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Optic Nerve Hypoplasia: More Than Meets the Eye
Journal of Pediatric Nursing xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Journal of Pediatric Nursing
PENS Department
Optic Nerve Hypoplasia: More Than Meets the Eye Irena Hozjan, MN, RN (EC), NP-Pediatrics ⁎ Endocrine Program, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
Optic nerve hypoplasia (ONH), a disorder of brain development characterized by underdevelopment of the optic nerves, is an increasingly common cause of congenital blindness and visual impairment with associated lifelong morbidity (Garcia-Filion & Borchert, 2013a). The prevalence of ONH is estimated at 1.73 per 10,000 children (Tear Fahnehjelm, Dahl, Martin, & Ek, 2014) with males and females equally affected. ONH represents a complex spectrum of brain neuroanatomic malformation with varied neurologic, neuroendocrine, cognitive, behavioral and developmental manifestations that challenge the multidisciplinary pediatric team to provide comprehensive and developmentally appropriate care and long-term health surveillance. Clinical Presentation ONH is present at birth, however, it may not become apparent until childhood or in rare cases adolescence. The clinical presentation of ONH in the neonatal period and throughout infancy may involve prolonged jaundice, hypoglycemia, micropenis or cryptorchidism, lethargy, poor feeding and failure to thrive, irritability, neurologic deficits, seizures, hypotonia, polyuria, vital sign instability including difficulties with temperature regulation, and central congenital (secondary) hypothyroidism (Ryabets-Lienhard, Stewart, Borchert, & Geffner, 2016). Beyond the neonatal period, most will have abnormal eye movements and all infants with poor visual behavior, strabismus, or nystagmus by 3 months of age should have an ophthalmoscopic examination to rule out ONH (Garcia-Filion & Borchert, 2013a). Nystagmus usually develops in the first 1 to 3 months in bilateral cases, and strabismus (often esotropia and/or amblyopia) in the first year of life in unilateral ONH. Diagnosis of ONH is primarily clinical. Direct ophthalmoscopic examination will confirm a small optic disc with pigmented ring or double ring and tortuous and/or unusually straight with decreased branching retinal vessels may be noted (Taylor, 2007). ONH tends to be largely bilateral though has been reported to be unilateral in 15– 25% of cases (Garcia et al., 2006). Visual Effects Visual impairment in ONH is considered non-progressive, and there has been documentation of improvement in vision in the first years of ⁎ Corresponding author: Irena Hozjan. E-mail address: [email protected].
life (Fink et al., 2012; Garcia-Filion & Borchert, 2013a) with maturation of the visual pathways. Visual disturbances may be either unilateral or bilateral, and may range from mild, moderate to severe with visual acuity ranging from near normal functional vision to no light perception complete blindness. More than 80% of bilateral cases are legally blind with central visual acuity of 20/200 or less (Siatkowski, Sanchez, Andrade, & Alvarez, 1997). Other visual issues include photophobia (mild to severe), limitations in peripheral vision and alterations in depth perception that is more severe if vision loss is significant (Kaur, Jain, Sodhi, Rastogi, & Kamlesh, 2013). Minor visual field deficits may lead to a late diagnosis of ONH in those with normal visual acuity. Children should be monitored by a neurophthalmologist or ophthalmologist regularly for amblyopia and refractive errors.
Causes of ONH The cause of ONH is not completely understood. OHN develops during a vulnerable time of embryogenesis and early fetal development in the first months of gestation when the pituitary and optic nerve areas are under active development. Numerous retrospective and prospective studies have consistently reported young maternal age and primiparity as independent and predominant prenatal risk factors associated with OHN (Atapattu et al., 2012; Garcia-Filion & Borchert, 2013b; Garcia-Filion, Fink, Geffner, & Borchert, 2010). Genetic and familial case reports of ONH are rare. The majority of cases are sporadic and of unknown cause.
Neuroanatomical Effects Neuroanatomical abnormalities on MRI are frequent and hypoplasia of the corpus callosum with or without an absent septum pellucidum is a common malformation (Ahmad et al., 2006; Garcia-Filion & Borchert, 2013a; Garcia-Filion et al., 2010). Schizencephaly, polymicrogyria and hydrocephalus are some other major neuroanatomical abnormalities identified with concomitant neurological deficits, seizures, behavioral abnormalities, and developmental delay. Pituitary abnormalities may include ectopic posterior pituitary, empty sella and absence of the pituitary infundibulum and lack of posterior pituitary bright spot (Phillips, Spear, & Brodsky, 2001). Those with severe brain malformations, hydrocephalus, seizures and/or neurological deficits should be monitored by a neurologist and/or neurosurgeon (Borchert, 2012).
http://dx.doi.org/10.1016/j.pedn.2017.03.011 0882-5963/© 2017 Elsevier Inc. All rights reserved.
