Table 2.
Summary of all studies included in the review.
| Author | Publication Year | Design | Evidence Level | N | Agea | Genetic Findingsb | Neurological Findingsc | Ocular Findings |
|---|---|---|---|---|---|---|---|---|
| Adkins et al. [55] | 1979 | Case report | E | 1 | 14 m | Not reported | Aprosencephaly | Rieger anomaly |
| Aldinger et al. [15] | 2009 | Case series | D | 21 | Not reported | FOXC1 | Dandy-Walker, cerebellar vermis hypoplasia, mega-cisterna magna, white matter hyperintensities, partial agenesis of the corpus callosum | Anterior segment dysgenesis |
| Ali et al. [51] | 2018 | Case report | E | 1 | 3 d | FGFR | Partial agenesis of the corpus callosum | Axenfeld's anomaly |
| Avasarala et al. [16] | 2018 | Case report | E | 2 | 20 y | FOXC1 | White matter hyperintensities | None |
| Awan et al. [56] | 1977 | Case report | E | 1 | 19 y | Not reported | Tilted optic disc, inferiorly displaced macula, dysversion and hypoplasia of optic disc | Rieger's anomaly |
| Balasubramanian et al. [17] | 2012 | Case report | E | 1 | 5 y | FOXC1 | White matter tigroid pattern, polymicrogyria, hypoplasia of the cerebellum, corpus callosum, and brainstem | Posterior embryotoxon, iris adhesions to cornea |
| Barkana et al. [57] | 2012 | Case report | E | 2 | 3 y | Not reported | Subcortical white matter lesions | Posterior embryotoxon |
| Beby et al. [18] | 2012 | Case report | E | 1 | 26 y | FOXC1 | Dandy-Walker, optic disc coloboma | Posterior embryotoxon, corectopia |
| Bellenguez et al. [14] | 2012 | GWAS | D | 9520 | Not reported | PITX2 | Stroke | None |
| Bozza et al. [19] | 2013 | Case report | E | 2 | 6 y | FOXC1 | Increase of R peri-frontal subarachnoid space, shallow sulci | None |
| Breningstall et al. [20] | 2017 | Case report | E | 1 | 27 m | FOXC1 | White matter hyperintensities, ventriculomegaly | Posterior embryotoxon, iris adhesions to cornea |
| Caluseriu et al. [21] | 2006 | Case report | E | 1 | 36 y | FOXC1 | Subcortical atrophy, periventricular white matter attenuation | Posterior embryotoxon, iris atrophy |
| Cellini et al. [22] | 2012 | Case report | E | 2 | 8–25 y | FOXC1 | White matter hyperintensities, supratentorial atrophy, mega-cisterna magna, cerebellar hypoplasia | None |
| Cok et al. [58] | 2005 | Case report | E | 1 | 6 y | Not reported | Suprasellar arachnoid cyst | Axenfeld Rieger |
| Corona-Rivera et al. [23] | 2018 | Case report | E | 1 | 3 m | FOXC1 | Mild frontal lobe atrophy, colpocephaly | Posterior embryotoxon, corectopia, iris hypoplasia |
| Coupry et al. [3] | 2010 | Case report | E | 2 | 8–58 y | COL4A1 | Periventricular leukoencephalopathy | Posterior embryotoxon |
| Davies et al. [24] | 1999 | Case report | E | 2 | 9–20 y | FOXC1 | Hydrocephalus, died of intracranial HTN, macrocephaly, cerebral atrophy | Coloboma |
| Delahaye et al. [25] | 2012 | Case series | D | 5 | Prenatal (18w gestation) –27 y | FOXC1 | Vermis hypoplasia, white matter hyperintensities, mega-cisterna magna | Schwalbe's Ring, corectopia Axenfeld anomaly |
| DeScipio et al. [26] | 2005 | Case series | D | 5 | 27w–10 y | FOXC1 | Posterior fossa cyst, polymicroglia, Dandy-Walker | Posterior embryotoxon |
| Eid et al. [27] | 2020 | Case report | E | 1 | 9 m | FOXC1 | Leukoencephalopathy, cavum septum pellucidum, polymicrogyria, occipital pachygyria | None |
| Fan et al. [28] | 2020 | Case report | E | 2 | 24–53 y | FOXC1 | White matter hyperintensities, basal ganglia calcifications | Posterior embryotoxon |
| French et al. [4] | 2014 | Case series, GWAS | D | 18 | 1 y | FOXC1 & PITX2 | Cerebral small vessel disease (white matter hyperintensities, dilated perivascular spaces, lacunar infarcts) | None |
| Gould et al. [29] | 2004 | Case report | E | 4 | Not reported | FOXC1 | Dandy-Walker, agenesis of the corpus callosum and brainstem | Rieger anomaly |
| Idrees et al. [13] | 2006 | Case series | D | 3 | 16–64 y | PITX2 | Enlarged cisterna magna, flattened sella turcica | Posterior embryotoxon, corectopia |
| Kapoor et al. [76] | 2011 | Case report | E | 1 | 6 y | FOXC1 | Demyelination of subcortical and periventricular white matter | Posterior embryotoxon, corectopia |
| Kearns et al. [31] | 2019 | Case series | E | 2 | 6–11 y | FOXC1 | Enlarged perivascular spaces, white matter hyperintensities, shortened corpus callosum, short vermis, mega cisterna magna, arterial tortuosity, dolichoectasia of vertebrobasilar system, enlargement of occipital horns of lateral ventricles | None |
| Kerrigan et al. [69] | 2007 | Case report | E | 1 | 8.6 y | FOXC1 | Microcephaly at birth, hypothalamic hamartoma | None |
| Kleinmann et al. [59] | 1981 | Case series | D | 7 | 2w– 41 + y | Not reported | Enlarged sella | Rieger's anomaly |
| Koçak-Midillioglu et al. [77] | 2003 | Case report | E | 1 | Birth | Not reported | Indistinctness of margins of optic disc, elevated optic nerve head surface, yellow-pink disc, optic nerve drusen | Axenfeld Rieger |
| Kumar et al. [32] | 2017 | Case report | E | 1 | 8 y | FOXC1 | Leukoencephalopathy | Axenfeld Rieger |
| Levin et al. [33] | 1986 | Case report | E | 1 | 5w | FOXC1 | Hydrocephalus | Axenfeld Rieger |
| Linhares et al. [34] | 2015 | Case report | E | 1 | 12 y | FOXC1 | Diffuse leukopathy, CSF fistula (CSF rhinorrhea) | Corectopia |
| Lopes et al. [35] | 2019 | Case report | E | 1 | Not reported | FOXC1 | White matter hyperintensities, intracranial calcifications | Posterior embryotoxon |
| Lowry et al. [68] | 2007 | Case report | E | 1 | 23 y | Normal for FOXC1, PITX2, & BARX1 | De Hauwere syndrome (Axenfeld Rieger, hydrocephalus, hearing loss) | |
| Maclean et al. [36] | 2005 | Case report | E | 1 | 22 m | FOXC1 | Hydrocephalus; hypoplasia of the cerebellum, brainstem, and corpus callosum | Axenfeld Rieger |
| Martinez-glez et al. [37] | 2006 | Case report | E | 1 | 22 y | FOXC1 | Hydrocephalus | None |
| McCann et al. [52] | 2005 | Case report | E | 1 | 3w | FGFR | Scaphocephaly, Chiari I | Axenfeld Rieger |
| Megighian et al. [62] | 2003 | Case report | E | 1 | 32 y | Not reported | Dysmorphism of the acoustic channels | Bilateral dysgenesis of the iris |
| Meuwissen et al. [46] | 2015 | Case series | D | 24 | Not reported | COL4A1 | Periventricular leukomalacia | Posterior embryotoxon |
| Moog et al. [61] | 1998 | Case report | E | 2 | 35–39 y | Not reported | Hydrocephalus, leptomeningeal calcifications | Axenfeld Rieger |
| Nandeesh et al. [47] | 2020 | Case report | E | 1 | 18 y | COL4A1 | Leukoencephalopathy, microhemorrhagic lesions, hemorrhagic stroke, porencephalic cyst, right vertebral dolichoectasia | Axenfeld Rieger |
