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Disease Profile

Gillespie syndrome

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.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

G11.0

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)

Aniridia, cerebellar ataxia and mental deficiency

Categories

Congenital and Genetic Diseases; Eye diseases; Nervous System Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 1065

Definition
A rare, congenital, neurological disorder characterized by the association of partial bilateral aniridia with non-progressive cerebellar ataxia, and intellectual disability.

Epidemiology
To date, less than 30 patients have been reported in the literature.

Clinical description
Aniridia is visible at birth as fixed dilated pupils and is associated with photobia. It can be accompanied with additional ocular findings such as foveal, patchy iris and/or optic nerve hypoplasia, retinal hypopigmentation, and/or pigmentary macular changes leading to reduced visual acuity. Cataract and corneal opacities are never observed. Non-progressive cerebellar ataxia is associated with delayed developmental milestones and hypotonia (visible from the first year of life), gait and balance disorders with incoordination, intention tremor, and scanning speech. Intellectual disability is variable. Mild facial dysmorphic features may be observed such as high forehead, hypertelorism, epicanthic folds, depressed nasal bridge with anteverted nostrils, and thin upper lip. The cases referred to as atypical Gillespie syndrome correspond to those showing a more complex phenotype, associating additional ocular findings and a mild dysmorphic face.

Etiology
The etiology is unknown. Some atypical cases have been linked to mutations in the PAX6 gene (11p13), encoding a transcriptional regulator expressed in ocular, cerebral, olfactory, and pancreatic tissues. One case has also been reported to be due to a de novo translocation of chromosome X and 11 t(X;11) (p22.32;p12), but with no involvement of the PAX6 gene.

Diagnostic methods
A presumptive diagnosis can be made in the first months of life: on slit lamp examination, the pupil border of the iris typically shows a scalloped, 'festooned' edge with iris strands extending onto the anterior lens surface at regular intervals. In many cases, neuroimaging studies (CT scan, MRI) show cerebellar hypoplasia or atrophy, especially of the vermis, with occasional white matter changes, and diffuse atrophy of the cerebral hemispheres, brainstem and frontal cortex.

Differential diagnosis
Differential diagnosis includes Marinesco-Sjögren syndrome (see this term) in which congenital cataract is present, as well as cerebellar ataxia, intellectual disability, and aniridia (see this term).

Genetic counseling
Sporadic and familial cases have been observed. Although some reported families are compatible with autosomal dominant inheritance, Gillespie syndrome is more likely to be an autosomal recessive condition.

Management and treatment
Management includes regular ophthalmologic evaluation with prescription of optical aids, physical, speech and occupational therapy for muscular re-education.

Prognosis
There are no reports on the natural history of the disease. Prognosis depends on the proper management and anticipation of ocular and mental symptoms and disabilities.

Visit the Orphanet disease page for more resources.

Symptoms

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
Aniridia
Absent iris
0000526
Ataxia
0001251
Global developmental delay
0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Mask-like facies
Expressionless face
Lack of facial expression
Mask-like facial appearance

[ more ]

0000298
30%-79% of people have these symptoms
Abnormality of movement
Movement disorder
Unusual movement

[ more ]

0100022
Muscular hypotonia
Low or weak muscle tone
0001252
Scanning speech
Explosive speech
0002168
5%-29% of people have these symptoms
Abnormality of the pulmonary artery
Abnormality of lung artery
0004414
Hearing abnormality
Abnormal hearing
0000364
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Autosomal recessive inheritance
0000007
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum

[ more ]

0001321
Hypoplasia of the iris
Underdeveloped iris
0007676
Motor delay
0001270
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Postural tremor
0002174
Slurred speech
0001350
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505

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

    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 Gillespie syndrome. Click on the link to view a sample search on this topic.