Please cite this article as: Hozjan, I., Optic Nerve Hypoplasia: More Than Meets the Eye, Journal of Pediatric Nursing (2017), http://dx.doi.org/ 10.1016/j.pedn.2017.03.011
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I. Hozjan / Journal of Pediatric Nursing xxx (2017) xxx–xxx
Septo-Optic Dysplasia Septo-optic dysplasia (SOD) is a clinical diagnosis, and has traditionally been made with the presence of two or more features of the classic triad of (1) optic nerve hypoplasia, either unilateral or bilateral, (2) midline brain defects including hypoplasia or absence of the septum pellucidum or corpus callosum, and (3) pituitary hormone deficiencies resulting in isolated to multiple hormone deficiencies (Kelberman & Dattani, 2008). However, the absence of a septum pellucidum or other midline malformations is not prognostic of hypothalamic–pituitary abnormalities, and ONH alone is an independent risk factor for hypothalamic–pituitary dysfunction in approximately 60–80 percent of cases (Ryabets-Lienhard et al., 2016). Neuroendocrine Effects Hypothalamic dysfunction and pituitary deficiencies are the most common source of nonvisual morbidity in ONH, and disruptions in hypothalamic homeostatic mechanisms impact pituitary gland function, temperature regulation, hunger behaviors (hyperphagia/hypophagia), thirst, and sleep–wake cycles (Garcia-Filion & Borchert, 2013a). There is correlation between severity of visual impairment and developmental delay to hypothalamic pituitary dysfunction (Rivkees, Fink, Nelson, & Borchert, 2010). Hyperprolactinemia is a marker for hypothalamic dysfunction (Vedin, Garcia-Filion, Fink, Borchert, & Geffner, 2012) and increases risk of other pituitary deficiencies. Overweight and obesity related to hypothalamic dysfunction and hyperphagia in ONH predisposes these children to lifelong morbidity (Ahmad et al., 2006). Hypopituitarism in ONH is a widely recognized clinical association and a lack of pituitary findings on imaging does not preclude the development of hypopituitarism in ONH (Ahmad et al., 2006). While pituitary deficiencies may occur at any age, the majority of children will experience one or more abnormality by age five years (Ahmad et al., 2006; Garcia-Filion et al., 2008; Oatman, McClellan, Olson, & Garcia-Filion, 2015; Vedin et al., 2012). Regular endocrine monitoring and follow-up is required. Growth hormone deficiency (GHD) is the most common deficiency in ONH and may present in infancy or evolve during childhood (Garcia-Filion et al., 2008; Haddad & Eugster, 2005; Oatman et al., 2015). Children with ONH require ongoing assessment of linear growth with evaluation of their growth hormone axis (IGF-1, IGFBP-3) with provocative growth hormone testing when levels are considered below reference range and/or linear growth slows. Central (secondary) hypothyroidism, the second most common pituitary deficiency in ONH (Ma, Fink, Geffner, & Borchert, 2010), may develop over time. Central congenital hypothyroidism may be missed on newborn screening (NBS) as initial thyroid stimulating hormone (TSH) testing is designed to test for congenital (primary) hypothyroidism with elevated TSH. Infants with ONH and central hypothyroidism have been shown to have lower TSH on NBS and were found to have significantly worse vision outcomes (Fink et al., 2012). Secondary adrenal insufficiency (AI) in ONH is a result of corticotropin-releasing hormone and/or adrenocorticotropic hormone (ACTH) deficiency. Infants and children should have repeated morning cortisol measurements and/or provocative ACTH stimulation testing for low random or morning cortisol levels. Those patients with a low or inadequate cortisol response will require daily oral glucocorticoids for maintenance and oral or injectable intramuscular glucocorticoid for stress dosing during illness or significant physical stress. Children with ONH are at risk of sudden death (Brodsky, Conte, Taylor, Hoyt, & Mrak, 1997; Donahue, Lavina, & Najjar, 2005) related to AI and diabetes insipidus. Diabetes insipidus (DI) as a result of deficiency of posterior pituitary gland derived anti-diuretic hormone tends to be less common (Djermane et al., 2016) though its presence may increase morbidity. DI may be challenging to evaluate in an infant or child. Classic findings
