Gillespie syndrome

Last updated
Gillespie syndrome
Other namesAniridia-cerebellar ataxia-intellectual disability, Partial aniridia-cerebellar ataxia-oligophrenia
Autosomal dominant - en.svg
Autosomal recessive - en.svg
Gillespie syndrome can be inherited in either an autosomal dominant (left) or autosomal recessive (right) pattern.

Gillespie syndrome, also called aniridia, cerebellar ataxia and mental deficiency, [1] [2] [3] is a rare genetic disorder. The disorder is characterized by partial aniridia (meaning that part of the iris is missing), ataxia (motor and coordination problems), and, in most cases, intellectual disability. It is heterogeneous, inherited in either an autosomal dominant or autosomal recessive manner. [4] Gillespie syndrome was first described by American ophthalmologist Fredrick Gillespie in 1965. [1] [3]

Contents

Presentation

The combination of muscular hypotonia and fixed dilated pupils in infancy is suspicious of Gillespie syndrome. [5] Early onset partial aniridia, cerebellar ataxia, and mental retardation are hallmark of syndrome. [6] The iris abnormality is specific and seems pathognomonic of Gillespie syndrome. [6] The aniridia consisting of a superior coloboma and inferior iris hypoplasia, foveomacular dysplasia. [7]

Atypical Gillespie syndrome associated with bilateral ptosis, exotropia, correctopia, iris hypoplasia, anterior capsular lens opacities, foveal hypoplasia, retinal vascular tortuosity, and retinal hypopigmentation. [8]

Neurological signs are nystagmus, mild craniofacial asymmetry, axial hypotonia, developmental delay, and mild mental retardation. [6] [7] Mariën P did not support the prevailing view of a global mental retardation as a cardinal feature of Gillespie syndrome but primarily reflect cerebellar induced neurobehavioral dysfunctions following disruption of the cerebrocerebellar anatomical circuitry that closely resembles the "cerebellar cognitive and affective syndrome" (CeCAS). [9]

Congenital pulmonary stenosis and helix dysplasia can be associated. [5]

Genetics

Gillespie syndrome is a heterogeneous disorder, and can be inherited in either an autosomal dominant or recessive manner. [4] [6] Autosomal dominant inheritance indicates that the defective gene responsible for a disorder is located on an autosome, and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.[ citation needed ]

Autosomal recessive inheritance means the defective gene responsible for the disorder is located on an autosome, but two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.[ citation needed ]

PAX6 gene analysis can also be helpful to distinguish between autosomal dominant aniridia and Gillespie syndrome. [5] However atypical Gillespie syndrome is associated mutation with PAX6 gene. [2] [8]

To elucidate the underlying genetic defects karyotyping and the search for de novo translocations especially of chromosome X and 11 should be performed. [5]

This condition is caused by mutations in the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) gene. [10] This gene is located on the short arm of chromosome 3 (3p26.1). Mutations in this gene have also been associated with spinocerebellar ataxia type 15 and 29.[ citation needed ]

Diagnosis

Brain MRI shows vermis atrophy or hypoplasic. [11] Cerebral and cerebellar atrophy with white matter changes in some cases. [6]

Treatment

History

  1. 1964 – GILLESPIE FD first described in two siblings with aniridia, cerebellar ataxia, and mental retardation. [1]
  2. 1971 – Sarsfield, J. K. described more cases in a family with normal NCV and muscle biopsy. [12]
  3. 1997 – Nelson J reported diffuse MRI abnormality in Cerebral and cerebellar atrophy with white matter changes suggested more diffuse disease. [6]
  4. 1998 – Dollfus H reported a patient with a phenotype suggestive of a chromosomal abnormality. [7]
  5. 2008 – Mariën P found limited cognitive deficit that closely resembles the "cerebellar cognitive and affective syndrome" (CeCAS). [9]

Related Research Articles

Cenani–Lenz syndactylism Medical condition

Cenani–Lenz syndactylism, also known as Cenani–Lenz syndrome or Cenani–syndactylism, is an autosomal recessive congenital malformation syndrome involving both upper and lower extremities.

Aniridia Absence of the iris, usually involving both eyes

Aniridia is the absence of the iris, a muscular structure that opens and closes the pupil to allow light into the eye. It is also responsible for eye color. Without it the central eye appears all black. It can be congenital, in which both eyes are usually involved, or caused by a penetrant injury. Isolated aniridia is a congenital disorder which is not limited to a defect in iris development, but is a panocular condition with macular and optic nerve hypoplasia, cataract, and corneal changes. Vision may be severely compromised and the disorder is frequently associated with a number of ocular complications: nystagmus, amblyopia, buphthalmos, and cataract. Aniridia in some individuals occurs as part of a syndrome, such as WAGR syndrome, or Gillespie syndrome.

