Table 1.
Updated list of NR2F1 variants and clinical description of BBSOAS reported patients. BBSOAS patients, identified by their protein variant and—when available—by their LOVD identifier, are listed following the chronological order of reports and publications describing their cases. Main clinical signs include altered brain morphology as observed by MRI, developmental delay (DD), intellectual disability (ID), visual system deficits, early-onset epilepsy and seizures (EOE/S), autism spectrum disorder (ASD) and behavioral abnormalities and hypotonia. The severity index of each patient has been calculated based on the presence/absence of the main clinical signs, ranging from 1 (one symptom category only found in the patient) to a maximum of 7 (all listed clinical signs are present, to different extent, in the same patient). An extended version of these data, with additional columns describing other less common clinical features, is available in Supplementary Table S1. List of references: AK13, Al-Kateb et al., 2013; BA19, Balciuniene et al., 2019; BE18, Bertacchi et al., 2018; BE20, Bertacchi et al., 2020; BR09, Brown et al., 2009; CA09, Cardoso et al., 2009; BO14, Bosch et al., 2014; BO20, Bojanek et al., 2020; CH16, Chen et al., 2016; DI16, Dimassi et al., 2016; EL17, Eldomery et al., 2017; GA21, Gazdagh et al., 2021; HF15, Hino-Fukuyo et al., 2015; HF17, Hino-Fukuyo et al., 2017; HO20, Hobbs et al., 2020; JS20, Jezela-Stanek et al., 2020; JU21, Jurkute, Bertacchi et al., 2021; KA17, Kaiwar et al., 2017; MH18, Martín-Hernández et al., 2018; MI14, Michaud et al., 2014; MI20, Mio et al., 2020; PA19, Park et al., 2019; SA13, Sanders et al., 2013; ST20, Starosta et al., 2020; RE20, Rech et al., 2020; RO20, Rochtus et al., 2020; VI17, Vissers et al., 2017; WA20 Walsh et al., 2020; ZO20, Zou et al., 2020. Abbreviations: CB, cerebellum; CC, corpus callosum; CS, corticospinal tract; D, deletion; DBD, DNA binding domain; DD, developmental delay; DM, delayed myelination; DMD, delayed motor development/poor coordination; DQ, developmental quotient; EOE/S, early-onset epilepsy/seizures; FI/NFI, frameshifting indel/non frameshifting indel; FS, febrile seizures; GCL, ganglionic cell layer; GVI, general visual impairments; HP, hippocampus; HPM, hippocampal malrotation; ID, intellectual disability; IQ, intelligence quotient; IS, infantile spasms; LBD, ligand binding domain; LV, lateral ventricle; LVA, low visual acuity; MCP, macrocephaly; MD, microdeletion; MM, missense mutation; OA, optic atrophy; OC, optic chiasm; OCB/RB, obsessive-compulsive/repetitive behaviors; OD, optic disc; ON, optic nerve; ONH, ON hypoplasia; P/SOD, pale/small optic disc; PDD-NOS, pervasive developmental disorder—not otherwise specified; PH, bilateral periventricular heterotopia; RB, repetitive behavior; RNFL, retinal nerve fiber layer; TIV, translation initiation variants; WGD, whole-gene deletion; WM, white matter. For the extended report, please refer to Supplementary Table S1.