include polyuria, polydipsia, enuresis, dehydration, and symptoms of hypernatremia (restlessness, irritability, nausea, vomiting, lethargy, seizures and muscular twitching). Pubertal disturbances are common and may include absent, delayed, precocious and rapid tempo variations once started (Oatman et al., 2015). It is not uncommon to observe and manage precocious and/or rapid tempo pubertal development with gonadotropin-releasing hormone agonists in a young child who has isolated GHD and/or additional pituitary deficiencies. Evaluation of the hypothalamic–pituitary–gonadal axis (luteinizing hormone, follicle stimulating hormone, and estradiol in females or testosterone in males) may be completed early in the first 6 months of life during the transient phase of mini-puberty in infancy to identify possible hypothalamic hypogonadism concerns for the future. Otherwise, evaluation of precocious or delayed puberty is undertaken. Developmental Effects Developmental delay is a finding in a majority of patients with hypoplasia of the corpus callosum and hypothyroidism in either unilateral or bilateral ONH (Garcia-Filion et al., 2008) and may range from mild delays to significant and/or profound global delays. Autism spectrum disorder (ASD) is common in the visually impaired population, particularly among the profoundly visually impaired. ASD is highly prevalent in children with ONH (Garcia-Filion & Borchert, 2013a). Some behaviors and mannerisms that overlap in ASD and ONH include echolalia, pronoun reversals, stereotypic motor movements such as eye rubbing, hand movements (flapping, posturing), delays or limits in imaginative play, and atypical touching, smelling or exploration of new or foreign objects (Brown, Hobson, Lee, & Stevenson, 1997). As children with ONH develop and become more comfortable exploring and moving around their environments, their reciprocal social and communication behaviors improve and their repetitive behaviors and mannerisms may decrease. Diagnoses of ASD in very young children with vision impairment may not persist over time (Hobson & Lee, 2010; Williams, Fink, Zamora, & Borchert, 2014). Nursing and Team Considerations An individualized family-centered, multidisciplinary pediatric team approach is required to provide medically complex care and longterm surveillance. The pediatric nurse will provide the child and family with ongoing education, anticipatory guidance, and emotional support. The nurse will recommend and support appropriate strategies for optimal therapy adherence and pain management for necessary injections. The nurse will provide reinforcement of stress dosing needs for glucocorticoids in AI and management of sick days in AI and/or DI. Emergency care plans will be provided for primary caregivers, extended family, and the child's school. The nurse will reinforce the importance of wearable medical alert documentation. Additionally, the nurse will facilitate the coordination of care and multidisciplinary services for each child and family and identify when additional evaluations and early interventions may be appropriate. Developmental evaluations and early intervention are important to ensure that children with ONH are supported to maximize their functional outcomes. Children should be referred to early intervention programs, tailored for visually impaired children, for evaluation and treatment of possible developmental deficits and therapeutic ancillary services. These services may include: occupational therapy for oral motor skills, oral defensiveness or aversions, and a focus on feeding; physical therapy for large muscle and gross motor skill development such as ambulation, orientation and mobility; speech-language services for delays in communication development; a dietician to address failure to thrive and weight management issues; social work to provide emotional support and connection to resources; behavioral therapy for the child with emotional and/or behavioral issues related to attention
Please cite this article as: Hozjan, I., Optic Nerve Hypoplasia: More Than Meets the Eye, Journal of Pediatric Nursing (2017), http://dx.doi.org/ 10.1016/j.pedn.2017.03.011
I. Hozjan / Journal of Pediatric Nursing xxx (2017) xxx–xxx
deficit disorder, ASD, or other neurological dysfunction; and a teacher for the visually impaired to optimize residual vision, orientation and mobilization and address harmful behaviors (e.g., eye pressing or poking). Children with ONH may qualify for special education under a number of categories including visual or cognitive impairment and/or multiple disabilities. Resources such as the MAGIC Foundation, support groups, and institutes or foundations for the blind will be beneficial for the child and family. In summary, the childhood challenges of ONH are complex and encompass a range of mild to profound neurodevelopmental and neurocognitive delays and disabilities, visual impairment, ASD, evolving hypopituitarism and obesity with concomitant risk for increased morbidity and mortality. Children with ONH require careful regular longterm