Optic nerve hypoplasia
Encyclopedia
Optic nerve hypoplasia
(ONH) is a medical condition arising from the underdevelopment of the optic nerve
(s). This condition is the most common congenital optic nerve
anomaly. The optic disc
appears abnormally small, because not all the optic nerve axon
s have developed properly. It is often associated with endocrinopathies (hormone deficiencies), developmental delay, and brain malformations. The optic nerve, which is responsible for transmitting visual signals from the retina to the brain, has approximately 1.2 million nerve fibers in the average person. In those diagnosed with ONH, however, there are noticeably fewer nerve fibers, which range in number from patient to patient.
, absence of the septum pellucidum
, maldevelopment of the anterior and posterior pituitary gland
, and anomalies of the hypothalamus
. Because of this, all children with ONH are at risk for developmental delays and hormonal deficiencies, regardless of severity of ONH, or whether abnormalities are visible by MRI.
The incidence of ONH is increasing, although it is difficult to estimate the true prevalence. Between 1980 and 1999, the occurrences of ONH in Sweden increased four-fold to 7.2 per 100,000, while all other causes of childhood blindness had declined. In 1997, ONH overtook retinopathy of prematurity
as the single leading cause of infant blindness in Sweden, with 6.3 in every 100,000 births diagnosed with ONH. The most recent prevalence report out of England in 2006 is 10.9 per 100,000.
ONH impacts all ethnic groups, although in the United States, occurrence is lower in persons of Asian descent. To date, there have been few reports of ONH occurrence in Asian countries, although it is uncertain why this is so.
Children diagnosed with ONH generally present with vision problems which include nystagmus
(involuntary movement of the eyes), which tends to develop at 1 to 3 months and/or strabismus
(inability to align both eyes simultaneously), manifested during the first year of life.
The majority of children affected experience improvement in vision during the first few years of life, though the reason for this occurrence is unknown. There have been no reported cases of decline in vision due to ONH.
of the corpus callosum
, absence or incomplete development of the septum pellucidum
, malformations of the pituitary gland, schizencephaly
, cortical heterotopia
, white matter
hypoplasia, pachygyria
, and holoprosencephaly
. Hypoplasia of the corpus callosum, often in conjunction with other major malformations, is significantly associated with poor and delayed developmental outcome.
ONH is often referred to as septo-optic dysplasia, a term that refers to agenesis of the septum pellucidum. It is now clear that the absence of the septum pellucidum does not correlate with the associated symptoms of ONH.
(70%), hypothyroidism
(43%), adrenal insufficiency
(27%), and diabetes insipidus
(5%).
Absence of GH may often be indicated by short stature, although this is not always the case. Other indicators of GH deficiency may include hypoglycemic events (including seizures), prolonged jaundice, micropenis in boys, and delayed dentition
. Testing for GH may involve blood tests (IGF-1 and IGFBP-3), growth hormone stimulation test, or bone age x-ray of the hand or wrist (or body for children younger than 2 years).
A poorly functioning pituitary gland may also cause a lack of thyroid hormone, leading to central hypothyroidism. Thyroid hormone is critical for growth and brain development, especially during the first few weeks to months of life. Children with untreated hypothyroidism are at high risk of mental retardation; thus, early detection is crucial. Central hypothyroidism can be diagnosed by a low or normal thyroid-stimulating hormone (TSH) in the presence of a low level of free T4. Free T-4 should be checked annually for at least four years.
Cortisol
is made in times of stress. Approximately one-quarter of patients with ONH have adrenal insufficiency, meaning they do not produce enough cortisol on a daily basis or in stressful situations.
Imbalances in sex hormone may result in a delay in sexual development (puberty) or precocious puberty
. Sex hormones may be tested from birth to 6 months of age (during a mini-puberty).
Hyperprolactinemia (an excess of prolactin) often occurs in conjunction with ONH and indicates either dysfunction of the hypothalamus or a disconnect between the hypothalamus and pituitary gland. Hyperprolactinemia often correlates with development of obesity in children with ONH.
The posterior pituitary gland produces anti-diuretic hormone (ADH), which controls outflow of water from the body by urine. ADH deficiency, also known as diabetes insipidus (DI), results in dehydration and high sodium levels in the body from excessive urination. Testing for DI involves blood and urine testing, including water deprivation tests, to determine ADH creation levels by the body. DI may be treated with a medication called desmopressin acetate (DDAVP).
Oxtocin is also produced in the posterior pituitary gland. Though best known for its role in childbirth and lactation, oxytocin has also been found to have a role in human bonding, increase in trust, and decrease in fear.
Hypothalamic dysfunction may also result in problems with feeding, sleep, and body temperature regulation. Feeding behaviors in children with ONH often include hyperphagia (overeating), resulting in obesity; or hypophagia (reduced food intake) with or without weight loss. Children also frequently experience aversion to specific textures of food. Disturbance of circadian sleep rhythm
, resulting in abnormal sleep-wake cycles, is noted in one-third of children with ONH. This disturbance could result in behavioral problems and disruption of family life.
for hypopituitarism, occupational
, physical, and/or speech therapy for other issues, and services of a teacher of visually impaired students. Special attention should be paid to early development of oral motor skills and acclimation to textured foods for children with texture aversion, or who are otherwise resistant to eating.
Sleep dysfunction can be ameliorated using melatonin in the evening in order to adjust a child's circadian clock.
Treatment for strabismus may include patching of the better eye, which may result in improved vision in the worse eye; however, this should be reserved for cases in which the potential for vision improvement in both eyes is felt to be good. Surgery to align the eyes can be performed once children with strabismus develop equal visual acuity in both eyes, most often after the age of three. Generally surgery results in improved appearance only and not in improved visual function.
. Although most patients with only optic nerve involvement lead normally productive lives, those with accompanying endocrine dysfunction or other midline cerebral abnormalities are more at risk for on-going intellectual and other disabilities.
Hypoplasia
Hypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia...
(ONH) is a medical condition arising from the underdevelopment of the optic nerve
Optic nerve
The optic nerve, also called cranial nerve 2, transmits visual information from the retina to the brain. Derived from the embryonic retinal ganglion cell, a diverticulum located in the diencephalon, the optic nerve doesn't regenerate after transection.-Anatomy:The optic nerve is the second of...
(s). This condition is the most common congenital optic nerve
Optic nerve
The optic nerve, also called cranial nerve 2, transmits visual information from the retina to the brain. Derived from the embryonic retinal ganglion cell, a diverticulum located in the diencephalon, the optic nerve doesn't regenerate after transection.-Anatomy:The optic nerve is the second of...
anomaly. The optic disc
Optic disc
The optic disc or optic nerve head is the location where ganglion cell axons exit the eye to form the optic nerve. There are no light sensitive rods or cones to respond to a light stimulus at this point. This causes a break in the visual field called "the blind spot" or the "physiological blind spot"...
appears abnormally small, because not all the optic nerve axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s have developed properly. It is often associated with endocrinopathies (hormone deficiencies), developmental delay, and brain malformations. The optic nerve, which is responsible for transmitting visual signals from the retina to the brain, has approximately 1.2 million nerve fibers in the average person. In those diagnosed with ONH, however, there are noticeably fewer nerve fibers, which range in number from patient to patient.
History and Epidemiology
ONH, also known as de Morsier’s Syndrome or septo-optic dysplasia, is a condition that can involve multiple problems in the midline structures of the brain, stemming from miswiring of the brain and central nervous system. Besides having small optic nerves, persons with ONH can have agenesis of the corpus callosumCorpus callosum
The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...
, absence of the septum pellucidum
Septum pellucidum
The septum pellucidum , and not to be confused with the medial septum, is a thin, triangular, vertical membrane separating the anterior horns of the left and right lateral ventricles of the brain...
, maldevelopment of the anterior and posterior pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
, and anomalies of the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
. Because of this, all children with ONH are at risk for developmental delays and hormonal deficiencies, regardless of severity of ONH, or whether abnormalities are visible by MRI.
The incidence of ONH is increasing, although it is difficult to estimate the true prevalence. Between 1980 and 1999, the occurrences of ONH in Sweden increased four-fold to 7.2 per 100,000, while all other causes of childhood blindness had declined. In 1997, ONH overtook retinopathy of prematurity
Retinopathy of prematurity
Retinopathy of prematurity , previously known as retrolental fibroplasia , is an eye disease that affects prematurely-born babies. It is thought to be caused by disorganized growth of retinal blood vessels which may result in scarring and retinal detachment. ROP can be mild and may resolve...
as the single leading cause of infant blindness in Sweden, with 6.3 in every 100,000 births diagnosed with ONH. The most recent prevalence report out of England in 2006 is 10.9 per 100,000.
Genetic risks
A specific genetic cause has not been found to explain the majority of cases of ONH.ONH impacts all ethnic groups, although in the United States, occurrence is lower in persons of Asian descent. To date, there have been few reports of ONH occurrence in Asian countries, although it is uncertain why this is so.