| References | LOVD Database ID; Patient ID | Variant Type | Variant (Protein) | MRI (General; Optic Nerve and Cortical Morphology) | DD | ID | Visual System Defect(s) and Visual Deficit | EOE/S | ASD Behavioral Abnormalities | Hypotonia | Severity Index |
|---|---|---|---|---|---|---|---|---|---|---|---|
| BR09 | BE18, #1 | De novo deletion (400–500 Kb MD at breakpoints following paracentric inversion) | Deleted | Cranial nerve abnormalities | Yes | ND | ND | ND | ND | Yes | 3 |
| CA09 | BE18, #2 | De novo deletion | Deleted | PH | Yes | Yes; speech delay | Coloboma | FS | ND | Yes | 6 |
| CA09 | BE18, #3 | De novo deletion | Deleted | PH | Yes | Yes; speech delay | ND | IS | ND | ND | 4 |
| CA09 | BE18, #4 | De novo deletion | Deleted | PH; HPM; MCP; polymicrogyria | Yes | Yes; speech delay | ND | Yes | ND | Yes | 5 |
| AK13 | BE18, #5; RE20, #27 | De novo deletion (582 Kb) | Deleted; (del. includes FLJ42709, FAM172A, POU5F2, and MIR2277) | OA (small OC) | Yes, DMD | No but speech delay | OA; GVI | No | ADHD | Yes | 6 |
| SA13 | BE18, #6; RE20, #53 | De novo MM in LBD | p.Arg404His | ND | ND | ND | ND | ND | ASD | ND | 1 |
| BO14 | LOVD: NR2F1_000001; BO14, #2; BE18, #8; RE20, #13 | De novo MM in DBD | p.Ser113Arg | OA (small OD and OC) | Yes | No or ND | OA; P/SOD; CVI; GVI | ND | ND | Yes | 4 |
| BO14 | LOVD: NR2F1_000002; BO14, #1; BE18, #7; RE20, #14 | De novo MM in DBD | p.Arg115Pro | normal | No | Yes (IQ 48) | OA; P/SOD; small ON; CVI; GVI | ND | ND | ND | 2 |
| BO14 | LOVD: NR2F1_000003; BO14, #3; BE18, #9; RE20, #48 | De novo MM in LBD | p.Leu252Pro | ND | Yes | Yes (IQ 55–65) | P/SOD; CVI; GVI | ND | ND | Yes | 4 |
| BO14 | BO14, #4; BE18, #10; RE20, #28 | Deletion (0.83 Mb) | Deleted; (del. includes FAM172A, KIAA0825) | ND | No | Mild (IQ 61–74) | P/SOD; CVI; GVI | ND | ND | ND | 2 |
| BO14 | BO14, #5; BE18, #11; RE20, #24 | De novo deletion (2.83 Mb) | Deleted; (del. includes FAM172A, KIAA0825, ANKRD31) | Normal or ND | Yes | No (IQ ND) | P/SOD; small ON; CVI; GVI | ND | ND | ND | 2 |
| BO14 | LOVD: NR2F1_000004; BO14, #6; CH16, #12; RE20, #12 | De novo MM in DBD | p.Arg112Lys | Normal or ND | Yes | Yes (IQ 52) | OA; P/SOD; mild GVI | ND | ASD; OCD | ND | 4 |
| HF15; HF17 | LOVD: NR2F1_000018; CH16, #14; RE20, #18 | De novo MM in DBD | p.Arg135Cys | Normal or ND | Yes, DMD | Yes (DQ < 20); speech delay; non-verbal | Bilateral OA | West Syndrome; IS and FS; generalized tonic seizures | ASD traits | ND | 5 |
| DI16 | LOVD: NR2F1_000057; CH16, #15; RE20, #11 | De novo in-frame deletion in DBD | p.Phe110del | CC thinning; LV asymmetry; septum pellucidum agenesis; abnormal gyration | Yes | Severe; non-verbal | No or ND | West Syndrome; spasms at 3 mo; IS; hypsarrythmic EEG; electroclinical spasms | ASD | Global | 6 |