multidisciplinary care, and follow up for medical management of ongoing growth and development, health surveillance, pituitary screening, developmental support, and anticipatory guidance. Acknowledgments Sincere thanks to Mark R. Palmert MD, PhD and Cheryl-Ann Ryans RN for their review and insight. References Ahmad, T., Garcia-Filion, P., Borchert, M., Kaufman, F., Burkett, L., & Geffner, M. (2006). Endocrinological and auxological abnormalities in young children with optic nerve hypoplasia: A prospective study. Journal of Pediatrics, 148, 78–84. http://dx.doi.org/ 10.1016/j.jpeds.2005.08.050. Atapattu, N., Ainsworth, J., Willshaw, H., Parulekar, M., MacPherson, L., Miller, C., ... Kirk, J. M. (2012). Septo-optic dysplasia: Antenatal risk factors and clinical features in a regional study. Hormone Research in Pædiatrics, 78, 81–87. http://dx.doi.org/10.1159/ 000341148. Borchert, M. (2012). Reappraisal of the optic nerve hypoplasia syndrome. Journal of Neuro-Ophthalmology, 32, 58–67. http://dx.doi.org/10.1097/WNO.0b013e31824442b8. Brodsky, M. C., Conte, F. A., Taylor, D., Hoyt, C. S., & Mrak, R. E. (1997). Sudden death in septo-optic dysplasia. Report of 5 cases. Archives of Ophthalmology, 115, 66–70. Brown, R., Hobson, R. P., Lee, A., & Stevenson, J. (1997). Are there "autistic-like" features in congenitally blind children? Journal of Child Psychology and Psychiatry and Allied Disciplines, 38, 693–703. Djermane, A., Elmaleh, M., Simon, D., Poidvin, A., Carel, J. C., & Leger, J. (2016). Central diabetes insipidus in infancy with or without hypothalamic adipsic hypernatremia syndrome: Early identification and outcome. Journal of Clinical Endocrinology and Metabolism, 101, 635–643. http://dx.doi.org/10.1210/jc.2015-3108. Donahue, S. P., Lavina, A., & Najjar, J. (2005). Infantile infection and diabetes insipidus in children with optic nerve hypoplasia. British Journal of Ophthalmology, 89, 1275–1277. http://dx.doi.org/10.1136/bjo.2005.069609. Fink, C., Vedin, A. M., Garcia-Filion, P., Ma, N. S., Geffner, M. E., & Borchert, M. (2012). Newborn thyroid-stimulating hormone in children with optic nerve hypoplasia: Associations with hypothyroidism and vision. Journal of AAPOS, 16, 418–423. http://dx.doi. org/10.1016/j.jaapos.2012.05.012.
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Garcia, M. L., Ty, E. B., Taban, M., David Rothner, A., Rogers, D., & Traboulsi, E. I. (2006). Systemic and ocular findings in 100 patients with optic nerve hypoplasia. Journal of Child Neurology, 21, 949–956. Garcia-Filion, P., & Borchert, M. (2013a). Optic nerve hypoplasia syndrome: A review of the epidemiology and clinical associations. Current Treatment Options in Neurology, 15, 78–89. http://dx.doi.org/10.1007/s11940-012-0209-2. Garcia-Filion, P., & Borchert, M. (2013b). Prenatal determinants of optic nerve hypoplasia: Review of suggested correlates and future focus. Survey of Ophthalmology, 58, 610–619. http://dx.doi.org/10.1016/j.survophthal.2013.02.004. Garcia-Filion, P., Epport, K., Nelson, M., Azen, C., Geffner, M. E., Fink, C., & Borchert, M. (2008). Neuroradiographic, endocrinologic, and ophthalmic correlates of adverse developmental outcomes in children with optic nerve hypoplasia: A prospective study. Pediatrics, 121, e653–e659. http://dx.doi.org/10.1542/peds.2007-1825. Garcia-Filion, P., Fink, C., Geffner, M. E., & Borchert, M. (2010). Optic nerve hypoplasia in North America: A re-appraisal of perinatal risk factors. Acta Ophthalmologica, 88, 527–534. http://dx.doi.org/10.1111/j.1755-3768.2008.01450.x. Haddad, N. G., & Eugster, E. A. (2005). Hypopituitarism and neurodevelopmental abnormalities in relation to central nervous system structural defects in children with optic nerve hypoplasia. Journal of Pediatric Endocrinology and Metabolism, 18, 853–858. Hobson, R. P., & Lee, A. (2010). Reversible autism among congenitally blind children? A controlled follow-up study. Journal of Child Psychology and Psychiatry and Allied Disciplines, 51, 1235–1241. http://dx.doi.org/10.1111/j.1469-7610.2010.02274.x. Kaur, S., Jain, S., Sodhi, H. B., Rastogi, A., & Kamlesh (2013). Optic nerve hypoplasia. Oman Journal of Ophthalmology, 6, 77–82. http://dx.doi.org/10.4103/0974-620X.116622. Kelberman, D., & Dattani, M. T. (2008). Septo-optic dysplasia - Novel insights into the aetiology. Hormone Research, 69, 257–265. http://dx.doi.org/10.1159/000114856. Ma, N. S., Fink, C., Geffner, M. E., & Borchert, M. (2010). Evolving central hypothyroidism in children with optic nerve hypoplasia. Journal of Pediatric Endocrinology and Metabolism, 23, 53–58. Oatman, O. J., McClellan, D. R., Olson, M. L., & Garcia-Filion, P. (2015). Endocrine and pubertal disturbances in optic nerve hypoplasia, from infancy to adolescence. International Journal of Pediatric Endocrinology, 2015, 8. http://dx.doi.org/10.1186/ s13633-015-0005-3. Phillips, P. H., Spear, C., & Brodsky, M. C. (2001). Magnetic resonance diagnosis of congenital hypopituitarism in children with optic nerve hypoplasia. Journal of AAPOS, 5, 275–280. Rivkees, S. A., Fink, C., Nelson, M., & Borchert, M. (2010). Prevalence and risk factors for disrupted circadian rhythmicity in children with optic nerve hypoplasia. British Journal of Ophthalmology, 94, 1358–1362. http://dx.doi.org/10.1136/bjo.2009.175851. Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The optic nerve hypoplasia spectrum: Review of the literature and clinical guidelines. Advances in Pediatrics, 63, 127–146. http://dx.doi.org/10.1016/j.yapd.2016.04.009. Siatkowski, R. M., Sanchez, J. C., Andrade, R., & Alvarez, A. (1997). The clinical, neuroradiographic, and endocrinologic profile of patients with bilateral optic nerve hypoplasia. Ophthalmology, 104, 493–496. Taylor, D. (2007). Developmental abnormalities of the optic nerve and chiasm. Eye (London, England), 21, 1271–1284. http://dx.doi.org/10.1038/sj.eye.6702851. Tear Fahnehjelm, K., Dahl, S., Martin, L., & Ek, U. (2014). Optic nerve hypoplasia in children and adolescents; prevalence, ocular characteristics and behavioral problems. Acta Ophthalmologica, 92, 563–570. http://dx.doi.org/10.1111/aos.12270. Vedin, A. M., Garcia-Filion, P., Fink, C., Borchert, M., & Geffner, M. E. (2012). Serum prolactin concentrations in relation to hypopituitarism and obesity in children with optic nerve hypoplasia. Hormone Research in Pædiatrics, 77, 277–280. http://dx.doi.org/10. 1159/000338330. Williams, M. E., Fink, C., Zamora, I., & Borchert, M. (2014). Autism assessment in children with optic nerve hypoplasia and other vision impairments. Developmental Medicine and Child Neurology, 56, 66–72. http://dx.doi.org/10.1111/dmcn.12264.
Please cite this article as: Hozjan, I., Optic Nerve Hypoplasia: More Than Meets the Eye, Journal of Pediatric Nursing (2017), http://dx.doi.org/ 10.1016/j.pedn.2017.03.011
Contents lists available at ScienceDirect
Journal of Pediatric Nursing
PENS Department
Optic Nerve Hypoplasia: More Than Meets the Eye Irena Hozjan, MN, RN (EC), NP-Pediatrics ⁎ Endocrine Program, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
Optic nerve hypoplasia (ONH), a disorder of brain development characterized by underdevelopment of the optic nerves, is an increasingly common cause of congenital blindness and visual impairment with associated lifelong morbidity (Garcia-Filion & Borchert, 2013a). The prevalence of ONH is estimated at 1.73 per 10,000 children (Tear Fahnehjelm, Dahl, Martin, & Ek, 2014) with males and females equally affected. ONH represents a complex spectrum of brain neuroanatomic malformation with varied neurologic, neuroendocrine, cognitive, behavioral and developmental manifestations that challenge the multidisciplinary pediatric team to provide comprehensive and developmentally appropriate care and long-term health surveillance. Clinical Presentation ONH is present at birth, however, it may not become apparent until childhood or in rare cases adolescence. The clinical presentation of ONH in the neonatal period and throughout infancy may involve prolonged jaundice, hypoglycemia, micropenis or cryptorchidism, lethargy, poor feeding and failure to thrive, irritability, neurologic deficits, seizures, hypotonia, polyuria, vital sign instability including difficulties with temperature regulation, and central congenital (secondary) hypothyroidism (Ryabets-Lienhard, Stewart, Borchert, & Geffner, 2016). Beyond the neonatal period, most will have abnormal eye movements and all infants with poor visual behavior, strabismus, or nystagmus by 3 months of age should have an ophthalmoscopic examination to rule out ONH (Garcia-Filion & Borchert, 2013a). Nystagmus usually develops in the first 1 to 3 months in bilateral cases, and strabismus (often esotropia and/or amblyopia) in the first year of life in unilateral ONH. Diagnosis of ONH is primarily clinical. Direct ophthalmoscopic examination will confirm a small optic disc with pigmented ring or double ring and tortuous and/or unusually straight with decreased branching retinal vessels may be noted (Taylor, 2007). ONH tends to be largely bilateral though has been reported to be unilateral in 15– 25% of cases (Garcia et al., 2006). Visual Effects Visual impairment in ONH is considered non-progressive, and there has been documentation of improvement in vision in the first years of ⁎ Corresponding author: Irena Hozjan. E-mail address: [email protected].
