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Gastrointestinal defects and immunodeficiency syndrome 2(GIDID2)

MedGen UID:
1811526
Concept ID:
C5676901
Disease or Syndrome
Synonyms: GIDID2; MULTIPLE INTESTINAL ATRESIA WITH OR WITHOUT LEUKOPENIA
 
Gene (location): PI4KA (22q11.21)
 
Monarch Initiative: MONDO:0030669
OMIM®: 619708

Disease characteristics

Excerpted from the GeneReview: PI4KA-Related Disorder
PI4KA-related disorder is a clinically variable disorder characterized primarily by neurologic dysfunction (limb spasticity, developmental delay, intellectual disability, seizures, ataxia, nystagmus), gastrointestinal manifestations (multiple intestinal atresia, inflammatory bowel disease), and combined immunodeficiency (leukopenia, variable immunoglobulin defects). Age of onset is typically antenatal or in early childhood; individuals can present with any combination of these features. Rare individuals present with later-onset hereditary spastic paraplegia. Brain MRI findings can include hypomyelinating leukodystrophy, cerebellar hypoplasia/atrophy, thin or dysplastic corpus callosum, and/or perisylvian polymicrogyria. [from GeneReviews]
Authors:
Emma L Baple  |  Claire Salter  |  Holm Uhlig, et. al.   view full author information

Additional description

From OMIM
Gastrointestinal defects and immunodeficiency syndrome-2 (GIDID2) is a severe autosomal recessive developmental disorder characterized by multiple intestinal atresia apparent soon after birth. Affected infants have a distended abdomen and do not pass meconium. There is some evidence of inflammatory bowel disease. Death occurs in the first weeks of life. Some patients may also have immunodeficiency (summary by Salter et al., 2021). For a discussion of genetic heterogeneity of GIDID, see GIDID1 (243150).  http://www.omim.org/entry/619708

Clinical features

From HPO
Dilatation of the renal pelvis
MedGen UID:
574571
Concept ID:
C0341676
Disease or Syndrome
The presence of dilatation of the renal pelvis.
Knee flexion contracture
MedGen UID:
98042
Concept ID:
C0409355
Finding
A type of knee joint contracture in which the knee is in a fixed bent (flexed) configuration such that it cannot be straightened actively or passively.
Overlapping fingers
MedGen UID:
252954
Concept ID:
C1446712
Finding
A finger resting on the dorsal surface of an adjacent digit when the hand is at rest.
Bilateral talipes equinovarus
MedGen UID:
332956
Concept ID:
C1837835
Congenital Abnormality
Bilateral clubfoot deformity.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Intestinal atresia
MedGen UID:
7129
Concept ID:
C0021828
Disease or Syndrome
An abnormal closure, or atresia of the tubular structure of the intestine.
Rectovaginal fistula
MedGen UID:
11152
Concept ID:
C0034895
Finding
The presence of a fistula between the vagina and the rectum.
Inflammation of the large intestine
MedGen UID:
662273
Concept ID:
C0578878
Disease or Syndrome
Inflammation, or an inflammatory state in the large intestine.
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).
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Leukodystrophy
MedGen UID:
6070
Concept ID:
C0023520
Disease or Syndrome
Leukodystrophy refers to deterioration of white matter of the brain resulting from degeneration of myelin sheaths in the CNS. Their basic defect is directly related to the synthesis and maintenance of myelin membranes. Symmetric white matter involvement at MRI is a typical finding in patients with leukodystrophies.
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.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Polymicrogyria
MedGen UID:
78605
Concept ID:
C0266464
Congenital Abnormality
Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds).
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.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
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.
Head titubation
MedGen UID:
299071
Concept ID:
C1608410
Sign or Symptom
A head tremor of moderate speed (3 to 4 Hz) in the anterior-posterior direction.
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.
Hypoplasia of the pons
MedGen UID:
341246
Concept ID:
C1848529
Finding
Underdevelopment of the pons.
Hyperintensity of cerebral white matter on MRI
MedGen UID:
811125
Concept ID:
C2938912
Pathologic Function
A brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter.
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.
Delayed fine motor development
MedGen UID:
869257
Concept ID:
C4023681
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the fingers and hands.
CNS hypomyelination
MedGen UID:
892446
Concept ID:
C4025616
Finding
Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis.
Intention tremor
MedGen UID:
1642960
Concept ID:
C4551520
Sign or Symptom
A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger).
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.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Dolichocephaly
MedGen UID:
65142
Concept ID:
C0221358
Congenital Abnormality
An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.
Bronchiectasis
MedGen UID:
14234
Concept ID:
C0006267
Disease or Syndrome
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
Pulmonary hypoplasia
MedGen UID:
78574
Concept ID:
C0265783
Congenital Abnormality
A congenital abnormality in which the lung parenchyma is not fully developed. It may be associated with other congenital abnormalities.
Interstitial emphysema
MedGen UID:
234586
Concept ID:
C1370824
Disease or Syndrome
Interstitial emphysema is characterized by air dissecting within the interstitium of the lung, typically in the peribronchovascular sheaths, interlobular septa, and visceral pleura. It is most commonly seen in neonates receiving mechanical ventilation. It is rarely recognized radiographically in adults and is infrequently seen on CT scans. It appears as perivascular lucent or low attenuating halos and small cysts.
Immunodeficiency
MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Absent uvula
MedGen UID:
75599
Concept ID:
C0266121
Congenital Abnormality
Lack of the uvula.
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.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Esodeviation
MedGen UID:
1641033
Concept ID:
C4551734
Disease or Syndrome
A manifest or latent ocular deviation in which one or both eyes tends to deviate nasally.

