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Corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome(MRXS28)

MedGen UID:
335185
Concept ID:
C1845446
Disease or Syndrome
Synonyms: Agenesis of the Corpus Callosum with Mental Retardation, Ocular Coloboma, and Micrognathia; CORPUS CALLOSUM, AGENESIS OF, WITH IMPAIRED INTELLECTUAL DEVELOPMENT, OCULAR COLOBOMA, AND MICROGNATHIA; MENTAL RETARDATION, X-LINKED, SYNDROMIC 28
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): IGBP1 (Xq13.1)
 
Monarch Initiative: MONDO:0010333
OMIM®: 300472
Orphanet: ORPHA52055

Definition

Corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome is a developmental anomalies syndrome characterized by coloboma of the iris and optic nerve, facial dysmorphism (high forehead, microretrognathia, low-set ears), intellectual deficit, agenesis of the corpus callosum (ACC), sensorineural hearing loss, skeletal anomalies and short stature. [from ORDO]

Clinical features

From HPO
Bilateral cryptorchidism
MedGen UID:
96568
Concept ID:
C0431663
Congenital Abnormality
Absence of both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the scrotum.
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Chronic constipation
MedGen UID:
98325
Concept ID:
C0401149
Sign or Symptom
Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation.
Sensorineural hearing impairment
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Mixed hearing impairment
MedGen UID:
102336
Concept ID:
C0155552
Disease or Syndrome
A type of hearing loss resulting from a combination of conductive hearing impairment and sensorineural hearing impairment.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Lop ear
MedGen UID:
82747
Concept ID:
C0266614
Congenital Abnormality
Anterior and inferior folding of the upper portion of the ear that obliterates triangular fossa and scapha.
Cupped ear
MedGen UID:
335186
Concept ID:
C1845447
Congenital Abnormality
Laterally protruding ear that lacks antihelical folding (including absence of inferior and superior crura).
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
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.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Thoracolumbar scoliosis
MedGen UID:
196671
Concept ID:
C0749379
Anatomical Abnormality
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Recurrent aspiration pneumonia
MedGen UID:
152887
Concept ID:
C0747651
Disease or Syndrome
Increased susceptibility to aspiration pneumonia, defined as pneumonia due to breathing in foreign material, as manifested by a medical history of repeated episodes of aspiration pneumonia.
Choanal atresia
MedGen UID:
3395
Concept ID:
C0008297
Congenital Abnormality
Absence or abnormal closure of the choana (the posterior nasal aperture). Most embryologists believe that posterior choanal atresia results from a failure of rupture between the 35th and 38th day of fetal life of the partition which separates the bucconasal or buccopharyngeal membranes. The resultant choanal atresia may be unilateral or bilateral, bony or membranous, complete or incomplete. In over 90 per cent of cases the obstruction is bony, while in the remainder it is membranous. The bony type of atresia is commonly located 1-2 mm. anterior to the posterior edge of the hard palate, and the osseous septum varies in thickness from 1 to 10 mm. In the membranous form of choanal atresia the obstruction usually occurs further posteriorly. In approximately one third of cases the atresia is bilateral.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Broad forehead
MedGen UID:
338610
Concept ID:
C1849089
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.
Broad neck
MedGen UID:
344099
Concept ID:
C1853638
Finding
Increased side-to-side width of the neck.
Prominent nasal bridge
MedGen UID:
343051
Concept ID:
C1854113
Finding
Anterior positioning of the nasal root in comparison to the usual positioning for age.
Bifid uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.
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.
Coloboma of optic nerve
MedGen UID:
57832
Concept ID:
C0155299
Disease or Syndrome
A cleft of the optic nerve that extends inferiorly.
Iris coloboma
MedGen UID:
116097
Concept ID:
C0240063
Anatomical Abnormality
A coloboma of the iris.
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  
  • CROGVCorpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome
Follow this link to review classifications for Corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome in Orphanet.