Spinocerebellar ataxia Medical condition

Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of spinocerebellar ataxia at any given time. SCA is hereditary, progressive, degenerative, and often fatal. There is no known effective treatment or cure. SCA can affect anyone of any age. The disease is caused by either a recessive or dominant gene. In many cases people are not aware that they carry a relevant gene until they have children who begin to show signs of having the disorder.

Behr syndrome Medical condition

Behr syndrome is characterized by the association of early-onset optic atrophy with spinocerebellar degeneration resulting in ataxia, pyramidal signs, peripheral neuropathy and developmental delay.

Cerebellar ataxia is a form of ataxia originating in the cerebellum. Non-progressive congenital ataxia (NPCA) is a classical presentation of cerebral ataxias.

Arakawas syndrome II Medical condition

Arakawa's syndrome II is an autosomal dominant metabolic disorder that causes a deficiency of the enzyme tetrahydrofolate-methyltransferase; affected individuals cannot properly metabolize methylcobalamin, a type of Vitamin B12.

Papillorenal syndrome Medical condition

Papillorenal syndrome is an autosomal dominant genetic disorder marked by underdevelopment (hypoplasia) of the kidney and colobomas of the optic nerve.

Spinocerebellar ataxia type-13 Medical condition

Spinocerebellar ataxia type 13 (SCA13) is a rare autosomal dominant disorder, which, like other types of SCA, is characterized by dysarthria, nystagmus, and ataxia of gait, stance and the limbs due to cerebellar dysfunction. Patients with SCA13 also tend to present with epilepsy, an inability to run, and increased reflexes. This cerebellar dysfunction is permanent and progressive. SCA13 is caused by mutations in KCNC3, a gene encoding a voltage-gated potassium channel KV3.3. There are two known mutations in this gene causative for SCA13. Unlike many other types of SCA, these are not polyglutamine expansions but, rather, point mutations resulting in channels with no current or altered kinetics.

Vici syndrome, also called immunodeficiency with cleft lip/palate, cataract, hypopigmentation and absent corpus callosum, is a rare autosomal recessive congenital disorder characterized by albinism, agenesis of the corpus callosum, cataracts, cardiomyopathy, severe psychomotor retardation, seizures, immunodeficiency and recurrent severe infections. To date, about 50 cases have been reported.

Uner Tan Syndrome (UTS) is a syndrome that was discovered by the Turkish evolutionary biologist Üner Tan. People affected by UTS walk with a quadrupedal locomotion and often have severe learning disabilities. Tan postulated that this is an example of "reverse evolution" (atavism). The proposed syndrome was featured in the 2006 BBC2 documentary The Family That Walks On All Fours.

Norman–Roberts syndrome Medical condition

Norman–Roberts syndrome, is a rare form of microlissencephaly caused by a mutation in the RELN gene. A small number of cases have been described. The syndrome was first reported by Margaret Grace Norman and M. Roberts et al. in 1976.

VLDLR-associated cerebellar hypoplasia (VLDLRCH) is a rare autosomal recessive condition caused by a disruption of the VLDLR gene. First described as a form of cerebral palsy in the 1970s, it is associated with parental consanguinity and is found in secluded communities, with a number of cases described in Hutterite families.

OPHN1 Protein-coding gene in the species Homo sapiens

Oligophrenin-1 is a protein that in humans is encoded by the OPHN1 gene.

Acrofrontofacionasal dysostosis is an extremely rare disorder, characterized by intellectual disability, short stature, hypertelorism, broad notched nasal tip, cleft lip/palate, postaxial camptobrachypolysyndactyly, fibular hypoplasia, and anomalies of foot structure.

Pontocerebellar hypoplasia Medical condition

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare neurodegenerative disorders caused by genetic mutations and characterised by progressive atrophy of various parts of the brain such as the cerebellum or brainstem. Where known, these disorders are inherited in an autosomal recessive fashion. There is no known cure for PCH.

Autosomal recessive cerebellar ataxia type 1 Hereditary ataxia that has material basis in autosomal recessive inheritance

Autosomal recessive cerebellar ataxia type 1 (ARCA1) is a condition characterized by progressive problems with movement. Signs and symptoms of the disorder first appear in early to mid-adulthood. People with this condition initially experience impaired speech (dysarthria), problems with coordination and balance (ataxia), or both. They may also have difficulty with movements that involve judging distance or scale (dysmetria). Other features of ARCA1 include abnormal eye movements (nystagmus) and problems following the movements of objects with their eyes. The movement problems are slowly progressive, often resulting in the need for a cane, walker, or wheelchair.