Term Hierarchy

Professional guidelines

PubMed

Ebo DG, Verweij MM, De Knop KJ, Hagendorens MM, Bridts CH, De Clerck LS, Stevens WJ
Paediatr Drugs 2010 Aug 1;12(4):257-68. doi: 10.2165/11532590-000000000-00000. PMID: 20593909
Al-Muhsen SZ
Saudi J Gastroenterol 2010 Apr-Jun;16(2):66-74. doi: 10.4103/1319-3767.61230. PMID: 20339173Free PMC Article
Yunis NA, Stone VE
J Acquir Immune Defic Syndr Hum Retrovirol 1998 Jun 1;18(2):145-54. doi: 10.1097/00042560-199806010-00006. PMID: 9637579

Recent clinical studies

Etiology

Chandrasekaran P, Han Y, Zerbe CS, Heller T, DeRavin SS, Kreuzberg SA, Marciano BE, Siu Y, Jones DR, Abraham RS, Stephens MC, Tsou AM, Snapper S, Conlan S, Subramanian P, Quinones M, Grou C, Calderon V, Deming C, Leiding JW, Arnold DE, Logan BR, Griffith LM, Petrovic A, Mousallem TI, Kapoor N, Heimall JR, Barnum JL, Kapadia M, Wright N, Rayes A, Chandra S, Broglie LA, Chellapandian D, Deal CL, Grunebaum E, Lim SS, Mallhi K, Marsh RA, Murguia-Favela L, Parikh S, Touzot F, Cowan MJ, Dvorak CC, Haddad E, Kohn DB, Notarangelo LD, Pai SY, Puck JM, Pulsipher MA, Torgerson TR, Kang EM, Malech HL, Segre JA, Bryant CE, Holland SM, Falcone EL
J Allergy Clin Immunol 2023 Dec;152(6):1619-1633.e11. Epub 2023 Sep 1 doi: 10.1016/j.jaci.2023.07.022. PMID: 37659505
Urschel D, Hernandez-Trujillo VP
Clin Rev Allergy Immunol 2022 Aug;63(1):99-105. Epub 2022 Feb 8 doi: 10.1007/s12016-022-08927-z. PMID: 35133619
Proper SP, Lavery WJ, Bernstein JA
Allergy Asthma Proc 2020 Nov 1;41(Suppl 1):S03-S07. doi: 10.2500/aap.2020.41.200040. PMID: 33109317
Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, Akdis CA, Gao YD
Allergy 2020 Jul;75(7):1730-1741. Epub 2020 Feb 27 doi: 10.1111/all.14238. PMID: 32077115
Goldmuntz E
Am J Med Genet C Semin Med Genet 2020 Mar;184(1):64-72. Epub 2020 Feb 12 doi: 10.1002/ajmg.c.31774. PMID: 32049433

Diagnosis

Denkboy Öngen Y, Özemri Sağ Ş, Temel ŞG, Eren E
J Clin Res Pediatr Endocrinol 2023 Aug 23;15(3):285-292. Epub 2023 Apr 19 doi: 10.4274/jcrpe.galenos.2023.2022-11-3. PMID: 37074225Free PMC Article
Urschel D, Hernandez-Trujillo VP
Clin Rev Allergy Immunol 2022 Aug;63(1):99-105. Epub 2022 Feb 8 doi: 10.1007/s12016-022-08927-z. PMID: 35133619
Proper SP, Lavery WJ, Bernstein JA
Allergy Asthma Proc 2020 Nov 1;41(Suppl 1):S03-S07. doi: 10.2500/aap.2020.41.200040. PMID: 33109317
Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, Akdis CA, Gao YD
Allergy 2020 Jul;75(7):1730-1741. Epub 2020 Feb 27 doi: 10.1111/all.14238. PMID: 32077115
McDonald-McGinn DM, Sullivan KE, Marino B, Philip N, Swillen A, Vorstman JA, Zackai EH, Emanuel BS, Vermeesch JR, Morrow BE, Scambler PJ, Bassett AS
Nat Rev Dis Primers 2015 Nov 19;1:15071. doi: 10.1038/nrdp.2015.71. PMID: 27189754Free PMC Article