Gestational and exposure history
Although many perinatal and prenatal risk factors for ONH have been suggested, the predominant, enduring, most frequent risk factors are young maternal age and primiparity (the affected child being the first child born to the mother). Increased frequency of delivery by caesarean section and fetal/neonatal complications, preterm labor, gestational vaginal bleeding, low maternal weight gain, and weight loss during pregnancy are also associated with ONH.Symptoms
ONH may be found in isolation or in conjunction with a myriad of functional and anatomic abnormalities of the central nervous system. Nearly 80% of those affected with ONH will experience hypothalamic dysfunction and/or impaired development of the brain, regardless of MRI findings or severity of ONH.Vision
ONH can be unilateral (in one eye) or bilateral (in both eyes), although it presents most often bilaterally (80%). Because the unilateral cases tend to have better vision, they are typically diagnosed at a later age than those with bilateral ONH. Visual acuity can range from no light perception to near-normal vision.Children diagnosed with ONH generally present with vision problems which include nystagmus
Nystagmus
Nystagmus is a condition of involuntary eye movement, acquired in infancy or later in life, that may result in reduced or limited vision.There are two key forms of Nystagmus: pathological and physiological, with variations within each type. Nystagmus may be caused by congenital disorders,...
(involuntary movement of the eyes), which tends to develop at 1 to 3 months and/or strabismus
Strabismus
Strabismus is a condition in which the eyes are not properly aligned with each other. It typically involves a lack of coordination between the extraocular muscles, which prevents bringing the gaze of each eye to the same point in space and preventing proper binocular vision, which may adversely...
(inability to align both eyes simultaneously), manifested during the first year of life.
The majority of children affected experience improvement in vision during the first few years of life, though the reason for this occurrence is unknown. There have been no reported cases of decline in vision due to ONH.
Neuroradiographic Abnormalities
Estimates of cerebral malformations vary from 39% to 90% of children with ONH. Abnormalities evident via neuroradiography can include agenesis (absence) or hypoplasiaHypoplasia
Hypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia...
of the corpus callosum
Corpus callosum
The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...
, absence or incomplete development of the septum pellucidum
Septum pellucidum
The septum pellucidum , and not to be confused with the medial septum, is a thin, triangular, vertical membrane separating the anterior horns of the left and right lateral ventricles of the brain...
, malformations of the pituitary gland, schizencephaly
Schizencephaly
Schizencephaly is a rare grey matter malformation of the brain. It belongs to the group of malformations of the central nervous system.-Presentation:...
, cortical heterotopia
Heterotopia
Heterotopia may refer to:* Heterotopia , the displacement of an organ from its normal position* Heterotopia , a concept of "other spaces" created by the philosopher Michel Foucault...
, white matter
White matter
White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
hypoplasia, pachygyria
Pachygyria
Pachygyria is a congenital malformation of the cerebral hemisphere. It results in unusually thick convolutions of the cerebral cortex. Typically, children have developmental delay and seizures, the onset and severity depending on the severity of the cortical malformation...
, and holoprosencephaly
Holoprosencephaly
Holoprosencephaly is a cephalic disorder in which the prosencephalon fails to develop into two hemispheres. Normally, the forebrain is formed and the face begins to develop in the fifth and sixth weeks of human pregnancy...
. Hypoplasia of the corpus callosum, often in conjunction with other major malformations, is significantly associated with poor and delayed developmental outcome.
ONH is often referred to as septo-optic dysplasia, a term that refers to agenesis of the septum pellucidum. It is now clear that the absence of the septum pellucidum does not correlate with the associated symptoms of ONH.
Hypothalamic Dysfunction
Dysfunction of the hypothalamus results in loss of regulation over behavior and function of the pituitary gland (master gland). Hypopituitarism is present in 75% to 80% of patients with ONH. The anterior pituitary gland contributes to growth, metabolism, and sexual development. The most common pituitary endocrinopathies are growth hormone (GH) deficiencyGrowth hormone deficiency
Growth hormone deficiency is a medical condition in which the body does not produce enough growth hormone . Growth hormone, also called somatotropin, is a polypeptide hormone which stimulates growth and cell reproduction...
(70%), hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
(43%), adrenal insufficiency
Adrenal insufficiency
Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...
(27%), and diabetes insipidus
Diabetes insipidus
Diabetes insipidus is a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine. There are several different types of DI, each with a different cause...
(5%).
Absence of GH may often be indicated by short stature, although this is not always the case. Other indicators of GH deficiency may include hypoglycemic events (including seizures), prolonged jaundice, micropenis in boys, and delayed dentition
Dentition
Dentition pertains to the development of teeth and their arrangement in the mouth. In particular, the characteristic arrangement, kind, and number of teeth in a given species at a given age...
. Testing for GH may involve blood tests (IGF-1 and IGFBP-3), growth hormone stimulation test, or bone age x-ray of the hand or wrist (or body for children younger than 2 years).
A poorly functioning pituitary gland may also cause a lack of thyroid hormone, leading to central hypothyroidism. Thyroid hormone is critical for growth and brain development, especially during the first few weeks to months of life. Children with untreated hypothyroidism are at high risk of mental retardation; thus, early detection is crucial. Central hypothyroidism can be diagnosed by a low or normal thyroid-stimulating hormone (TSH) in the presence of a low level of free T4. Free T-4 should be checked annually for at least four years.
Cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
is made in times of stress. Approximately one-quarter of patients with ONH have adrenal insufficiency, meaning they do not produce enough cortisol on a daily basis or in stressful situations.
Imbalances in sex hormone may result in a delay in sexual development (puberty) or precocious puberty
Precocious puberty
As a medical term, precocious puberty describes puberty occurring at an unusually early age. In most of these children, the process is normal in every respect except the unusually early age, and simply represents a variation of normal development. In a minority of children, the early development is...
. Sex hormones may be tested from birth to 6 months of age (during a mini-puberty).
Hyperprolactinemia (an excess of prolactin) often occurs in conjunction with ONH and indicates either dysfunction of the hypothalamus or a disconnect between the hypothalamus and pituitary gland. Hyperprolactinemia often correlates with development of obesity in children with ONH.
The posterior pituitary gland produces anti-diuretic hormone (ADH), which controls outflow of water from the body by urine. ADH deficiency, also known as diabetes insipidus (DI), results in dehydration and high sodium levels in the body from excessive urination. Testing for DI involves blood and urine testing, including water deprivation tests, to determine ADH creation levels by the body. DI may be treated with a medication called desmopressin acetate (DDAVP).
Oxtocin is also produced in the posterior pituitary gland. Though best known for its role in childbirth and lactation, oxytocin has also been found to have a role in human bonding, increase in trust, and decrease in fear.
Hypothalamic dysfunction may also result in problems with feeding, sleep, and body temperature regulation. Feeding behaviors in children with ONH often include hyperphagia (overeating), resulting in obesity; or hypophagia (reduced food intake) with or without weight loss. Children also frequently experience aversion to specific textures of food. Disturbance of circadian sleep rhythm
Circadian rhythm
A circadian rhythm, popularly referred to as body clock, is an endogenously driven , roughly 24-hour cycle in biochemical, physiological, or behavioural processes. Circadian rhythms have been widely observed in plants, animals, fungi and cyanobacteria...
, resulting in abnormal sleep-wake cycles, is noted in one-third of children with ONH. This disturbance could result in behavioral problems and disruption of family life.
Development
More than 70% of children with ONH experience developmental delay, ranging from isolated focal defects to delay in all areas of development (global delay). Motor delay is most common (75%) and communication delay is least common (44%). Predictors of significantly delayed development include hypoplasia or agenesis of the corpus callosum and hypothyroidism. The absence of the septum pellucidum does not predict developmental delay. Delays may occur in unilateral (39%) as well as bilateral (78%) cases.Diagnosis
ONH is diagnosed by ophthalmoscopic examination. Patients with ONH exhibit an optic nerve that appears smaller than normal and different in appearance from small optic nerves caused by other eye conditions such as optic (nerve) atrophy.Treatment
There is no treatment for ONH; however, many therapeutic interventions exist for the care of its symptoms. These may include hormone replacement therapyHormone replacement therapy
Hormone replacement therapy may refer to:*Hormone replacement therapy *Hormone replacement therapy *Hormone replacement therapy *Androgen replacement therapy -See also:...
for hypopituitarism, occupational
Occupational therapy
Occupational therapy is a discipline that aims to promote health by enabling people to perform meaningful and purposeful activities. Occupational therapists work with individuals who suffer from a mentally, physically, developmentally, and/or emotionally disabling condition by utilizing treatments...
, physical, and/or speech therapy for other issues, and services of a teacher of visually impaired students. Special attention should be paid to early development of oral motor skills and acclimation to textured foods for children with texture aversion, or who are otherwise resistant to eating.
Sleep dysfunction can be ameliorated using melatonin in the evening in order to adjust a child's circadian clock.
Treatment for strabismus may include patching of the better eye, which may result in improved vision in the worse eye; however, this should be reserved for cases in which the potential for vision improvement in both eyes is felt to be good. Surgery to align the eyes can be performed once children with strabismus develop equal visual acuity in both eyes, most often after the age of three. Generally surgery results in improved appearance only and not in improved visual function.
Prognosis
The visual prognosis in optic nerve hypoplasia is quite variable. Occasionally, optic nerve hypoplasia may be compatible with near-normal vision; in other cases, one or both eyes may be functionally, or legally blindBlindness
Blindness is the condition of lacking visual perception due to physiological or neurological factors.Various scales have been developed to describe the extent of vision loss and define blindness...
. Although most patients with only optic nerve involvement lead normally productive lives, those with accompanying endocrine dysfunction or other midline cerebral abnormalities are more at risk for on-going intellectual and other disabilities.
External links
- ONH Facts
- More ONH Facts
- FOCUS Families - information, education, and support
- The One Small Voice Foundation