| CH16 | LOVD: NR2F1_000041; CH16, #1; BE18, #16; RE20, #16 | De novo MM in DBD | p.Cys128Arg | CC thinning; WM reduction; leukodystrophy | Yes, DMD | Yes (IQ ND); speech delay; non-verbal | OA; GVI | Epilepsy with staring spells and generalized tonic-clonic seizures | ASD; self-injurious behavior; head-banging | Yes | 7 |
| MI14; CH16 | LOVD: NR2F1_000075; CH16, #2; BE18, #17; RE20, #17 | De novo MM in DBD | p.Arg135Ser | CC thinning; WM reduction; ON malformation and OC bilateral hypoplasia | Yes, DMD | Yes (IQ ND); speech delay | Mild OA; ONH; CVI; GVI | IS; Occipital lobe epilepsy | ASD; head-banging | Profound, axial and appendicular | 7 |
| CH16; EL17 | LOVD: NR2F1_000007; CH16, #3; BE18, #18; RE20, #19 | De novo MM in DBD | p.Cys138Tyr | WM reduction | Global | Yes | OA; GVI | FS; Abnormal EEG during sleep | ASD; RB (persistent head-banging) | No | 6 |
| CH16 | LOVD: NR2F1_000058; CH16, #4; BE18, #19; RE20, #21 | De novo MM in DBD | p.Arg142Leu | CC thinning at 7 mo | Yes, DMD | Yes (IQ ND); speech delay; non-verbal | OA; P/SOD; small ON; CVI; GVI | IS; atonic seizures with markedly abnormal EEG | ND | Yes | 6 |
| CH16 | LOVD: NR2F1_000010; CH16, #5; BE18 #20; RE20 #22 | De novo MM in DBD | p.Cys146Arg | CC thinning and septo-optic dysplasia | Yes, DMD | Yes (IQ ND); speech delay; non-verbal | OA; GVI | No | ASD traits; RB (self-stimulatory behaviors) | Yes | 6 |
| CH16 | LOVD: NR2F1_000024; CH16, #6; BE18, #21; RE20, #47; | De novo MM in DBD | p.Ala155Thr | Normal or ND | No | Mild speech delay (pronunciation; dysarthria) | No or ND | No | NO or ND | Yes | 2 |
| CH16 | LOVD: NR2F1_000078; CH16, #7; BE18, #22; RE20, #51 | De novo MM in LBD | p.Gly368Asp | Normal or ND | Yes | Yes (IQ ND); speech delay | No or ND | First generalized seizure at 18 yo | ASD; RB; aggressive behavior | No | 4 |
| CH16 | LOVD: NR2F1_000057; CH16, #8; BE18, #23; RE20, #10 | De novo in-frame deletion in DBD | p.Phe110del | CC thinning | Yes, DMD | Yes (IQ ND); speech delay; non-verbal | OA; ONH; CVI; GVI | IS | No or ND | Yes | 6 |
| CH16 | LOVD: NR2F1_000053; CH16, #9; CH16, #24; RE20, #40 | De novo frameshift truncation | p.Gly35Argfs*361 | Normal or ND | Yes, DMD | Yes (IQ 55–69; verbal IQ 35–40 at 16 yo); speech delay | OA; P/SOD; CVI; GVI | Few seizures at 3–4 yo | ASD; RB including PDD-NOS at 22 yo; ADHD | Yes | 6 |
| CH16 | LOVD: NR2F1_000055; CH16, #10; BE18, #25; RE20, #41 | De novo frameshift truncation | p.His97Hisfs*22 | ND | Yes | Yes (IQ ND); speech delay | OA; ONH; GVI | No | ASD; OCB/RB; ADHD | Yes | 5 |
| CH16 | LOVD: NR2F1_000052; CH16, #11; BE18, #26; RE20, #36 | De novo TIV | p? | Normal or ND | Yes, DMD | Yes (IQ ND); speech delay; non-verbal | OA; ONH; GVI | No | ASD; RB (head banging) | Yes | 5 |