Professional guidelines

PubMed

Yu QX, Jing XY, Lin XM, Zhen L, Li DZ
Prenat Diagn 2022 Nov;42(12):1488-1492. Epub 2022 Jul 18 doi: 10.1002/pd.6213. PMID: 35801292
Mandel AM
Handb Clin Neurol 2020;171:291-311. doi: 10.1016/B978-0-444-64239-4.00015-1. PMID: 32736756
De Catte L, De Keersmaeker B, Claus F
Paediatr Drugs 2012 Jun 1;14(3):143-55. doi: 10.2165/11597030-000000000-00000. PMID: 22242843

Recent clinical studies

Etiology

Lanna M, Scelsa B, Cutillo G, Amendolara M, Doneda C, Balestriero M, Faiola S, Casati D, Spaccini L, Cetin I
Ultrasound Obstet Gynecol 2022 Oct;60(4):494-498. doi: 10.1002/uog.24898. PMID: 35274783
Fouda MA, Kim TY, Cohen AR
World Neurosurg 2022 Mar;159:48-53. Epub 2021 Dec 22 doi: 10.1016/j.wneu.2021.12.062. PMID: 34954057
Byrne S, Dionisi-Vici C, Smith L, Gautel M, Jungbluth H
Orphanet J Rare Dis 2016 Feb 29;11:21. doi: 10.1186/s13023-016-0399-x. PMID: 26927810Free PMC Article
Filippi CG, Cauley KA
Semin Ultrasound CT MR 2014 Oct;35(5):445-58. Epub 2014 Jun 24 doi: 10.1053/j.sult.2014.06.004. PMID: 25217298
Garavelli L, Mainardi PC
Orphanet J Rare Dis 2007 Oct 24;2:42. doi: 10.1186/1750-1172-2-42. PMID: 17958891Free PMC Article

Diagnosis

Wright A, Booth R
Dev Med Child Neurol 2023 Sep;65(9):1141-1149. Epub 2023 Feb 3 doi: 10.1111/dmcn.15532. PMID: 36737870
Lanna M, Scelsa B, Cutillo G, Amendolara M, Doneda C, Balestriero M, Faiola S, Casati D, Spaccini L, Cetin I
Ultrasound Obstet Gynecol 2022 Oct;60(4):494-498. doi: 10.1002/uog.24898. PMID: 35274783
Mandel AM
Handb Clin Neurol 2020;171:291-311. doi: 10.1016/B978-0-444-64239-4.00015-1. PMID: 32736756
Olson HE, Demarest ST, Pestana-Knight EM, Swanson LC, Iqbal S, Lal D, Leonard H, Cross JH, Devinsky O, Benke TA
Pediatr Neurol 2019 Aug;97:18-25. Epub 2019 Feb 23 doi: 10.1016/j.pediatrneurol.2019.02.015. PMID: 30928302Free PMC Article
Rennebohm R, Susac JO, Egan RA, Daroff RB
J Neurol Sci 2010 Dec 15;299(1-2):86-91. Epub 2010 Sep 19 doi: 10.1016/j.jns.2010.08.032. PMID: 20855088

Therapy

Frank Y
Pediatr Neurol 2021 Sep;122:59-64. Epub 2021 Jun 16 doi: 10.1016/j.pediatrneurol.2021.06.002. PMID: 34325981
Olson HE, Demarest ST, Pestana-Knight EM, Swanson LC, Iqbal S, Lal D, Leonard H, Cross JH, Devinsky O, Benke TA
Pediatr Neurol 2019 Aug;97:18-25. Epub 2019 Feb 23 doi: 10.1016/j.pediatrneurol.2019.02.015. PMID: 30928302Free PMC Article
Gujral S, Aizenstein H, Reynolds CF 3rd, Butters MA, Erickson KI
Gen Hosp Psychiatry 2017 Nov;49:2-10. doi: 10.1016/j.genhosppsych.2017.04.012. PMID: 29122145Free PMC Article
Dudesek A, Rimmele F, Tesar S, Kolbaske S, Rommer PS, Benecke R, Zettl UK
Clin Exp Immunol 2014 Mar;175(3):385-96. doi: 10.1111/cei.12204. PMID: 24028073Free PMC Article
Rennebohm R, Susac JO, Egan RA, Daroff RB
J Neurol Sci 2010 Dec 15;299(1-2):86-91. Epub 2010 Sep 19 doi: 10.1016/j.jns.2010.08.032. PMID: 20855088

