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Disease Profile

Septo-optic dysplasia spectrum

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

Q04.4

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Septooptic dysplasia; De morsier syndrome; Septo-optic dysplasia with growth hormone deficiency;

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Eye diseases;

Summary

Septo-optic dysplasia is a disorder of early brain and eye development. The most common features are underdevelopment (hypoplasia) of the eye (optic) nerve, abnormal formation of structures along the midline of the brain such as the absence of the septum pellucidum and the corpus callosum, and a small pituitary (pituitary hypoplasia). Signs and symptoms may include blindness in one or both eyes, an abnormal pupil dilation in response to light, nystagmus (abnormal movement of the eyes), low muscular tone and hormonal problems. Additional features may include recurring seizures, delayed development, intellectual disability, jaundice (yellow-ish skin), precocious puberty, short stature, sleep problems, obesity, lack of smell (anosmia), hearing loss and heart anomalies.[1][2][3]

Although the cause is unknown in most cases, very few people with SOD may have variations (mutations) in the HESX1 OTX2, SOX2 or SOX3 genes.[1][4] Other factors that may be involved are viral infections, certain medications and a blood flow disruption.[1][4][5] Typically, people do not have a family history of septo-optic dysplasia. However, there have been a few cases in which multiple family members have been diagnosed. In these cases inheritance can be autosomal recessive or autosomal dominant.[1][3] Although there is no cure for this condition, the treatment is directed toward the specific symptoms in each individual. Children with possible SOD must be kept under careful hormonal follow-up, and, if present, hormone deficiencies should be treated with hormone replacement therapy.[3][4]

Symptoms

Typically, the symptoms develop in 3 organs, the brain (which have abnormal formation of midline structures), the eyes (due to optic nerve hypoplasia), and pituitary (due to hypoplasia. About one third of the patients present with all of the three main features. However, some symptoms may not appear until childhood or later. Symptoms may include:[1][3][6]

  • Blindness in one or both eyes
  • Pupil dilation in response to light
  • Nystagmus (a rapid, involuntary to-and-fro movement of the eyes)
  • Inward and outward deviation of the eyes
  • Hypotonia (low muscle tone)
  • Seizures

Other common features are: [1][3][2][4][5]

  • Short stature due to lack of growth hormone deficiency (the most common hormonal abnormality)
  • Abnormal thirst, hunger, and body temperature due to underdevelopment of the hypothalamus, a region of the brain responsible for regulating basic body functions.
  • Low blood sugar
  • Genital abnormalities
  • Problems with sexual development or precocious puberty
  • Sleep difficulties
  • Obesity
  • Jaundice
  • Intellectual disability or learning disabilities
  • Developmental delay related to vision impairment or neurological problems
  • Anosmia
  • Heart problems

Pituitary hormone insufficiencies may evolve over time necessitating life-long medical follow-up.[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Septo-optic dysplasia
0100842
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505
30%-79% of people have these symptoms
Agenesis of corpus callosum
0001274
Anterior pituitary hypoplasia
Underdeveloped pituitary gland
0010627
Cleft palate
Cleft roof of mouth
0000175
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Hemiplegia/hemiparesis
Paralysis or weakness of one side of body
0004374
Hypoplasia of penis
Underdeveloped penis
0008736
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Seizure
0001250
Short stature
Decreased body height
Small stature

[ more ]

0004322
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
5%-29% of people have these symptoms
Abnormality of cardiovascular system morphology
0030680
Anosmia
Lost smell
0000458
Aplasia/Hypoplasia of the cerebellum
Absent/small cerebellum
Absent/underdeveloped cerebellum

[ more ]

0007360
Autism
0000717
Constipation
0002019
Diabetes insipidus
0000873
Dry skin
0000958
Esophageal atresia
Birth defect in which part of esophagus did not develop
0002032
Fatigue
Tired
Tiredness

[ more ]

0012378
Global developmental delay
0001263
Hypohidrosis
Decreased ability to sweat
Decreased sweating
Sweating, decreased

[ more ]

0000966
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Maternal diabetes
gestational diabetes
0009800
Obesity
Having too much body fat
0001513
Polydipsia
Extreme thirst
0001959
Sensorineural hearing impairment
0000407
Sleep disturbance
Difficulty sleeping
Trouble sleeping

[ more ]

0002360
Tracheoesophageal fistula
0002575
Percent of people who have these symptoms is not available through HPO
Absent septum pellucidum
0001331
Autosomal dominant inheritance
0000006
Autosomal recessive inheritance
0000007
Growth hormone deficiency
0000824
Optic disc hypoplasia
0007766
Optic nerve hypoplasia
0000609
Polydactyly
More than five fingers or toes on hands or feet
0010442
Psychomotor retardation
0025356
Short finger
Stubby finger
0009381

Cause

In most cases of septo-optic dysplasia, the cause of the disorder is unknown. Researchers suspect that a combination of genetic and environmental factors may play a role in causing this disorder. Proposed environmental risk factors include viral infections, specific medications, and a disruption in blood flow to certain areas of the brain during critical periods of development.[1]

At least three genes have been associated with septo-optic dysplasia, although mutations in these genes appear to be rare causes of this disorder. The three genes, HESX1, OTX2, and SOX2, all play important roles in early development. In particular, they are essential for the formation of the eyes, the pituitary gland, and structures at the front of the brain (the forebrain) such as the optic nerves. Mutations in any of these genes disrupt the early development of these structures, which leads to the major features of septo-optic dysplasia.[1]

Researchers are looking for additional genetic changes that contribute to septo-optic dysplasia.[1]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment is directed toward the specific symptoms in each individual and may require a team of specialists including pediatricians, ophthalmologists, neurologists, and endocrinologists. If present, hormone deficiencies may be treated with hormone replacement therapy. Vision problems are generally not treatable. Special services that may be useful include vision, physical, and occupational therapies.[3][6]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Social Networking Websites

        Organizations Providing General Support

          Learn more

          These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

          Where to Start

            In-Depth Information

            • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Septo-optic dysplasia spectrum. Click on the link to view a sample search on this topic.

              References

              1. Septo-optic dysplasia. Genetics Home Reference. March 2010; https://ghr.nlm.nih.gov/condition/septo-optic-dysplasia.
              2. Webb EA & Dattani MT. Septo-optic dysplasia. European Journal of Human Genetics. 2010; 18(4):393-397. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987262/.
              3. Borchert MS. Optic Nerve Hypoplasia. NORD. 2015; https://rarediseases.org/rare-diseases/optic-nerve-hypoplasia/.
              4. Saranac L & Gucev Z. New insights into septo-optic dysplasia. Pril (Makedon Akad Nauk Umet Odd Med Nauki). 2014; 35(1):123-7. https://www.ncbi.nlm.nih.gov/pubmed/24802313.
              5. Garne E, Rissmann A, Addor MC et al. Epidemiology of septo-optic dysplasia with focus on prevalence and maternal age A EUROCAT study.. Eur J Med Genet. May 10, 2018; 1769-7212(18):30149-6. https://www.ncbi.nlm.nih.gov/pubmed/29753093.
              6. NINDS Septo-Optic Dysplasia Information Page. National Institute of Neurological Disorders and Stroke (NINDS). https://www.ninds.nih.gov/Disorders/All-Disorders/Septo-Optic-Dysplasia-Information-Page. Accessed 1/25/2017.
              7. Dattani M, Webb E. Septo-optic dysplasia spectrum. Orphanet. February 2010; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=3157.

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