficial for affected children and their families.
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Contact for additional information about optic nerve hypoplasia:
Mark S. Borchert, MD
The Vision Center at Children’s Hospital Los Angeles
4650 Sunset Blvd, MS #88
Los Angeles, CA 90027
Email: [email protected]
Phone: (323) 361-6219
Thomas P. Septooptic Dysplasia. In: The NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott, Williams and Wilkins; 2003:188.
Garcia-Filion P, Almarzouki H, Fink C, Geffner M, Nelson M, Borchert M. Brain malformations do not predict hypopituitarism in young children with optic nerve hypoplasia.Horm Res Paediatr. 2017;88(3-4):251-257. https://www.ncbi.nlm.nih.gov/pubmed/28848142
Ryabets-Lienhard A, Stewart C, Borchert M, Geffner ME. The optic nerve hypoplasia spectrum: review of the literature and clinical guidelines. Advances in Pediatrics. 2016; 63:128-142.
Garcia-Filion P, Borchert M, Prenatal determinants of optic nerve hypoplasia: Review of suggested correlates and future focus. Surv Ophthalmol. 2013; 58:610-9.
Borchert M. Reappraisal of the optic nerve hypoplasia syndrome. J Neuroophthalmol. 2012; 32:58-67.
McNay DE, Turton JP, Kelberman D, et al. HESX1 mutations are an uncommon cause of septooptic dysplasia and hypopituitarism. J Clin Endocrinol Metab. 2007;92:691-697.
Benner JD, Preslan, MW, Gratz E, et al. Septo-optic dysplasia in two siblings. Am J Opthal. 1990;109:632-637.
Hoyt We, Kaplan SL, Grumbach MM, et al. Septo-optic dysplasia and pituitary dwarfism. Lancet. 1970;1:893-894.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Septooptic Dysplasia. Entry No: 182230. Last Edited 08/31/2016. Available at: http://omim.org/entry/182230 Accessed November 20, 2017.
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