| CH16 | LOVD: NR2F1_000052; CH16, #12; BE18, #27; #37 in RE20, #37 | De novo TIV | p? | CC thinning; ONH | Yes, DMD | Yes (IQ ND); speech delay; non-verbal | OA; ONH; P/SOD; CVI; GVI | Yes | ASD traits | Yes | 7 |
| CH16 | LOVD: NR2F1_000048; CH16, #13; BE18, #28; RE20, #35 | De novo TIV | p.M1? | ND | Yes, DMD | Yes (FSIQ in the 40 s); speech delay | OA; ONH; CVI; GVI | No | ASD; head banging | Substantial, central | 5 |
| CH16 | LOVD: NR2F1_000048; CH16, #14; BE18, #29; RE20, #38 | De novo TIV | p.M1? | CC and CS thinning; pyramidal decussation agenesis; right vs. left fiber directionality asymmetry | Yes, DMD | Yes (IQ ND); speech delay; non-verbal | OA; coloboma; ONH; GVI | Seizure at 3 yo, complex partial, left parietal | OCB (hand stereotypes); ADHD | Yes | 7 |
| CH16 | LOVD: NR2F1_000042; CH16, #15; BE18, #30; RE20, #39 | De novo TIV | p? | Cerebral malformations; bilateral HPM | Yes, DMD | Yes (IQ ND); speech delay; non-verbal | OA; GVI | Tonic-clonic seizures at 13 and 18 yo | OCB | Yes | 7 |
| CH16 | CH16, #16; BE18, #31; RE20, #29 | De novo deletion (0.2 Mb) | Deleted; (del. includes FAM172A, partial) | ND | Yes, DMD | Yes (IQ ND); speech delay | OA; P/SOD; pigmented maculae; GVI | No | ADHD | Yes | 5 |
| CH16 | CH16, #17; BE18, #32; RE20, #31 | Deletion (0.9 Mb) | Deleted; (del. includes FAM172A; KIAA0825, partial) | ND | Yes | Yes (IQ ND); speech delay | OA; P/SOD; GVI | No | ASD; ADHD | No | 4 |
| CH16 | CH16, #18; BE18, #33; RE20, #32 | Parental (son of CH16, #17), deletion (0.9 Mb) | Deleted | CC agenesis; DM of the EC and IC anterior limb; focal abnormality of the right CB | Yes, DMD | Yes (IQ ND); speech delay | OA; P/SOD; GVI | No | ASD traits; ADHD | Axial | 6 |
| CH16 | CH16, #19; BE18, #34; RE20, #30 | Deletion (1.2 Mb) | Deleted; (del. Includes FAM172A, KIAA0825, ANKRD31) | ND | Yes | Yes (verbal IQ 96; non-verbal IQ 70) | OA; GVI | No | ASD; PDD-NOS | No | 4 |
| CH16 | CH16, #20; BE18, #35; RE20, #23 | Deletion (5.0 Mb) | Deleted; (del. Includes FAM172A, KIAA0825, ANKRD32, MCTP30) | MCP | Yes | Yes (IQ ND) | No or ND | No | ND | Low muscle tone, normal mass and strength | 4 |
| KA17 | LOVD: NR2F1_000039; BE18, #36; RE20, #1 | De novo MM in DBD | p.Cys86Phe | CC thinning; WM reduction; MCP | Yes, DMD | Yes (DQ < 25 at 14 yo); speech delay; non-verbal | OA; mild bilateral ONH; CVI; GVI | One episode of IS; left occipital onset seizure in EEG; FS | Severe ASD; RB (self-stimulating, self-injurious behavior); limited social interaction | Yes | 7 |
| KA17 | LOVD: NR2F1_000079; BE18, #37; RE20, #52 | De novo MM in LBD | p.Leu372Pro | ND | Yes, DMD | Yes (IQ ND); speech delay | OA; GVI | ND | RB; ADHD | Yes | 5 |
| VI17 | LOVD: NR2F1_000017 | MM in DBD | p.Gly105Asp | Cerebral malformations | ND | Yes (IQ ND) | No or ND | ND | ND | ND | 2 |
