Gillespie syndrome

Gillespie syndrome
Classification and external resources
ICD-10	G11.05
ICD-9-CM	759.89
OMIM	206700
DiseasesDB	32735

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]

History

1964 - GILLESPIE FD first described in two siblings with aniridia, cerebellar ataxia, and mental retardation.^[1]
1971 - Sarsfield, J. K. described more cases in a family with normal NCV and muscle biopsy.^[5]
1997 - Nelson J reported diffuse MRI abnormality in Cerebral and cerebellar atrophy with white matter changes suggested more diffuse disease.^[6]
1998 - Dollfus H reported a patient with a phenotype suggestive of a chromosomal abnormality.^[7]
2008 - Mariën P found limited cognitive deficit that closely resembles the "cerebellar cognitive and affective syndrome" (CeCAS).^[8]

Clinical Features

The combination of muscular hypotonia and fixed dilated pupils in infancy is suspicious of Gillespie syndrome.^[9] 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.^[10]

Neurological signs ar 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).^[8]

Congenital pulmonary stenosis and helix dysplasia can be associated.^[9]

Imaging

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

Genetics

Gillespie syndrome can be inherited in either an autosomal dominant (left) or autosomal recessive (right) pattern.

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.

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.

PAX6 gene analysis can also be helpful to distinguish between autosomal dominant aniridia and Gillespie syndrome.^[9] However Atypical Gillespie syndrome is associated mutation with PAX6 gene.^[2]^[10]

To illucidate the underlying genetic defects karyotyping and the search for de novo translocations especially of chromosome X and 11 should be performed.^[9]

References

1 2 3 Gillespie, FD (Mar 1965). "Aniridia, cerebellar ataxia, and oligophrenia in siblings". Archives of Ophthalmology. 73: 338–341. doi:10.1001/archopht.1965.00970030340008. PMID 14246186.
1 2 Online Mendelian Inheritance in Man (OMIM) 206700
1 2 synd/2006 at Who Named It?
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. PMID 17287663.
↑ Sarsfield, JK (Aug 1971). "The syndrome of congenital cerebellar ataxia, aniridia and mental retardation". Developmental Medicine & Child Neurology. 13 (4): 508–11. PMID 5558750.
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.
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.
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.
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.
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.
↑ 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.

External links

Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies

(1) Basic domains

1.2	Feingold syndrome Saethre–Chotzen syndrome

1.3	Tietz syndrome

(2) Zinc finger
DNA-binding domains

2.1	(Intracellular receptor): Thyroid hormone resistance Androgen insensitivity syndrome PAIS MAIS CAIS Kennedy's disease PHA1AD pseudohypoaldosteronism Estrogen insensitivity syndrome X-linked adrenal hypoplasia congenita MODY 1 Familial partial lipodystrophy 3 SF1 XY gonadal dysgenesis

2.2	Barakat syndrome Tricho–rhino–phalangeal syndrome

2.3	Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome Denys–Drash syndrome Duane-radial ray syndrome MODY 7 MRX 89 Townes–Brocks syndrome Acrocallosal syndrome Myotonic dystrophy 2

2.5	Autoimmune polyendocrine syndrome type 1

(3) Helix-turn-helix domains

3.1	ARX Ohtahara syndrome Lissencephaly X2 MNX1 Currarino syndrome HOXD13 SPD1 Synpolydactyly PDX1 MODY 4 LMX1B Nail–patella syndrome MSX1 Tooth and nail syndrome OFC5 PITX2 Axenfeld syndrome 1 POU4F3 DFNA15 POU3F4 DFNX2 ZEB1 Posterior polymorphous corneal dystrophy Fuchs' dystrophy 3 ZEB2 Mowat–Wilson syndrome

3.2	PAX2 Papillorenal syndrome PAX3 Waardenburg syndrome 1&3 PAX4 MODY 9 PAX6 Gillespie syndrome Coloboma of optic nerve PAX8 Congenital hypothyroidism 2 PAX9 STHAG3

3.3	FOXC1 Axenfeld syndrome 3 Iridogoniodysgenesis, dominant type FOXC2 Lymphedema–distichiasis syndrome FOXE1 Bamforth–Lazarus syndrome FOXE3 Anterior segment mesenchymal dysgenesis FOXF1 ACD/MPV FOXI1 Enlarged vestibular aqueduct FOXL2 Premature ovarian failure 3 FOXP3 IPEX

3.5	IRF6 Van der Woude syndrome Popliteal pterygium syndrome

(4) β-Scaffold factors
with minor groove contacts

4.2	Hyperimmunoglobulin E syndrome

4.3	Holt–Oram syndrome Li–Fraumeni syndrome Ulnar–mammary syndrome

4.7	Campomelic dysplasia MODY 3 MODY 5 SF1 SRY XY gonadal dysgenesis Premature ovarian failure 7 SOX10 Waardenburg syndrome 4c Yemenite deaf-blind hypopigmentation syndrome

4.11	Cleidocranial dysostosis

(0) Other transcription factors

0.6	Kabuki syndrome

Ungrouped

Transcription coregulators

Coactivator:	CREBBP Rubinstein–Taybi syndrome

Corepressor:	HR (Atrichia with papular lesions)

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