Prognosis

Jańczewska I, Preis-Orlikowska J, Domżalska-Popadiuk I, Preis K, Jańczewska A
Neurol Neurochir Pol 2023;57(3):269-281. Epub 2023 Apr 20 doi: 10.5603/PJNNS.a2023.0026. PMID: 37078131
Mandel AM
Handb Clin Neurol 2020;171:291-311. doi: 10.1016/B978-0-444-64239-4.00015-1. PMID: 32736756
Alrakaf L, Al-Owain MA, Busehail M, Alotaibi MA, Monies D, Aldhalaan HM, Alhashem A, Al-Hassnan ZN, Rahbeeni ZA, Murshedi FA, Ani NA, Al-Maawali A, Ibrahim NA, Abdulwahab FM, Alsagob M, Hashem MO, Ramadan W, Abouelhoda M, Meyer BF, Kaya N, Maddirevula S, Alkuraya FS
Am J Med Genet A 2018 Mar;176(3):715-721. Epub 2018 Jan 31 doi: 10.1002/ajmg.a.38615. PMID: 29383837
Volpe P, Campobasso G, De Robertis V, Rembouskos G
Prenat Diagn 2009 Apr;29(4):340-54. doi: 10.1002/pd.2208. PMID: 19184971
Garavelli L, Mainardi PC
Orphanet J Rare Dis 2007 Oct 24;2:42. doi: 10.1186/1750-1172-2-42. PMID: 17958891Free PMC Article

Clinical prediction guides

Jańczewska I, Preis-Orlikowska J, Domżalska-Popadiuk I, Preis K, Jańczewska A
Neurol Neurochir Pol 2023;57(3):269-281. Epub 2023 Apr 20 doi: 10.5603/PJNNS.a2023.0026. PMID: 37078131
Kızıltunç PB, Şahlı E, İdil A, Atilla H
Turk J Pediatr 2021;63(2):291-299. doi: 10.24953/turkjped.2021.02.013. PMID: 33929119
Tripathy R, Leca I, van Dijk T, Weiss J, van Bon BW, Sergaki MC, Gstrein T, Breuss M, Tian G, Bahi-Buisson N, Paciorkowski AR, Pagnamenta AT, Wenninger-Weinzierl A, Martinez-Reza MF, Landler L, Lise S, Taylor JC, Terrone G, Vitiello G, Del Giudice E, Brunetti-Pierri N, D'Amico A, Reymond A, Voisin N, Bernstein JA, Farrelly E, Kini U, Leonard TA, Valence S, Burglen L, Armstrong L, Hiatt SM, Cooper GM, Aldinger KA, Dobyns WB, Mirzaa G, Pierson TM, Baas F, Chelly J, Cowan NJ, Keays DA
Neuron 2018 Dec 19;100(6):1354-1368.e5. Epub 2018 Nov 15 doi: 10.1016/j.neuron.2018.10.044. PMID: 30449657Free PMC Article
Alrakaf L, Al-Owain MA, Busehail M, Alotaibi MA, Monies D, Aldhalaan HM, Alhashem A, Al-Hassnan ZN, Rahbeeni ZA, Murshedi FA, Ani NA, Al-Maawali A, Ibrahim NA, Abdulwahab FM, Alsagob M, Hashem MO, Ramadan W, Abouelhoda M, Meyer BF, Kaya N, Maddirevula S, Alkuraya FS
Am J Med Genet A 2018 Mar;176(3):715-721. Epub 2018 Jan 31 doi: 10.1002/ajmg.a.38615. PMID: 29383837
Garavelli L, Mainardi PC
Orphanet J Rare Dis 2007 Oct 24;2:42. doi: 10.1186/1750-1172-2-42. PMID: 17958891Free PMC Article

Recent systematic reviews

Ferreira Soares D, Pires de Aguiar PH
Neuromodulation 2023 Apr;26(3):518-528. Epub 2022 Aug 19 doi: 10.1016/j.neurom.2022.06.005. PMID: 35989160
Awad AJ, Kaiser KN
Seizure 2022 Mar;96:137-141. Epub 2022 Feb 6 doi: 10.1016/j.seizure.2022.02.002. PMID: 35245877
Joigneau Prieto L, Ruiz Y, Pérez R, De León Luis J
Eur J Paediatr Neurol 2019 Nov;23(6):764-782. Epub 2019 Sep 25 doi: 10.1016/j.ejpn.2019.09.009. PMID: 31587959
Renkema RW, Caron CJJM, Wolvius EB, Dunaway DJ, Forrest CR, Padwa BL, Koudstaal MJ
Int J Oral Maxillofac Surg 2018 Jan;47(1):27-34. Epub 2017 Jul 20 doi: 10.1016/j.ijom.2017.06.009. PMID: 28736116
Graham D, Tisdall MM, Gill D
Epilepsia 2016 Jul;57(7):1053-68. Epub 2016 May 29 doi: 10.1111/epi.13408. PMID: 27237542

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