| MH18 | LOVD: NR2F1_000040; BE18, #38; RE20, #5 | De novo MM in DBD | p.Lys96Glu | CC thinning | Yes | Yes (IQ ca. 30–50); speech delay | Mild OA; CVI; GVI | No | ND | Yes | 5 |
| PA19 | LOVD: NR2F1_000038; RE20, #45; JU21, #10 | Truncation | p.Tyr171* | CC thinning | Yes | Yes; mild (IQ ca. 77–80) | OA; GVI | No | Behavioral disorders; ADHD | ND | 5 |
| BO20 | LOVD: NR2F1_000037; RE20, #43 | De novo truncation | p.Gln28* | ONH | No | No (verbal IQ 141; nonverbal IQ 63) | OA; ONH; CVI; mild GVI | No; EEG showed rare isolated sharp waves from central regions | ASD (hand flapping and toe walking at 24 mo); behavioral disorders; ADHD | Yes | 5 |
| BE20 | LOVD: NR2F1_000059; BE20, #1 | De novo MM in DBD | p.Arg142His | CC thinning; OA (OC and nerve thinning); abnormal gyration | Yes | Yes | OA; amblyopia | IS at 8 mo | ASD and ADHD traits | Yes | 7 |
| BE20 | LOVD: NR2F1_000060; BE20, #2 | De novo truncation | p.Gln244* | CC thinning; ventricular asymmetry and enlargement; abnormal gyration; polymicrogyria | Yes | Yes | No or ND | ND | Behavioral disorders | Yes | 5 |
| BE20 | LOVD: NR2F1_000054; BE20, #3; JU21, #4 | De novo truncation | p.Glu39* | CC and OC thinning; CB malformation; ectopic nodular heterotopy; abnormal gyration | Yes | Yes (speech difficulties) | Severe bilateral OA; LVA | 3–4 ES/y | Stereotypical movements; RB; ADHD | Yes | 7 |
| BE20 | LOVD: NR2F1_000048; BE20, #4 | De novo TIV | p? | CC thinning; cortical malformation; abnormal gyration | Yes | Yes (speech difficulties) | OA | ND | ASD and ADHD traits; behavioral disorders | No | 5 |
| BE20 | LOVD: NR2F1_000056; BE20, #5 | De novo MM in DBD | p.Tyr98His | CC thinning; OC hypoplasia; abnormal gyration | Yes | Yes | OA | ND | ASD traits; behavioral disorders; stereotypical movements | Yes | 6 |
| BE20 | LOVD: NR2F1_000061; BE20, #6 | De novo frameshift truncation | p.Lys323Serfs*73 | Short CC; ON and chiasm thinning; hypoplastic olfactory lobes; abnormal gyration | Yes, DMD | Yes (speech difficulties) | OA; LVA | ND | ASD traits | No | 5 |
| ZO20 | LOVD: NR2F1_000085 | De novo truncation | p.Ser201* | ND | Mild/moderate | Mild/moderate | Bilateral P/SOD; LVA | ND | ND | ND | 2 |
| HO20 | LOVD: NR2F1_000084; RE20, #44 | De novo truncation | p.Glu85* | Normal or ND | Yes | Yes (IQ 69) | OA; GVI | Spells of behavioral arrest and non-responsiveness | ASD; auditory hallucinations and delusions; crying episodes | Yes | 6 |
| WA20 | LOVD: NR2F1_000051 | Frameshift truncation | p.Asn362fs*33 | CC; ON and OC hypoplasia; mild MCP | Apparent at 8 mo | Speech delay | Severe GVI | Myoclonic astatic seizures at 2½ yo | ASD | ND | 6 |
| MI20 | LOVD: NR2F1_000034; MI20, #1 | De novo MM in DBD | p.Gly105Ser | Benign enlargement of the subarachnoid spaces (BESS) | Yes, DMD | Speech delay; non-verbal until 2 yo | Bilateral OA; GVI | Myoclonic epilepsy diagnosed at 3 yo | RB | ND | 6 |
