Duane-radial ray syndrome

Summary

Duane-radial ray syndrome (MONDO:0011812) is a disease caused by SALL4 (GenCC Definitive), with 3 cohort genes and 1 clinical trial.

At a glance

• Causal gene: SALL4 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 414
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Duane-radial ray syndrome
Mondo ID	MONDO:0011812
OMIM	607323
Orphanet	93293, 959
DOID	DOID:0060747
SNOMED CT	699867001, 720415006
UMLS	C1623209
MedGen	301647
GARD	0009182
Is cancer (heuristic)	no

Also known as: acro-renal-ocular syndrome · DR syndrome · DRRS · Duane anomaly with radial abnormalities and deafness · Duane anomaly with radial ray abnormalities and deafness · Duane-radial ray syndrome · Okihiro syndrome

Data availability: 414 ClinVar variants · 4 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › Duane-radial ray syndrome

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (2): Okihiro syndrome due to 20q13 microdeletion, Okihiro syndrome due to a point mutation

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

414 retrieved; paginated sample, class counts are floors:

207 uncertain significance, 84 likely benign, 38 pathogenic, 36 conflicting classifications of pathogenicity, 19 benign, 17 benign/likely benign, 9 likely pathogenic, 2 not provided, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3327	NC_000020.11:g.(51758515_51770114)(51894383?)del	ATP9A	Pathogenic	no assertion criteria provided
3390931	NM_006390.4(IPO8):c.2600_2601delinsAA (p.Phe867Ter)	IPO8	Pathogenic	criteria provided, single submitter
1362243	NC_000020.10:g.(?50400804)(50418947_?)del	SALL4	Pathogenic	criteria provided, single submitter
1411759	NM_020436.5(SALL4):c.1959dup (p.Pro654fs)	SALL4	Pathogenic	criteria provided, single submitter
1415336	NM_020436.5(SALL4):c.1657C>T (p.Gln553Ter)	SALL4	Pathogenic	criteria provided, single submitter
1455097	NM_020436.5(SALL4):c.1717C>T (p.Arg573Ter)	SALL4	Pathogenic	criteria provided, multiple submitters, no conflicts
1684297	NM_020436.5(SALL4):c.1068del (p.Lys357fs)	SALL4	Pathogenic	criteria provided, single submitter
1697971	NM_020436.5(SALL4):c.712C>T (p.Gln238Ter)	SALL4	Pathogenic	criteria provided, single submitter
1806356	NM_020436.5(SALL4):c.2252del (p.Asn751fs)	SALL4	Pathogenic	criteria provided, single submitter
2015460	NM_020436.5(SALL4):c.2280dup (p.Asn761fs)	SALL4	Pathogenic	criteria provided, single submitter
2035463	NM_020436.5(SALL4):c.1472C>A (p.Ser491Ter)	SALL4	Pathogenic	criteria provided, single submitter
2087818	NM_020436.5(SALL4):c.474_475del (p.Glu158fs)	SALL4	Pathogenic	criteria provided, single submitter
218947	NM_020436.5(SALL4):c.410dup (p.Gly138fs)	SALL4	Pathogenic	no assertion criteria provided
2412780	NM_020436.5(SALL4):c.1625del (p.Pro542fs)	SALL4	Pathogenic	criteria provided, single submitter
2502302	NM_020436.5(SALL4):c.2456dup (p.Met819fs)	SALL4	Pathogenic	criteria provided, single submitter
2633659	NM_020436.5(SALL4):c.1242_1245del (p.Cys415fs)	SALL4	Pathogenic	criteria provided, multiple submitters, no conflicts
2728404	NM_020436.5(SALL4):c.1994_1995del (p.Phe665fs)	SALL4	Pathogenic	criteria provided, single submitter
2756162	NM_020436.5(SALL4):c.2424dup (p.Ala809fs)	SALL4	Pathogenic	criteria provided, single submitter
3318	NM_020436.5(SALL4):c.1954C>T (p.Gln652Ter)	SALL4	Pathogenic	no assertion criteria provided
3319	NM_020436.5(SALL4):c.1054del (p.Ala352fs)	SALL4	Pathogenic	no assertion criteria provided
3320	NM_020436.5(SALL4):c.941dup (p.Leu315fs)	SALL4	Pathogenic	no assertion criteria provided
3321	NM_020436.5(SALL4):c.1904del (p.Phe635fs)	SALL4	Pathogenic	no assertion criteria provided
3322	NM_020436.5(SALL4):c.2593C>T (p.Arg865Ter)	SALL4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3323	NM_020436.5(SALL4):c.2425del (p.Ala809fs)	SALL4	Pathogenic	no assertion criteria provided
3324	NM_020436.5(SALL4):c.326del (p.Pro109fs)	SALL4	Pathogenic	no assertion criteria provided
3325	NM_020436.5(SALL4):c.523A>T (p.Lys175Ter)	SALL4	Pathogenic	no assertion criteria provided
3326	NM_020436.5(SALL4):c.1849C>T (p.Arg617Ter)	SALL4	Pathogenic	criteria provided, single submitter
3329	NM_020436.5(SALL4):c.2663A>G (p.His888Arg)	SALL4	Pathogenic	no assertion criteria provided
3362635	NM_020436.5(SALL4):c.1557del (p.Thr520fs)	SALL4	Pathogenic	criteria provided, single submitter
3639620	NM_020436.5(SALL4):c.1291C>T (p.Arg431Ter)	SALL4	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SALL4	Definitive	Autosomal dominant	Duane-radial ray syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SALL4	Orphanet:2307	IVIC syndrome
SALL4	Orphanet:233	Duane retraction syndrome
SALL4	Orphanet:261638	Okihiro syndrome due to 20q13 microdeletion
SALL4	Orphanet:261647	Okihiro syndrome due to a point mutation
SALL4	Orphanet:959	Acro-renal-ocular syndrome
ATP9A	Orphanet:528084	Non-specific syndromic intellectual disability
IPO8	Orphanet:60030	Loeys-Dietz syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SALL4	HGNC:15924	ENSG00000101115	Q9UJQ4	Sal-like protein 4	gencc,clinvar
ATP9A	HGNC:13540	ENSG00000054793	O75110	Probable phospholipid-transporting ATPase IIA	clinvar
IPO8	HGNC:9853	ENSG00000133704	O15397	Importin-8	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SALL4	Sal-like protein 4	Transcription factor with a key role in the maintenance and self-renewal of embryonic and hematopoietic stem cells.
ATP9A	Probable phospholipid-transporting ATPase IIA	Plays a role in regulating membrane trafficking of cargo proteins, namely endosome to plasma membrane recycling, probably acting through RAB5 and RAB11 activation.
IPO8	Importin-8	Involved in nuclear protein import, either by acting as autonomous nuclear transport receptor or as an adapter-like protein in association with the importin-beta subunit KPNB1.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	2	5.5×	0.081
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SALL4	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Sal_C2H2-zinc-finger
ATP9A	Transcription factor	no	7.6.2.1	P_typ_ATPase, P-type_ATPase_IV, ATPase_P-typ_transduc_dom_A_sf
IPO8	Other/Unknown	no		Importin-beta_N, ARM-like, XPO2_central

