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Microphthalmia, syndromic 12(MCOPS12)

MedGen UID:
816133
Concept ID:
C3809803
Disease or Syndrome
Synonyms: MCOPS12; MICROPHTHALMIA WITH OR WITHOUT PULMONARY HYPOPLASIA, DIAPHRAGMATIC HERNIA, AND/OR CARDIAC DEFECTS
 
Gene (location): RARB (3p24.2)
 
Monarch Initiative: MONDO:0014229
OMIM®: 615524

Definition

Syndromic microphthalmia-12 is a rare disease characterized by bilateral small eyeballs (microphthalmia), lungs that are too small (pulmonary hypoplasia), and a defect or hole in the diaphragm that allows the abdominal contents to move into the chest cavity (diaphragmatic hernia). Other symptoms may include: Severe global developmental delay with progressive motor impairment due to spasticity and/or uncontrolled repetitive muscular contractions (dystonia), with or without abnormal quick movements that resemble dancing (chorea), Defects of the cerebellum (Chiari type I malformation) Accumulation of cerebrospinal fluid inside the brain (hydrocephaly), Severe feeding difficulties, Mild facial dysmorphism with broad nasal root and tip, and a very small chin (micrognathia), Severe language delay, Wheelchair-bound. Syndromic microphthalmia-12 is caused by mutations in the RARB gene. There is no specific treatment for this syndrome. [from MONDO]

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Bicornuate uterus
MedGen UID:
78599
Concept ID:
C0266387
Congenital Abnormality
The presence of a bicornuate uterus.
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.
Hypoplastic left atrium
MedGen UID:
370300
Concept ID:
C1970625
Anatomical Abnormality
Underdeveloped, small left heart atrium
Intestinal malrotation
MedGen UID:
113153
Concept ID:
C0221210
Congenital Abnormality
An abnormality of the intestinal rotation and fixation that normally occurs during the development of the gut. This can lead to volvulus, or twisting of the intestine that causes obstruction and necrosis.
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.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Congenital diaphragmatic hernia
MedGen UID:
68625
Concept ID:
C0235833
Congenital Abnormality
The presence of a hernia of the diaphragm present at birth.
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.
Broad nasal tip
MedGen UID:
98424
Concept ID:
C0426429
Finding
Increase in width of the nasal tip.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Anophthalmia
MedGen UID:
314
Concept ID:
C0003119
Congenital Abnormality
Absence of the globe or eyeball.
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.

Professional guidelines

PubMed

Delaunay J, Martin L, Bressac-de Paillerets B, Duru G, Ingster O, Thomas L
JAMA Dermatol 2017 Nov 1;153(11):1122-1129. doi: 10.1001/jamadermatol.2017.2926. PMID: 28903138Free PMC Article
Busa T, Legendre M, Bauge M, Quarello E, Bretelle F, Bilan F, Sigaudy S, Gilbert-Dussardier B, Philip N
Prenat Diagn 2016 Jun;36(6):561-7. Epub 2016 May 12 doi: 10.1002/pd.4825. PMID: 27061523
Kondo-Iida E, Kobayashi K, Watanabe M, Sasaki J, Kumagai T, Koide H, Saito K, Osawa M, Nakamura Y, Toda T
Hum Mol Genet 1999 Nov;8(12):2303-9. doi: 10.1093/hmg/8.12.2303. PMID: 10545611

Recent clinical studies

Etiology

Landau-Prat D, Kim DH, Bautista S, Strong A, Revere KE, Katowitz WR, Katowitz JA
Ophthalmic Genet 2023 Dec;44(6):547-552. Epub 2023 Jul 26 doi: 10.1080/13816810.2023.2237568. PMID: 37493047
Alkatan HM, Bedaiwi KM, Al-Faky YH, Maktabi AMY
Sci Rep 2022 Mar 28;12(1):5283. doi: 10.1038/s41598-022-09261-2. PMID: 35347187Free PMC Article
Skalicky SE, White AJ, Grigg JR, Martin F, Smith J, Jones M, Donaldson C, Smith JE, Flaherty M, Jamieson RV
JAMA Ophthalmol 2013 Dec;131(12):1517-24. doi: 10.1001/jamaophthalmol.2013.5305. PMID: 24177921
Wavreille O, François Fiquet C, Abdelwahab O, Laumonier E, Wolber A, Guerreschi P, Pellerin P
Br J Oral Maxillofac Surg 2013 Mar;51(2):e17-21. Epub 2012 Mar 30 doi: 10.1016/j.bjoms.2012.02.018. PMID: 22464758
Allderdice PW, Eales B, Onyett H, Sprague W, Henderson K, Lefeuvre PA, Pal G
Am J Hum Genet 1983 Sep;35(5):1005-19. PMID: 6613995Free PMC Article