| MI20 | LOVD: NR2F1_000034; MI20, #2 | De novo MM in DBD | p.Gly105Ser | LV enlargement; intraventricular arachnoid cyst | Yes, DMD | Speech delay; non-verbal until 2 yo | Bilateral OA; GVI | Myoclonic epilepsy diagnosed at 4 yo | RB | ND | 6 |
| ST20 | LOVD: NR2F1_000035 | MM in DBD | p.Lys107Glu | CC; ON; OC and optic tracts atrophy; complex pituitary cyst. | Marked and global; DMD | ND | Declining visual acuity; legally blind by 10 yo | 1–3 yo + 30 episodes of FS; occasionally with myoclonus and generalized seizures | Aggressive behavior; depression; hallucinations | Yes | 6 |
| RE20 | LOVD: NR2F1_000065; RE20, #33 | De novo TIV | p.M1? | ND | No | ND | No or ND | No | ND | Yes | 1 |
| RE20 | LOVD: NR2F1_000048; RE20, #34 | De novo TIV | p.M1? | ND | Yes, DMD | Speech delay; non-verbal | OA; small ON; CVI; GVI | FS | ASD | Yes | 5 |
| RE20 | LOVD: NR2F1_000067; RE20, #2 | De novo MM in DBD | p.Cys86Arg | CC thinning | Yes | Speech delay; non-verbal | OA; CVI; GVI | IS | ASD traits | Yes | 7 |
| RE20 | LOVD: NR2F1_000068; RE20, #3; RO20, #170 | De novo MM in DBD | p.Val88Met | Normal or ND | Yes | Speech delay; non-verbal | OA; CVI; GVI | Onset at 9 wo; IS; focal and partial seizures; myoclonic jerks | ASD; RB (head banging) | Yes | 6 |
| RE20 | LOVD: NR2F1_000009; RE20, #4 | MM in DBD | p.Gly95Val | ND | Yes, DMD | Yes (IQ 56); speech delay | P/SOD; small ON; CVI; GVI | IS and absence seizures | ASD traits | Yes | 6 |
| RE20 | LOVD: NR2F1_000069; RE20, #6 | MM in DBD | p.Hys97Pro | Slightly decreased brain volume | Yes | Yes (IQ ND); speech delay; non-verbal | OA; CVI; GVI | Myoclonic seizures | ASD (severe) | Yes | 7 |
| RE20 | LOVD: NR2F1_000070; RE20, #7 | De novo MM in DBD | p.Tyr98Cys | Abnormal | Yes | Speech delay | P/SOD; ONH; CVI; GVI | Myoclonic; absence seizures | ASD; RB (head banging); ADHD | Yes | 7 |
| RE20 | LOVD: NR2F1_000071; RE20, #8 | De novo MM in DBD | p.Glu104Gly | ND | Yes | Speech delay; non-verbal | OA; CVI; GVI | No | ASD traits | Yes | 5 |
| RE20 | LOVD: NR2F1_000072; RE20, #9 | MM in DBD | p.Ser108Ile | ON thinning and small OC | Yes | Yes (IQ ND); speech delay; non-verbal | OA; small ON; CVI; GVI | No | ASD traits | Yes | 6 |
| RE20 | LOVD: NR2F1_000073; RE20, #15 | MM in DBD | p.Cys122Ser | ND | Yes, DMD | Speech delay; non-verbal | OA; GVI | IS | ASD traits | Yes | 5 |
| RE20 | LOVD: NR2F1_000074; RE20, #42 | frameshift truncation | p.Asn127Lysfs*270 | ND | Yes, DMD | Speech delay | ONH; CVI; GVI | Yes | ASD; auditory hallucinations | Yes | 6 |
| RE20 | LOVD: NR2F1_000076; RE20, #20 | De novo MM in DBD | p.Gln139His | CC thinning; DM; ON thinning and small OC | Yes, DMD | Speech delay | OA; CVI; GVI | No | ASD | Yes | 6 |
| RE20 | LOVD: NR2F1_000077; RE20, #49 | MM in LBD | p.Ala311Pro | Normal or ND | Yes | Mild (FSIQ 80 below average); speech delay | P/SOD; mild GVI | Generalized Myoclonic and absence seizures | ASD | Yes | 6 |
| RE20 | De novo MM in LBD | p.Glu318Asp | Abnormal | No but mild DMD | No (IQ 94; performance IQ 54) | OA; CVI; GVI | Atonic; Rolandic epilepsy | ASD | No | 4 | |
| RE20 | LOVD: NR2F1_000021; RE20, #46 | De novo truncation | p.Arg373* | CC; ON and OC thinning | Yes, DMD | Mild (DQ ca. 60–70); speech delay | P/SOD; ONH; CVI; GVI | No | ASD | Yes | 6 |
| RE20 | LOVD: NR2F1_000036; RE20, #54 | De novo MM in LBD | p.Met406Thr | Small ON; Abnormal MRI | Yes, DMD | Yes (IQ ND); speech delay | CVI; GVI | No | ASD | Yes | 6 |
| RE20 | LOVD: NR2F1_000063; RE20, #25 | Maternal, deletion (2.5 Mb) | Deleted; (del. includes FLJ42709, FAM172A, MIR2277, POU5F2, KIAA0825, MIR1974, ANKRD32, MCTP1, FAM81B, TTC37) | ND | Yes | Yes (IQ ND); speech delay | OA; CVI; GVI | Absence and tonic seizures | ASD; PDD-NOS; OCD; pacing and hitting | Yes | 5 |
| RE20 | LOVD: NR2F1_000064; RE20, #26 | Deletion (0.97 Mb) | Deleted | ND | Yes | Speech delay | OA; small ON; CVI; GVI | No | ASD | Mild | 5 |
| JU21 | JU21, #1 | Frameshift truncation | p.Ala2Glnfs*3 | CC thinning; abnormal gyration | Yes; mild | ND | OA; ONH; LVA | Occasional epileptic-like state during light sleep; FS at 4 yo; convulsions at 8 yo | ASD; ADHD | Hypotonia and hyperlaxity | 6 |
| JU21 | JU21, #2 | Frameshift truncation | p.Asn24Glyfs*379 | Normal or ND | Yes | Yes (IQ ND); speech difficulties; learning disability | OA; ONH; CVI; LVA | No | ND | ND | 3 |
| JU21 | JU21, #3 | AA duplication | p.Arg31dup | Normal or ND | Yes | Yes (IQ ND); learning disability | OA; CVI; LVA | No | ND | ND | 3 |
| JU21 | LOVD: NR2F1_000069; JU21, #5 | De novo MM in DBD | p.Hys97Pro | CC; ON and OC thinning; periventricular leukomalacia; MCP | Yes; global (delayed visual maturation) | Yes (IQ ND); learning disability | OA; LVA | One episode of FS | ASD | Moderate/severe | 7 |
| JU21 | JU21, #6 | De novo truncation | p.Leu118* | CC mild foreshortening | Yes; global | Yes (IQ ND); learning disability | OA; LVA | No | ND | Yes | 5 |
| JU21 | JU21, #7 | (Likely) de novo truncation | p.Tyr120* | WM abnormalities | Yes; pervasive; global apraxia | Yes (IQ ND); speech delay; learning disability | OA; LVA | Myoclonic epilepsy; focal impaired awareness seizures | ASD; ADHD | ND | 6 |
| BA19; JU21 | LOVD: NR2F1_000086; JU21, #8 | De novo MM in DBD | p.Cys122Trp | WM reduction; CC thinning | Yes; global | Yes (IQ ND); learning disability | OA; CVI; LVA | IS; Myoclonic epilepsy | ASD; ADHD | Yes | 7 |
| JU21 | JU21, #9 | De novo MM in DBD | p.Ala155Thr | WM reduction; ON thinning | Yes | Yes (IQ ND); speech delay; learning disability | CVI; LVA | No | ASD; anxiety; limited attention span | ND | 5 |