Therapy

Cattalini M, Della Paolera S, Zunica F, Bracaglia C, Giangreco M, Verdoni L, Meini A, Sottile R, Caorsi R, Zuccotti G, Fabi M, Montin D, Meneghel A, Consolaro A, Dellepiane RM, Maggio MC, La Torre F, Marchesi A, Simonini G, Villani A, Cimaz R, Ravelli A, Taddio A; Rheumatology Study Group of the Italian Pediatric Society
Pediatr Rheumatol Online J 2021 Mar 16;19(1):29. doi: 10.1186/s12969-021-00511-7. PMID: 33726806Free PMC Article
Bai JC, Mazure RM, Vazquez H, Niveloni SI, Smecuol E, Pedreira S, Mauriño E
Clin Gastroenterol Hepatol 2004 Oct;2(10):849-60. doi: 10.1016/s1542-3565(04)00387-8. PMID: 15476147
Bousvaros A, Mueller B
Drugs 2001;61(6):777-87. doi: 10.2165/00003495-200161060-00006. PMID: 11398909
Vella S, Floridia M
Clin Pharmacokinet 1998 Mar;34(3):189-201. doi: 10.2165/00003088-199834030-00002. PMID: 9533981
Beal J, Flynn N
J Physicians Assoc AIDS Care 1995 Jan;2(1):19-22. PMID: 11362196

Prognosis

Giardino S, Volpi S, Lucioni F, Caorsi R, Schneiderman J, Lang A, Khojah A, Kuijpers T, Papadatou I, Paisiou A, Alonso L, Schulz A, Marcus N, Gattorno M, Faraci M
J Clin Immunol 2022 Oct;42(7):1535-1544. Epub 2022 Jun 29 doi: 10.1007/s10875-022-01305-6. PMID: 35767111
Swillen A, McDonald-McGinn D
Am J Med Genet C Semin Med Genet 2015 Jun;169(2):172-81. Epub 2015 May 18 doi: 10.1002/ajmg.c.31435. PMID: 25989227Free PMC Article
Cunningham-Rundles C
Hematology Am Soc Hematol Educ Program 2012;2012:301-5. doi: 10.1182/asheducation-2012.1.301. PMID: 23233596Free PMC Article
Al-Muhsen SZ
Saudi J Gastroenterol 2010 Apr-Jun;16(2):66-74. doi: 10.4103/1319-3767.61230. PMID: 20339173Free PMC Article
Bai JC, Mazure RM, Vazquez H, Niveloni SI, Smecuol E, Pedreira S, Mauriño E
Clin Gastroenterol Hepatol 2004 Oct;2(10):849-60. doi: 10.1016/s1542-3565(04)00387-8. PMID: 15476147

Clinical prediction guides

Chandrasekaran P, Han Y, Zerbe CS, Heller T, DeRavin SS, Kreuzberg SA, Marciano BE, Siu Y, Jones DR, Abraham RS, Stephens MC, Tsou AM, Snapper S, Conlan S, Subramanian P, Quinones M, Grou C, Calderon V, Deming C, Leiding JW, Arnold DE, Logan BR, Griffith LM, Petrovic A, Mousallem TI, Kapoor N, Heimall JR, Barnum JL, Kapadia M, Wright N, Rayes A, Chandra S, Broglie LA, Chellapandian D, Deal CL, Grunebaum E, Lim SS, Mallhi K, Marsh RA, Murguia-Favela L, Parikh S, Touzot F, Cowan MJ, Dvorak CC, Haddad E, Kohn DB, Notarangelo LD, Pai SY, Puck JM, Pulsipher MA, Torgerson TR, Kang EM, Malech HL, Segre JA, Bryant CE, Holland SM, Falcone EL
J Allergy Clin Immunol 2023 Dec;152(6):1619-1633.e11. Epub 2023 Sep 1 doi: 10.1016/j.jaci.2023.07.022. PMID: 37659505
Denkboy Öngen Y, Özemri Sağ Ş, Temel ŞG, Eren E
J Clin Res Pediatr Endocrinol 2023 Aug 23;15(3):285-292. Epub 2023 Apr 19 doi: 10.4274/jcrpe.galenos.2023.2022-11-3. PMID: 37074225Free PMC Article
Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, Akdis CA, Gao YD
Allergy 2020 Jul;75(7):1730-1741. Epub 2020 Feb 27 doi: 10.1111/all.14238. PMID: 32077115
Cagdas D, Gur Cetinkaya P, Karaatmaca B, Esenboga S, Tan C, Yılmaz T, Gümüş E, Barış S, Kuşkonmaz B, Ozgur TT, Bali P, Santisteban I, Orhan D, Yüce A, Cetinkaya D, Boztug K, Hershfield M, Sanal O, Tezcan İ
J Clin Immunol 2018 May;38(4):484-493. Epub 2018 May 9 doi: 10.1007/s10875-018-0496-9. PMID: 29744787
Swillen A, McDonald-McGinn D
Am J Med Genet C Semin Med Genet 2015 Jun;169(2):172-81. Epub 2015 May 18 doi: 10.1002/ajmg.c.31435. PMID: 25989227Free PMC Article

Recent systematic reviews

Mauracher AA, Gujer E, Bachmann LM, Güsewell S, Pachlopnik Schmid J
J Allergy Clin Immunol Pract 2021 Feb;9(2):792-802.e10. Epub 2020 Nov 11 doi: 10.1016/j.jaip.2020.10.057. PMID: 33186766

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