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	2
secondary oocyte	2
male germ line stem cell (sensu Vertebrata) in testis	1
Brodmann (1909) area 23	1
Brodmann (1909) area 46	1
middle temporal gyrus	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SALL4	150	broad	marker	secondary oocyte, oocyte, male germ line stem cell (sensu Vertebrata) in testis
ATP9A	299	ubiquitous	marker	middle temporal gyrus, Brodmann (1909) area 46, Brodmann (1909) area 23
IPO8	272	ubiquitous	marker	secondary oocyte, oocyte, tendon of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IPO8	3,145
SALL4	2,243
ATP9A	930

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SALL4	Q9UJQ4	13
ATP9A	O75110	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IPO8	O15397	87.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation	1	292.8×	0.039	SALL4
Transcriptional regulation of pluripotent stem cells	1	181.3×	0.039	SALL4
Gene Silencing by RNA	1	119.0×	0.039	IPO8
PTEN Regulation	1	76.1×	0.039	SALL4
Ion transport by P-type ATPases	1	69.2×	0.039	ATP9A
Regulation of PTEN gene transcription	1	59.5×	0.039	SALL4
Transcriptional regulation by small RNAs	1	48.2×	0.041	IPO8
Ion channel transport	1	32.0×	0.051	ATP9A
Intracellular signaling by second messengers	1	30.4×	0.051	SALL4
PIP3 activates AKT signaling	1	22.3×	0.062	SALL4
Transport of small molecules	1	8.4×	0.146	ATP9A
Gene expression (Transcription)	1	6.0×	0.185	IPO8
Developmental Biology	1	4.8×	0.208	SALL4
Signal Transduction	1	3.4×	0.267	SALL4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of exosomal secretion	1	1404.3×	0.006	ATP9A
regulation of retrograde transport, endosome to Golgi	1	1404.3×	0.006	ATP9A
regulation of endocytic recycling	1	561.7×	0.010	ATP9A
inner cell mass cell proliferation	1	330.4×	0.013	SALL4
phospholipid translocation	1	208.1×	0.016	ATP9A
ventricular septum development	1	165.2×	0.017	SALL4
embryonic limb morphogenesis	1	133.8×	0.018	SALL4
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	1	112.3×	0.019	ATP9A
neuron projection morphogenesis	1	92.1×	0.020	ATP9A
somatic stem cell population maintenance	1	82.6×	0.020	SALL4
neural tube closure	1	62.4×	0.025	SALL4
protein import into nucleus	1	48.0×	0.029	IPO8
endocytosis	1	31.7×	0.041	ATP9A
negative regulation of transcription by RNA polymerase II	1	5.9×	0.194	SALL4
signal transduction	1	5.3×	0.199	IPO8
positive regulation of transcription by RNA polymerase II	1	5.0×	0.200	SALL4
regulation of transcription by RNA polymerase II	1	3.9×	0.236	SALL4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SALL4	0	0
ATP9A	0	0
IPO8	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SALL4	12	Binding:12
IPO8	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATP9A	7.6.2.1	P-type phospholipid transporter

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	SALL4, ATP9A, IPO8

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SALL4	12	—
ATP9A	0	—
IPO8	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03059420	Not specified	RECRUITING	Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies