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Gillespie syndrome(GLSP)

MedGen UID:
96563
Concept ID:
C0431401
Disease or Syndrome
Synonyms: Aniridia, cerebellar ataxia, and mental deficiency; Aniridia-cerebellar ataxia-intellectual disability syndrome; GLSP
SNOMED CT: Gillespie syndrome (253176002); Aniridia, cerebellar ataxia, intellectual disability syndrome (253176002)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): ITPR1 (3p26.1)
 
Monarch Initiative: MONDO:0008795
OMIM®: 206700
Orphanet: ORPHA1065

Definition

Gillespie syndrome (GLSP) is usually diagnosed in the first year of life by the presence of fixed dilated pupils in a hypotonic infant. Affected individuals have a characteristic form of iris hypoplasia in which the pupillary border of the iris exhibits a scalloped or 'festooned' edge, with iris strands extending onto the anterior lens surface at regular intervals. The key extraocular features of Gillespie syndrome are congenital hypotonia, progressive cerebellar hypoplasia, and ataxia, as well as variable cognitive impairment that is usually mild (summary by Gerber et al., 2016 and McEntagart et al., 2016). [from OMIM]

Additional description

From MedlinePlus Genetics
Gillespie syndrome is a disorder that involves eye abnormalities, weak muscle tone from birth (congenital hypotonia), problems with balance and coordinating movements (ataxia), and mild to moderate intellectual disability.

Gillespie syndrome is characterized by underdevelopment (hypoplasia) of the colored part of the eye (the iris). In most affected individuals, part of the iris is missing (partial aniridia) in both eyes. In addition, the irises have a characteristic uneven pattern known as "scalloping" at the inner (pupillary) edge. The pupils are enlarged (dilated) and are fixed, which means they do not get smaller (constrict) in response to light. These abnormalities are thought to result from problems in the development or maintenance of the tiny muscles that allow the pupil to contract (sphincter pupillae). The eye abnormalities can cause blurry vision (reduced visual acuity) and increased sensitivity to light (photophobia). Rapid, involuntary eye movements (nystagmus) can also occur in Gillespie syndrome.

The balance and movement problems in Gillespie syndrome result from hypoplasia of the cerebellum, which is the part of the brain that coordinates movement. This abnormality can cause hypotonia and delayed development of motor skills such as walking. In addition, difficulty controlling the muscles of the mouth can lead to delayed speech development. The difficulties with coordination generally become noticeable in early childhood when the individual is learning these skills. People with Gillespie syndrome usually continue to have an unsteady pattern of walking (gait) and speech problems throughout life.

Other features of Gillespie syndrome can include abnormalities in the bones of the spine (vertebrae) and malformations of the heart.  https://medlineplus.gov/genetics/condition/gillespie-syndrome

Clinical features

From HPO
Imperforate hymen
MedGen UID:
57775
Concept ID:
C0152436
Congenital Abnormality
A congenital disorder where the hymen (a membrane that surrounds or partially covers the external vaginal opening) does not have an opening and completely obstructs the vagina.
Short fourth metatarsal
MedGen UID:
336358
Concept ID:
C1848514
Finding
Short fourth metatarsal bone.
Areflexia of lower limbs
MedGen UID:
347285
Concept ID:
C1856694
Finding
Inability to elicit tendon reflexes in the lower limbs.
Pulmonic stenosis
MedGen UID:
408291
Concept ID:
C1956257
Disease or Syndrome
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis).
Truncus arteriosus
MedGen UID:
892804
Concept ID:
C4020867
Congenital Abnormality
A single arterial trunk arises from the cardiac mass. The pulmonary arteries, aorta and coronary arteries arise from this single trunk with no evidence of another outflow tract.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Cholelithiasis
MedGen UID:
3039
Concept ID:
C0008350
Disease or Syndrome
Hard, pebble-like deposits that form within the gallbladder.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Cerebral palsy
MedGen UID:
854
Concept ID:
C0007789
Disease or Syndrome
Cerebral palsy describes a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication, and behavior, by epilepsy, and by secondary musculoskeletal problems.
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Intellectual disability, moderate
MedGen UID:
7680
Concept ID:
C0026351
Mental or Behavioral Dysfunction
Moderate mental retardation is defined as an intelligence quotient (IQ) in the range of 35-49.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Abnormal pyramidal sign
MedGen UID:
68582
Concept ID:
C0234132
Sign or Symptom
Functional neurological abnormalities related to dysfunction of the pyramidal tract.
Abnormality of extrapyramidal motor function
MedGen UID:
115941
Concept ID:
C0234133
Sign or Symptom
A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless).
Postural tremor
MedGen UID:
66696
Concept ID:
C0234378
Sign or Symptom
A type of tremors that is triggered by holding a limb in a fixed position.
Slurred speech
MedGen UID:
65885
Concept ID:
C0234518
Finding
Abnormal coordination of muscles involved in speech.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Cerebellar vermis atrophy
MedGen UID:
149271
Concept ID:
C0742028
Disease or Syndrome
Wasting (atrophy) of the vermis of cerebellum.
Delayed gross motor development
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Diffuse cerebellar atrophy
MedGen UID:
343184
Concept ID:
C1854699
Finding
Diffuse unlocalised atrophy affecting the cerebellum.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Oculomotor apraxia
MedGen UID:
483686
Concept ID:
C3489733
Disease or Syndrome
Ocular motor apraxia is a deficiency in voluntary, horizontal, lateral, fast eye movements (saccades) with retention of slow pursuit movements. The inability to follow objects visually is often compensated by head movements. There may be decreased smooth pursuit, and cancelation of the vestibulo-ocular reflex.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Abnormal flash visual evoked potentials
MedGen UID:
870329
Concept ID:
C4024772
Finding
Anomaly of the visual evoked potentials elicited by a flash stimulus, generally a flash of light subtending an angle of at least 20 degrees of the visual field and presented in a dimly lit room.
Specific learning disability
MedGen UID:
871302
Concept ID:
C4025790
Mental or Behavioral Dysfunction
Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence.
Delayed ability to stand
MedGen UID:
1370611
Concept ID:
C4476709
Finding
A failure to achieve the ability to stand up at an appropriate developmental stage. Most children begin to walk alone at 11 to 15 months of age. On average, children can stand while holding on at the age of 9 to 10 months, can pull up to stand and walk with one hand being held at 12 months, and can stand alone and walk well at 18 months.
Delayed ability to sit
MedGen UID:
1368737
Concept ID:
C4476710
Finding
A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age.
Thin corpus callosum
MedGen UID:
1785336
Concept ID:
C5441562
Anatomical Abnormality
An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration).
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Poor head control
MedGen UID:
322809
Concept ID:
C1836038
Finding
Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Aplasia of the pectoralis major muscle
MedGen UID:
869784
Concept ID:
C4024213
Anatomical Abnormality
Absence of the pectoralis major muscle.
Abnormal facial shape
MedGen UID:
98409
Concept ID:
C0424503
Finding
An abnormal morphology (form) of the face or its components.
Precocious puberty
MedGen UID:
18752
Concept ID:
C0034013
Disease or Syndrome
The onset of secondary sexual characteristics before a normal age. Although it is difficult to define normal age ranges because of the marked variation with which puberty begins in normal children, precocious puberty can be defined as the onset of puberty before the age of 8 years in girls or 9 years in boys.
Congenital aniridia
MedGen UID:
1941
Concept ID:
C0003076
Congenital Abnormality
PAX6-related aniridia occurs either as an isolated ocular abnormality or as part of the Wilms tumor-aniridia-genital anomalies-retardation (WAGR) syndrome. Aniridia is a pan ocular disorder affecting the cornea, iris, intraocular pressure (resulting in glaucoma), lens (cataract and lens subluxation), fovea (foveal hypoplasia), and optic nerve (optic nerve coloboma and hypoplasia). Individuals with aniridia characteristically show nystagmus and impaired visual acuity (usually 20/100 - 20/200); however, milder forms of aniridia with subtle iris architecture changes, good vision, and normal foveal structure do occur. Other ocular involvement may include strabismus and occasionally microphthalmia. Although the severity of aniridia can vary between and within families, little variability is usually observed in the two eyes of an affected individual. WAGR syndrome. The risk for Wilms tumor is 42.5%-77%; of those who develop Wilms tumor, 90% do so by age four years and 98% by age seven years. Genital anomalies in males can include cryptorchidism and hypospadias (sometimes resulting in ambiguous genitalia), urethral strictures, ureteric abnormalities, and gonadoblastoma. While females typically have normal external genitalia, they may have uterine abnormalities and streak ovaries. Intellectual disability (defined as IQ <74) is observed in 70%; behavioral abnormalities include attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, anxiety, depression, and obsessive-compulsive disorder. Other individuals with WAGR syndrome can have normal intellect without behavioral problems.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Hypoplasia of the iris
MedGen UID:
91029
Concept ID:
C0344539
Congenital Abnormality
Congenital underdevelopment of the iris.
Foveal hypoplasia
MedGen UID:
393047
Concept ID:
C2673946
Finding
Underdevelopment of the fovea centralis.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGillespie syndrome
Follow this link to review classifications for Gillespie syndrome in Orphanet.