life (Fink et al., 2012; Garcia-Filion & Borchert, 2013a) with maturation of the visual pathways. Visual disturbances may be either unilateral or bilateral, and may range from mild, moderate to severe with visual acuity ranging from near normal functional vision to no light perception complete blindness. More than 80% of bilateral cases are legally blind with central visual acuity of 20/200 or less (Siatkowski, Sanchez, Andrade, & Alvarez, 1997). Other visual issues include photophobia (mild to severe), limitations in peripheral vision and alterations in depth perception that is more severe if vision loss is significant (Kaur, Jain, Sodhi, Rastogi, & Kamlesh, 2013). Minor visual field deficits may lead to a late diagnosis of ONH in those with normal visual acuity. Children should be monitored by a neurophthalmologist or ophthalmologist regularly for amblyopia and refractive errors.
Causes of ONH The cause of ONH is not completely understood. OHN develops during a vulnerable time of embryogenesis and early fetal development in the first months of gestation when the pituitary and optic nerve areas are under active development. Numerous retrospective and prospective studies have consistently reported young maternal age and primiparity as independent and predominant prenatal risk factors associated with OHN (Atapattu et al., 2012; Garcia-Filion & Borchert, 2013b; Garcia-Filion, Fink, Geffner, & Borchert, 2010). Genetic and familial case reports of ONH are rare. The majority of cases are sporadic and of unknown cause.
Neuroanatomical Effects Neuroanatomical abnormalities on MRI are frequent and hypoplasia of the corpus callosum with or without an absent septum pellucidum is a common malformation (Ahmad et al., 2006; Garcia-Filion & Borchert, 2013a; Garcia-Filion et al., 2010). Schizencephaly, polymicrogyria and hydrocephalus are some other major neuroanatomical abnormalities identified with concomitant neurological deficits, seizures, behavioral abnormalities, and developmental delay. Pituitary abnormalities may include ectopic posterior pituitary, empty sella and absence of the pituitary infundibulum and lack of posterior pituitary bright spot (Phillips, Spear, & Brodsky, 2001). Those with severe brain malformations, hydrocephalus, seizures and/or neurological deficits should be monitored by a neurologist and/or neurosurgeon (Borchert, 2012).
http://dx.doi.org/10.1016/j.pedn.2017.03.011 0882-5963/© 2017 Elsevier Inc. All rights reserved.
Please cite this article as: Hozjan, I., Optic Nerve Hypoplasia: More Than Meets the Eye, Journal of Pediatric Nursing (2017), http://dx.doi.org/ 10.1016/j.pedn.2017.03.011
2
I. Hozjan / Journal of Pediatric Nursing xxx (2017) xxx–xxx
Septo-Optic Dysplasia Septo-optic dysplasia (SOD) is a clinical diagnosis, and has traditionally been made with the presence of two or more features of the classic triad of (1) optic nerve hypoplasia, either unilateral or bilateral, (2) midline brain defects including hypoplasia or absence of the septum pellucidum or corpus callosum, and (3) pituitary hormone deficiencies resulting in isolated to multiple hormone deficiencies (Kelberman & Dattani, 2008). However, the absence of a septum pellucidum or other midline malformations is not prognostic of hypothalamic–pituitary abnormalities, and ONH alone is an independent risk factor for hypothalamic–pituitary dysfunction in approximately 60–80 percent of cases (Ryabets-Lienhard et al., 2016). Neuroendocrine Effects Hypothalamic dysfunction and pituitary deficiencies are the most common source of nonvisual morbidity in ONH, and disruptions in hypothalamic homeostatic mechanisms impact pituitary gland function, temperature regulation, hunger behaviors (hyperphagia/hypophagia), thirst, and sleep–wake cycles (Garcia-Filion & Borchert, 2013a). There is correlation between severity of visual impairment and developmental delay to hypothalamic pituitary dysfunction (Rivkees, Fink, Nelson, & Borchert, 2010). Hyperprolactinemia is a marker for hypothalamic dysfunction (Vedin, Garcia-Filion, Fink, Borchert, & Geffner, 2012) and increases risk of other pituitary deficiencies. Overweight and obesity related to hypothalamic dysfunction and hyperphagia in ONH predisposes these children to lifelong morbidity (Ahmad et al., 2006). Hypopituitarism in ONH is a widely recognized clinical association and a lack of pituitary findings on imaging does not preclude the development of hypopituitarism in ONH (Ahmad et al., 2006). While pituitary deficiencies may occur at any age, the majority of children will experience one or more abnormality by age five years (Ahmad et al., 2006; Garcia-Filion et al., 2008; Oatman, McClellan, Olson, & Garcia-Filion, 2015; Vedin et al., 2012). Regular endocrine