Diagnosis

Landau-Prat D, Kim DH, Bautista S, Strong A, Revere KE, Katowitz WR, Katowitz JA
Ophthalmic Genet 2023 Dec;44(6):547-552. Epub 2023 Jul 26 doi: 10.1080/13816810.2023.2237568. PMID: 37493047
Holt R, Goudie D, Verde AD, Gardham A, Ramond F, Putoux A, Sarkar A, Clowes V, Clayton-Smith J, Banka S, Cortazar Galarza L, Thuret G, Ubeda Erviti M, Zurutuza Ibarguren A, Sáez Villaverde R, Tamayo Durán A, Ayuso C, Bax DA, Plaisancie J, Corton M, Chassaing N, Calvas P, Ragge NK
Ophthalmic Genet 2022 Dec;43(6):809-816. doi: 10.1080/13816810.2022.2144905. PMID: 36695497
Kraus C, Uebe S, Thiel CT, Ekici AB, Reis A, Zweier C
Am J Med Genet A 2018 Dec;176(12):2872-2876. Epub 2018 Nov 18 doi: 10.1002/ajmg.a.40640. PMID: 30450806
Couser NL, Masood MM, Aylsworth AS, Stevenson RE
Ophthalmic Genet 2017 Sep-Oct;38(5):401-412. Epub 2017 Jan 23 doi: 10.1080/13816810.2016.1247459. PMID: 28112979
Skalicky SE, White AJ, Grigg JR, Martin F, Smith J, Jones M, Donaldson C, Smith JE, Flaherty M, Jamieson RV
JAMA Ophthalmol 2013 Dec;131(12):1517-24. doi: 10.1001/jamaophthalmol.2013.5305. PMID: 24177921

Therapy

Yoshikawa Y, Yamakawa C, Shimabukuro T, Kinjo H, Fukase S, Oshiro H, Katsuki R, Tome Y, Nishida K
Medicine (Baltimore) 2023 Mar 24;102(12):e33414. doi: 10.1097/MD.0000000000033414. PMID: 36961133Free PMC Article
Schrager NL, Parker SE, Werler MM; for the National Birth Defects Prevention Study
Birth Defects Res 2023 Feb 1;115(3):275-289. Epub 2022 Sep 27 doi: 10.1002/bdr2.2096. PMID: 36168701
Barlinn R, Dudman SG, Rollag H, Trogstad L, Lindstrøm JC, Magnus P
PLoS One 2022;17(12):e0278623. Epub 2022 Dec 1 doi: 10.1371/journal.pone.0278623. PMID: 36455052Free PMC Article
Fish EW, Mendoza-Romero HN, Love CA, Dragicevich CJ, Cannizzo MD, Boschen KE, Hepperla A, Simon JM, Parnell SE
Birth Defects Res 2022 Nov 15;114(19):1229-1243. Epub 2022 Apr 9 doi: 10.1002/bdr2.2009. PMID: 35396933Free PMC Article
Xu YC, Hou JQ, Zhu WJ, Li P
J Cosmet Dermatol 2020 Apr;19(4):789-798. Epub 2019 Nov 7 doi: 10.1111/jocd.13209. PMID: 31697031

Prognosis

Tibrewal S, Subhedar K, Sen P, Mohan A, Singh S, Shah C, Nischal KK, Ganesh S; Bodhya Eye Consortium
Br J Ophthalmol 2021 Jul;105(7):897-903. Epub 2020 Aug 22 doi: 10.1136/bjophthalmol-2020-316910. PMID: 32829301
Lin S, Harlalka GV, Hameed A, Reham HM, Yasin M, Muhammad N, Khan S, Baple EL, Crosby AH, Saleha S
BMC Med Genet 2018 Sep 10;19(1):160. doi: 10.1186/s12881-018-0678-6. PMID: 30200890Free PMC Article
Wavreille O, François Fiquet C, Abdelwahab O, Laumonier E, Wolber A, Guerreschi P, Pellerin P
Br J Oral Maxillofac Surg 2013 Mar;51(2):e17-21. Epub 2012 Mar 30 doi: 10.1016/j.bjoms.2012.02.018. PMID: 22464758
Levine RA, Gray DL, Gould N, Pergament E, Stillerman ML
Ophthalmology 1983 Dec;90(12):1600-3. doi: 10.1016/s0161-6420(83)34345-1. PMID: 6677860
Allderdice PW, Eales B, Onyett H, Sprague W, Henderson K, Lefeuvre PA, Pal G
Am J Hum Genet 1983 Sep;35(5):1005-19. PMID: 6613995Free PMC Article

Clinical prediction guides

Alkatan HM, Bedaiwi KM, Al-Faky YH, Maktabi AMY
Sci Rep 2022 Mar 28;12(1):5283. doi: 10.1038/s41598-022-09261-2. PMID: 35347187Free PMC Article
Indrieri A, Franco B
Genes (Basel) 2021 Feb 11;12(2) doi: 10.3390/genes12020263. PMID: 33670341Free PMC Article
Tibrewal S, Subhedar K, Sen P, Mohan A, Singh S, Shah C, Nischal KK, Ganesh S; Bodhya Eye Consortium
Br J Ophthalmol 2021 Jul;105(7):897-903. Epub 2020 Aug 22 doi: 10.1136/bjophthalmol-2020-316910. PMID: 32829301
Mai CT, Isenburg JL, Canfield MA, Meyer RE, Correa A, Alverson CJ, Lupo PJ, Riehle-Colarusso T, Cho SJ, Aggarwal D, Kirby RS; National Birth Defects Prevention Network
Birth Defects Res 2019 Nov 1;111(18):1420-1435. Epub 2019 Oct 3 doi: 10.1002/bdr2.1589. PMID: 31580536Free PMC Article
Allderdice PW, Eales B, Onyett H, Sprague W, Henderson K, Lefeuvre PA, Pal G
Am J Hum Genet 1983 Sep;35(5):1005-19. PMID: 6613995Free PMC Article

Recent systematic reviews

Marques VM, Santos CS, Santiago IG, Marques SM, Nunes Brasil MDG, Lima TT, Costa PS
Pediatr Neurol 2019 Feb;91:3-10. Epub 2018 Nov 22 doi: 10.1016/j.pediatrneurol.2018.11.003. PMID: 30591235

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