Handbook of Genetic Counseling/Septo-optic dysplasia

Septo-optic dysplasia

Introduction and Contracting

• What is your understanding about why you were referred to genetics?
• What are your main concerns for _______?
• Do you have any questions for us today?
• Outline the session:
  • Want to first take a family medical history
  • Then make sure the medical information I have is correct
  • We will discuss the information we obtain with Dr. Doktour
  • Then we will answer all your questions and explain what we believe might be the cause of the problems ____ has experienced

Pedigree

• Learning difficulties or mental retardation
• Birth defects
• Seizures
• Eye problems
• Problems with growth
• Infertility
• History of pregnancy losses
• Anyone died at a young age or unexpectedly
• Chronic health problem
• Anything that seems to be running in your family

Take medical history

(follow form)

• Explain how mosaic turner syndrome was ruled out as an explanation for her short stature and absent periods

Introduce septo-optic dysplasia also called SOD

• A rare disorder where some of the structures in the middle of the brain don't form properly
• This can lead to changes in the way they function and a number of symptoms and characteristic findings
• A number of findings on ______'s MRI suggested that she might have septo-optic dysplasia
• Septo refers to the center structure of the brain
• The septum pellucidum is a membrane that separates one of the fluid filled spaces in the brain (show picture)
• This membrane is missing in ________.
• The pituitary gland is also located in the center of the brain and does not seem to be functioning properly in _____.
• The term optic refers to the optic nerve, which is what carries the messages from the eyes to the brain
• ______'s optic nerves are underdeveloped and small
• Dysplasia means that these structures are not formed properly

Symptoms of SOD

• The problems that can occur in individuals with SOD vary and can range from mild or serious
• A person with SOD can have a combination of any number of symptoms or characteristics
  • Eye problems
    • If the optic nerve is small or not developed properly will have fewer connections to the brain and can therefore have poor vision
    • This is called optic nerve hypoplasia (ONH)
    • Vision doesn't usually decrease over time though
    • Most with ONH also have unusual eye movements where the eyes move around and don't focus well (nystagmus)
  • Brain Structure and Function
    • Septum pellucidum missing (agenesis)
    • Some have an abnormal corpus callosum which is the group of nerve fibers connecting the brain
    • Other structural changes (larger than usual fluid filled cavities (ventricles), and fluid filled sacs in the ventricles (cysts) )
    • Sometimes changes in structure alter function and sometimes there is no brain function affected
    • Can be mildly to severely affected and cause developmental delays and cognitive problems
    • Some also have seizures
• Pituitary Gland
  • • Found in middle of brain and is master control gland
    • Makes important chemicals (hormones) which direct other glands in other parts of body to make other hormones
    • These other hormones are needed for things such as proper growth of body, energy control, sexual development

GH (growth hormone)

• About 6:10 children with ONH don't make enough growth hormone
• Can be treated with growth hormone shots
• GH also necessary after growth is complete to maintain bone strength and normal metabolism

Thyroid hormone can be lacking in kids with ONH/SOD

• Pituitary releases signal TSH to tell thyroid gland in neck to make thyroxin
• Thyroxin necessary for growth and metabolism
• Without enough can cause: poor growth, weight gain, slowing of mental function, feeling cold, irregular periods, dry skin, brittle nails, hair loss
• Can be replaced with pills taken every day

Gonadotropins (FSH and LH)

• Signal the ovaries and testes to produce sex hormones
• Without sex hormones sexual development may be delayed

Cortisol

• Made by adrenal glands above the kidneys
• ACTH from pituitary tells adrenal gland to make cortisol
• Increased amounts of cortisol needed when injured or sick
• If pituitary doesn't work right in telling adrenal glands to make more than may need to take cortisol pills daily

ADH (anti-diuretic hormone)

• Keeps water in the body by controlling amount of urine
• Without enough may lose too much water
• Feel thirsty, dry mouth, but urinates a lot
• May become dehydrated and have problems (called diabetes insipidus or water diabetes)
• Treatment available

Prolactin

• May have high prolactin
• Leads to no known health problems
• Used to test how pituitary is functioning

Services

• Children may need many tests and services
• Often followed by Ophthalmology, Endocrinology and Neurology
• Need early intervention
• May need IEP in school
• Services may include PT, OT, speech therapy depending on child's needs
• Special needs for those with severe vision problems

Etiology of SOD

• Exact cause of SOD is not known
• Probably due to a combination of genetic and environmental influences early in gestation at about 6 wks gestation
• Usually thought to be sporadic meaning that it is not something that was inherited
• Cases have been reported where it appears to be autosomal recessive (presence of two copies of altered copies of a gene)
• Mutations were in homeodomain of HESX1 gene
• Found similar phenotype in mice that were mutant for homologous gene Hesx1
• Also identified heterozygous mutations in HESX1 that correlated with milder pituitary phenotypes

Recurrence Risks

• Dependent on whether it is a sporadic case or a mutation is present
• Few documented reports of affected siblings
• Testing was available on a research basis for the HESX1 gene as of first part of Nov. 2001, but we would need to contact the researcher to see if they are still searching for mutations (researcher is in UK).

Psychosocial considerations

• May be a lot of new information and it is not simple
• We have some written information that you can read through if you would like
• May regret not having diagnosis earlier
• May feel that more could have been done if it was diagnosed earlier
• What are plans for her in the future
• Will she live at home or in a group home
• Is she connected with anyone who can help her with a job placement when school is done

Patient resources/references

• Focus Families - parent support

www.focusfamilies.org

• The Magic Foundation for Children's Growth

www.magicfoundation.org/sodp.html

• Hormone Abnormalities in SOD: A Reference Guide

Mary J. Sarrantonio, MD, pediatric endocrinologist

• Optic Nerve Hypoplasia: A Guide for Parents

Francine Ratner Kaufman, MD

Neal Kaufman, MD

Mark Borchert, MD

• National Institute of Neurological Disorders and Stroke

www.ninds.nih.bov/health_and_medical/disorders/septo-optic.html

References in primary literature

• Hellstrom A, et al. Children with septo-optic dysplasia - how to improve and sharpen the diagnosis. Hormone Research vol. 53 Suppl 1: 19-25 (2000).
• Ouvrier R and Billson F. Optic nerve hypoplasia: a review. Journal of Child Neurology. Vol 1, no. 3 : 181-188. (1986).
• Dattani M L, et al. Molecular genetics of septo-optic dysplasia. Hormone Research. Vol 53 Suppl 1: 26-33. (2000).

Notes

The information in this outline was last updated in 2002.