monitoring and follow-up is required. Growth hormone deficiency (GHD) is the most common deficiency in ONH and may present in infancy or evolve during childhood (Garcia-Filion et al., 2008; Haddad & Eugster, 2005; Oatman et al., 2015). Children with ONH require ongoing assessment of linear growth with evaluation of their growth hormone axis (IGF-1, IGFBP-3) with provocative growth hormone testing when levels are considered below reference range and/or linear growth slows. Central (secondary) hypothyroidism, the second most common pituitary deficiency in ONH (Ma, Fink, Geffner, & Borchert, 2010), may develop over time. Central congenital hypothyroidism may be missed on newborn screening (NBS) as initial thyroid stimulating hormone (TSH) testing is designed to test for congenital (primary) hypothyroidism with elevated TSH. Infants with ONH and central hypothyroidism have been shown to have lower TSH on NBS and were found to have significantly worse vision outcomes (Fink et al., 2012). Secondary adrenal insufficiency (AI) in ONH is a result of corticotropin-releasing hormone and/or adrenocorticotropic hormone (ACTH) deficiency. Infants and children should have repeated morning cortisol measurements and/or provocative ACTH stimulation testing for low random or morning cortisol levels. Those patients with a low or inadequate cortisol response will require daily oral glucocorticoids for maintenance and oral or injectable intramuscular glucocorticoid for stress dosing during illness or significant physical stress. Children with ONH are at risk of sudden death (Brodsky, Conte, Taylor, Hoyt, & Mrak, 1997; Donahue, Lavina, & Najjar, 2005) related to AI and diabetes insipidus. Diabetes insipidus (DI) as a result of deficiency of posterior pituitary gland derived anti-diuretic hormone tends to be less common (Djermane et al., 2016) though its presence may increase morbidity. DI may be challenging to evaluate in an infant or child. Classic findings
include polyuria, polydipsia, enuresis, dehydration, and symptoms of hypernatremia (restlessness, irritability, nausea, vomiting, lethargy, seizures and muscular twitching). Pubertal disturbances are common and may include absent, delayed, precocious and rapid tempo variations once started (Oatman et al., 2015). It is not uncommon to observe and manage precocious and/or rapid tempo pubertal development with gonadotropin-releasing hormone agonists in a young child who has isolated GHD and/or additional pituitary deficiencies. Evaluation of the hypothalamic–pituitary–gonadal axis (luteinizing hormone, follicle stimulating hormone, and estradiol in females or testosterone in males) may be completed early in the first 6 months of life during the transient phase of mini-puberty in infancy to identify possible hypothalamic hypogonadism concerns for the future. Otherwise, evaluation of precocious or delayed puberty is undertaken. Developmental Effects Developmental delay is a finding in a majority of patients with hypoplasia of the corpus callosum and hypothyroidism in either unilateral or bilateral ONH (Garcia-Filion et al., 2008) and may range from mild delays to significant and/or profound global delays. Autism spectrum disorder (ASD) is common in the visually impaired population, particularly among the profoundly visually impaired. ASD is highly prevalent in children with ONH (Garcia-Filion & Borchert, 2013a). Some behaviors and mannerisms that overlap in ASD and ONH include echolalia, pronoun reversals, stereotypic motor movements such as eye rubbing, hand movements (flapping, posturing), delays or limits in imaginative play, and atypical touching, smelling or exploration of new or foreign objects (Brown, Hobson, Lee, & Stevenson, 1997). As children with ONH develop and become more comfortable exploring and moving around their environments, their reciprocal social and communication behaviors improve and their repetitive behaviors and mannerisms may decrease. Diagnoses of ASD in very young children with vision impairment may not persist over time (Hobson & Lee, 2010; Williams, Fink, Zamora, & Borchert, 2014). Nursing and Team Considerations An individualized family-centered, multidisciplinary pediatric team approach is required to provide medically complex care and longterm surveillance. The pediatric nurse will provide the child and family with ongoing education, anticipatory guidance, and emotional support. The nurse will recommend and support appropriate strategies for optimal therapy adherence and pain management for necessary injections. The nurse will provide reinforcement of stress dosing needs for glucocorticoids in AI and management of sick days in AI and/or DI. Emergency care plans will be provided for primary caregivers, extended family, and