| Nastasi et al. [63] | 2018 | Case report | E | 1 | 1w | Not reported | Occipital-cervical meningocele, ventriculomegaly | Posterior embryotoxon |
| Nielsen et al. [54] | 1984 | Case report | E | 1 | 4 m |
21q22.2 Monosomy |
Cerebral atrophy | Posterior embryotoxon |
| Pace et al. [38] | 2017 | Case report | E | 1 | 49 y | FOXC1 | Microcephaly | None |
| Puklin et al. [64] | 1981 | Case report | E | 1 | 6w | Not reported | Elevated optic discs with blurred margins and slight pallor | Axenfeld anomaly |
| Reis et al. [53] | 2011 | Case series | D | 1 | 6 y | BMP4 | Macrocephaly | Rieger anomaly |
| Rodahl et al. [48] | 2013 | Case series | D | 45 | Birth–90 y | COL4A1 | Cerebral hemorrhages, leukoencephaly, calcifications, ventriculomegaly, cerebellar atrophy | Iris hypoplasia, posterior embryotoxon, corectopia, peripheral anterior synechiae |
| Saffari et al. [39] | 2020 | Case report | E | 2 | Adolescent | FOXC1 & COL4A1 | White matter hyperintensities | Axenfeld Rieger |
| Schumann et al. [40] | 2016 | Case control | C | 4 | Prenatal | FOXC1 | Dandy-Walker, ventriculomegaly | None |
| Shah et al. [50] | 2012 | Case report | E | 1 | Birth | COL4A1 | Periventricular white matter change, progressive microcephaly | Anterior segment dysgenesis |
| Shields et al. [2] | 1983 | Case series | D | 5 | 15–50 y | Not reported | Empty sella, parasellar arachnoid cyst |
|
| Sibon et al. [49] | 2007 | Case report | E | 5 | 8–58 y | COL4A1 | Leukoencephalopathy | Axenfeld Rieger |
| Steinsapir et al. [65] | 1990 | Case report | E | 1 | Birth | Not reported | Brachycephalic skull, spina Bifida occulta | Rieger's anomaly |
| Titheradge et al. [12] | 2014 | Case report | E | 4 | 4–40 y | PITX2 | Microcephaly, optic nerve drusen | Posterior embryotoxon, peripheral anterior synechiae |
| Van Bever et al. [67] | 2007 | Case report | E | 1 | Birth | Normal for PAX6, FOXC1, PITX2, & MYNC | Microcephaly, occipito-temporal hematoma | Iris adhesions to cornea |
| Van Daele et al. [66] | 1996 | Case report | E | 1 | Birth | Not reported | Enlarged frontal and temporoparietal subarachnoid spaces | Axenfeld anomaly |
| Van Der Knaap et al. [41] | 2006 | Case report | E | 3 | 1–2 y | FOXC1 | White matter hyperintensities, white matter tigroid pattern | Posterior embryotoxon |
| Vernon et al. [42] | 2013 | Case report | E | 1 | 41 y | FOXC1 | Leukoencephalopathy | Axenfeld Rieger |
| Whitehead et al. [6] | 2013 | Case report | E | 1 | 19 m | Not reported | Deep periventricular white lesions, pineal and pars intermedia cysts | Axenfeld Rieger |
| Wu et al. [43] | 2020 | Case series | D | 11 | Not reported | FOXC1 | AVM | Axenfeld Rieger |
| Yararbas et al. [44] | 2019 | Case report | E | 1 | 2.5 y | FOXC1 | Cystic cisterna magna, macrocephaly, ventricular dilatation | None |
| Zhang et al. [45] | 2004 | Case report | E | 1 | Birth | FOXC1 | Cortical atrophy, cerebellar hypoplasia, brachycephaly, microcephaly | None |
| Zhao et al. [11] | 2022 | Case control | C | 977 | = 64 y | PITX2 | Stroke | None |
a
d = days, w = weeks, m = months, y = years.
b
FOXC1 = forkhead box protein C1, COL4A1 = collagen type IV alpha 1, PITX2 = pituitary homeobox 2, FGFR = fibroblast growth factor receptor, BMP4 = bone morphogenetic protein 4.
c
HTN = hypertension, CSF = cerebrospinal fluid, AVM = arteriovenous malformation.