Oculomotor apraxia (OMA), is the absence or defect of controlled, voluntary, and purposeful eye movement. It was first described in 1952 by the American ophthalmologist David Glendenning Cogan. People with this condition have difficulty moving their eyes horizontally and moving them quickly. The main difficulty is in saccade initiation, but there is also impaired cancellation of the vestibulo-ocular reflex. Patients have to turn their head in order to compensate for the lack of eye movement initiation in order to follow an object or see objects in their peripheral vision, but they often exceed their target. There is controversy regarding whether OMA should be considered an apraxia, since apraxia is the inability to perform a learned or skilled motor action to command, and saccade initiation is neither a learned nor a skilled action.

PMM2 deficiency Medical condition

PMM2 deficiency or PMM2-CDG is a very rare genetic disorder caused by mutations in PMM2. It is an autosomal recessive disorder. A defective copy of the PMM2 gene is the most common cause of a disease called “congenital disorders of glycosylation” or “PMM2-CDG”. PMM2-CDG is the most common of a growing family of more than 130 extremely rare inherited metabolic disorders. Only about 1000 children and adults have been reported worldwide.

COACH syndrome, also known as Joubert syndrome with hepatic defect, is a rare autosomal recessive genetic disease. The name is an acronym of the defining signs: cerebellar vermis aplasia, oligophrenia, congenital ataxia, coloboma and hepatic fibrosis. The condition is associated with moderate intellectual disability. It falls under the category of a Joubart Syndrome-related disorder (JSRD).

References

  1. 1 2 3 Gillespie, FD (Mar 1965). "Aniridia, cerebellar ataxia, and oligophrenia in siblings". Archives of Ophthalmology . 73 (3): 338–341. doi:10.1001/archopht.1965.00970030340008. PMID   14246186.
  2. 1 2 Online Mendelian Inheritance in Man (OMIM): 206700
  3. 1 2 synd/2006 at Who Named It?
  4. 1 2 Defreyn, A; Maugery, J; Chabrier, S; Coullet, J (Jan 2007). "Syndrome de Gillespie : un cas rare d'aniridie congénitale". Journal Français d'Ophthalmologie (in French). 30 (1): e1. doi:10.1016/s0181-5512(07)89554-4. PMID   17287663.
  5. 1 2 3 4 Kieslich, M; Vanselow, K; Wildhardt, G; Gebhardt, B; Weis, R; Böhles, H (Apr 2001). "[Present limitations of molecular biological diagnostics in Gillespie syndrome]". Klinische Pädiatrie . 213 (2): 47–49. doi:10.1055/s-2001-12875. PMID   11305191.
  6. 1 2 3 4 5 6 Nelson, J (Aug 1997). "Gillespie syndrome: a report of two further cases". American Journal of Medical Genetics . 71 (2): 134–8. doi:10.1002/(sici)1096-8628(19970808)71:2<134::aid-ajmg3>3.0.co;2-y. PMID   9217210.
  7. 1 2 3 Dollfus, H (Mar 1998). "Gillespie syndrome phenotype with a t(X;11)(p22.32;p12) de novo translocation". American Journal of Ophthalmology . 125 (3): 397–9. doi:10.1016/s0002-9394(99)80157-3. PMID   9512164.
  8. 1 2 Ticho, BH; Hilchie-Schmidt, C; Egel, RT; Traboulsi, EI; Howarth, RJ; Robinson, D (Dec 2006). "Ocular findings in Gillespie-like syndrome: association with a new PAX6 mutation". Ophthalmic Genetics . 27 (4): 145–149. doi:10.1080/13816810600976897. PMID   17148041. S2CID   21415333.
  9. 1 2 Mariën, P; Brouns, R; Engelborghs, S; Wackenier, P; Verhoeven, J; Ceulemans, B; De Deyn, PP (Jan 2008). "Cerebellar cognitive affective syndrome without global mental retardation in two relatives with Gillespie syndrome". Cortex . 44 (1): 54–67. doi:10.1016/j.cortex.2005.12.001. PMID   18387531. S2CID   16768408.
  10. ↑ Paganini L, Pesenti C, Milani D, Fontana L, Motta S, Sirchia SM, Scuvera G, Marchisio P, Esposito S, Cinnante CM, Tabano SM, Miozzo MR (2018) A novel splice site variant in ITPR1 gene underlying recessive Gillespie syndrome. Am J Med Genet A doi: 10.1002/ajmg.a.38704
  11. ↑ Boughamoura, L; Yacoub, M; Abroug, M; Chabchoub, I; Bouguezzi, R; Charfeddine, L; Amri, F; Essoussi, A-S (Oct 2006). "[Gillespie syndrome: 2 familial cases]". Archives de Pédiatrie . 13 (10): 1323–1325. doi:10.1016/j.arcped.2006.06.028. PMID   16919425.
  12. ↑ Sarsfield, JK (Aug 1971). "The syndrome of congenital cerebellar ataxia, aniridia and mental retardation". Developmental Medicine & Child Neurology . 13 (4): 508–11. doi:10.1111/j.1469-8749.1971.tb03057.x. PMID   5558750. S2CID   28822017.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.