the child's school. The nurse will reinforce the importance of wearable medical alert documentation. Additionally, the nurse will facilitate the coordination of care and multidisciplinary services for each child and family and identify when additional evaluations and early interventions may be appropriate. Developmental evaluations and early intervention are important to ensure that children with ONH are supported to maximize their functional outcomes. Children should be referred to early intervention programs, tailored for visually impaired children, for evaluation and treatment of possible developmental deficits and therapeutic ancillary services. These services may include: occupational therapy for oral motor skills, oral defensiveness or aversions, and a focus on feeding; physical therapy for large muscle and gross motor skill development such as ambulation, orientation and mobility; speech-language services for delays in communication development; a dietician to address failure to thrive and weight management issues; social work to provide emotional support and connection to resources; behavioral therapy for the child with emotional and/or behavioral issues related to attention
Please cite this article as: Hozjan, I., Optic Nerve Hypoplasia: More Than Meets the Eye, Journal of Pediatric Nursing (2017), http://dx.doi.org/ 10.1016/j.pedn.2017.03.011
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deficit disorder, ASD, or other neurological dysfunction; and a teacher for the visually impaired to optimize residual vision, orientation and mobilization and address harmful behaviors (e.g., eye pressing or poking). Children with ONH may qualify for special education under a number of categories including visual or cognitive impairment and/or multiple disabilities. Resources such as the MAGIC Foundation, support groups, and institutes or foundations for the blind will be beneficial for the child and family. In summary, the childhood challenges of ONH are complex and encompass a range of mild to profound neurodevelopmental and neurocognitive delays and disabilities, visual impairment, ASD, evolving hypopituitarism and obesity with concomitant risk for increased morbidity and mortality. Children with ONH require careful regular longterm multidisciplinary care, and follow up for medical management of ongoing growth and development, health surveillance, pituitary screening, developmental support, and anticipatory guidance. Acknowledgments Sincere thanks to Mark R. Palmert MD, PhD and Cheryl-Ann Ryans RN for their review and insight. References Ahmad, T., Garcia-Filion, P., Borchert, M., Kaufman, F., Burkett, L., & Geffner, M. (2006). Endocrinological and auxological abnormalities in young children with optic nerve hypoplasia: A prospective study. Journal of Pediatrics, 148, 78–84. http://dx.doi.org/ 10.1016/j.jpeds.2005.08.050. Atapattu, N., Ainsworth, J., Willshaw, H., Parulekar, M., MacPherson, L., Miller, C., ... Kirk, J. M. (2012). Septo-optic dysplasia: Antenatal risk factors and clinical features in a regional study. Hormone Research in Pædiatrics, 78, 81–87. http://dx.doi.org/10.1159/ 000341148. Borchert, M. (2012). Reappraisal of the optic nerve hypoplasia syndrome. Journal of Neuro-Ophthalmology, 32, 58–67. http://dx.doi.org/10.1097/WNO.0b013e31824442b8. Brodsky, M. C., Conte, F. A., Taylor, D., Hoyt, C. S., & Mrak, R. E. (1997). Sudden death in septo-optic dysplasia. Report of 5 cases. Archives of Ophthalmology, 115, 66–70. Brown, R., Hobson, R. P., Lee, A., & Stevenson, J. (1997). Are there "autistic-like" features in congenitally blind children? Journal of Child Psychology and Psychiatry and Allied Disciplines, 38, 693–703. Djermane, A., Elmaleh, M., Simon, D., Poidvin, A., Carel, J. C., & Leger, J. (2016). Central diabetes insipidus in infancy with or without hypothalamic adipsic hypernatremia syndrome: Early identification and outcome. Journal of Clinical Endocrinology and Metabolism, 101, 635–643. http://dx.doi.org/10.1210/jc.2015-3108. Donahue, S. P., Lavina, A., & Najjar, J. (2005). Infantile infection and diabetes insipidus in children with optic nerve hypoplasia. British Journal of Ophthalmology, 89, 1275–1277. http://dx.doi.org/10.1136/bjo.2005.069609. Fink, C., Vedin, A. M., Garcia-Filion, P., Ma, N. S., Geffner, M. E., & Borchert, M. (2012). Newborn thyroid-stimulating hormone in children with optic nerve hypoplasia: Associations with hypothyroidism and vision. Journal of AAPOS, 16, 418–423. http://dx.doi. org/10.1016/j.jaapos.2012.05.012.
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Please cite this article as: Hozjan, I., Optic Nerve Hypoplasia: More Than Meets the Eye, Journal of Pediatric Nursing (2017), http://dx.doi.org/ 10.1016/j.pedn.2017.03.011