Recent clinical studies

Etiology

Frisk S, Wachtmeister A, Laurell T, Lindstrand A, Jäntti N, Malmgren H, Lagerstedt-Robinson K, Tesi B, Taylan F, Nordgren A
Mol Genet Genomic Med 2022 Apr;10(4):e1880. Epub 2022 Feb 4 doi: 10.1002/mgg3.1880. PMID: 35118825Free PMC Article
De Silva D, Williamson KA, Dayasiri KC, Suraweera N, Quinters V, Abeysekara H, Wanigasinghe J, De Silva D, De Silva H
BMC Pediatr 2018 Sep 24;18(1):308. doi: 10.1186/s12887-018-1286-5. PMID: 30249237Free PMC Article

Diagnosis

Tolonen JP, Parolin Schnekenberg R, McGowan S, Sims D, McEntagart M, Elmslie F, Shears D, Stewart H, Tofaris GK, Dabir T, Morrison PJ, Johnson D, Hadjivassiliou M, Ellard S, Shaw-Smith C, Znaczko A, Dixit A, Suri M, Sarkar A, Harrison RE, Jones G, Houlden H, Ceravolo G, Jarvis J, Williams J, Shanks ME, Clouston P, Rankin J, Blumkin L, Lerman-Sagie T, Ponger P, Raskin S, Granath K, Uusimaa J, Conti H, McCann E, Joss S, Blakes AJM, Metcalfe K, Kingston H, Bertoli M, Kneen R, Lynch SA, Martínez Albaladejo I, Moore AP, Jones WD; Genomics England Research Consortium, Becker EBE, Németh AH
Mov Disord 2024 Jan;39(1):141-151. Epub 2023 Nov 14 doi: 10.1002/mds.29651. PMID: 37964426Free PMC Article
Romaniello R, Pasca L, Panzeri E, D'Abrusco F, Travaglini L, Serpieri V, Signorini S, Aiello C, Bertini E, Bassi MT, Valente EM, Zanni G, Borgatti R, Arrigoni F
Int J Mol Sci 2022 Jun 16;23(12) doi: 10.3390/ijms23126723. PMID: 35743164Free PMC Article
Blanco-Kelly F, Tarilonte M, Villamar M, Damián A, Tamayo A, Moreno-Pelayo MA, Ayuso C, Cortón M
Arch Soc Esp Oftalmol (Engl Ed) 2021 Nov;96 Suppl 1:4-14. Epub 2021 Oct 22 doi: 10.1016/j.oftale.2021.02.002. PMID: 34836588
Rezende Filho FM, Pedroso JL, Freitas JL, Teixeira LF, Barsottini OGP
Arq Neuropsiquiatr 2020 Jun;78(6):383. doi: 10.1590/0004-282X20200013. PMID: 32609195
Ansari M, Rainger J, Hanson IM, Williamson KA, Sharkey F, Harewood L, Sandilands A, Clayton-Smith J, Dollfus H, Bitoun P, Meire F, Fantes J, Franco B, Lorenz B, Taylor DS, Stewart F, Willoughby CE, McEntagart M, Khaw PT, Clericuzio C, Van Maldergem L, Williams D, Newbury-Ecob R, Traboulsi EI, Silva ED, Madlom MM, Goudie DR, Fleck BW, Wieczorek D, Kohlhase J, McTrusty AD, Gardiner C, Yale C, Moore AT, Russell-Eggitt I, Islam L, Lees M, Beales PL, Tuft SJ, Solano JB, Splitt M, Hertz JM, Prescott TE, Shears DJ, Nischal KK, Doco-Fenzy M, Prieur F, Temple IK, Lachlan KL, Damante G, Morrison DA, van Heyningen V, FitzPatrick DR
PLoS One 2016;11(4):e0153757. Epub 2016 Apr 28 doi: 10.1371/journal.pone.0153757. PMID: 27124303Free PMC Article

Prognosis

Keehan L, Jiang MM, Li X, Marom R, Dai H, Murdock D, Liu P, Hunter JV, Heaney JD, Robak L, Emrick L, Lotze T, Blieden LS; Undiagnosed Diseases Network, Lewis RA, Levin AV, Capasso J, Craigen WJ, Rosenfeld JA, Lee B, Burrage LC
Am J Med Genet A 2021 Aug;185(8):2315-2324. Epub 2021 May 5 doi: 10.1002/ajmg.a.62232. PMID: 33949769Free PMC Article
Paganini L, Pesenti C, Milani D, Fontana L, Motta S, Sirchia SM, Scuvera G, Marchisio P, Esposito S, Cinnante CM, Tabano SM, Miozzo MR
Am J Med Genet A 2018 Jun;176(6):1427-1431. Epub 2018 Apr 16 doi: 10.1002/ajmg.a.38704. PMID: 29663667

Clinical prediction guides

Keehan L, Jiang MM, Li X, Marom R, Dai H, Murdock D, Liu P, Hunter JV, Heaney JD, Robak L, Emrick L, Lotze T, Blieden LS; Undiagnosed Diseases Network, Lewis RA, Levin AV, Capasso J, Craigen WJ, Rosenfeld JA, Lee B, Burrage LC
Am J Med Genet A 2021 Aug;185(8):2315-2324. Epub 2021 May 5 doi: 10.1002/ajmg.a.62232. PMID: 33949769Free PMC Article
Paganini L, Pesenti C, Milani D, Fontana L, Motta S, Sirchia SM, Scuvera G, Marchisio P, Esposito S, Cinnante CM, Tabano SM, Miozzo MR
Am J Med Genet A 2018 Jun;176(6):1427-1431. Epub 2018 Apr 16 doi: 10.1002/ajmg.a.38704. PMID: 29663667

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