| JU21 | JU21, #11 | De novo MM in LBD | p.Thr200Arg | Lateral and third ventricles enlargement; MCP | Global | Yes (IQ ND); learning disability | Central, steady, maintained | No | ND | Yes | 5 |
| JU21 | JU21, #12 | De novo truncation | p.Trp233* | CC; ON and OC thinning; WM delayed maturation; brain abnormalities | Yes | Yes (IQ ND); speech difficulties | OA; microphthalmia; small ON head; CVI | No | Limited concentration and short attention span | ND | 5 |
| JU21 | LOVD: NR2F1_000082; JU21, #13 | De novo MM in LBD | p.Glu342Lys | Normal CC e ON; OC atrophy and defective rotation; Normal gyration | No | No | OA; ONH; LVA | No | ND | ND | 2 |
| JU21 | JU21, #14 | (Likely) de novo deletion in LBD | p.Glu346_Gln349del | ND | Yes; walking delay | Yes (IQ ND); speech delay; dyslexia; learning disability | ONH; CVI; LVA | No | ND | ND | 3 |
| JU21 | LOVD: NR2F1_000079; JU21, #15 | Familial MM in LBD | p.Leu372Pro | ND | Yes; walking delay | Yes (IQ ND); speech delay | Small ON head; CVI; LVA | No | ND | ND | 3 |
| JU21 | LOVD: NR2F1_000079; JU21, #16 | Familial MM in LBD | p.Leu372Pro | Normal or ND | Yes; walking delay | Yes (IQ ND); speech delay; | OA; ONH; CVI; LVA | One episode of FS | ND | ND | 4 |
| JU21 | LOVD: NR2F1_000079; JU21, #17 | Familial MM in LBD | p.Leu372Pro | Normal or ND | Yes; walking delay | Yes (IQ ND); speech delay; | OA; CVI; LVA | No | ND | ND | 3 |
| JU21 | JU21, #18 | Familial deletion in LBD | p.Arg373_Leu374del | ND | No | ND | OA; ONH; LVA | No | ND | ND | 1 |
| JU21 | JU21, #19 | Familial deletion in LBD | p.Arg373_Leu374del | ON atrophy | No | ND | OA; ONH; LVA | No | ND | ND | 2 |
| JU21 | JU21, #20 | De novo MM in LBD | p.Gly395Ser | ON atrophy; WM loss | Yes | Yes (IQ ND); learning disability | CVI; LVA | No | ND | Generalized | 5 |
| JU21 | LOVD: NR2F1_000083; JU21, #21 | De novo truncation | p.Glu400* | CC thinning; ON and OC atrophy; abnormal gyration | Yes | Yes (IQ ND); learning disability | OA; ONH; LVA | No | ASD; behavioral disorders | ND | 5 |
| JU21 | JU21, #22 | De novo whole-gene deletion (599 Kb) | deleted; (del. includes FAM172A; NR2F1-AS1, partial; KIAA0825, last exon) | CC thickening; ON atrophy; cerebral vascular system abnormalities | Yes | Yes (IQ ND); mild speech delay; learning disability | OA; LVA | No | ND | ND | 4 |
| JS20 | LOVD: NR2F1_000036 | De novo MM in LBD | p.Met406Thr | DM | Yes | Severe (IQ ND); speech delay; non-verbal | OA; suspected ON dysplasia; GVI | Seizures from 4 mo | Short attention span | ND | 6 |
| GA21 | LOVD: NR2F1_000048 | De novo TIV | p.M1? | Brain abnormalities; ON; OC and optic tract hypoplasia | Yes | Severe (IQ ND) | Right iris and chorioretinal coloboma; small ON; bilateral P/SOD; LVA | EEG at 12 yo showed possible occipital seizures | ND | Yes | 6 |