Table 1.

Brain disorders in which axon guidance alterations have been described or inferred.

Disorder	Human Gene	Axon Guidance-Related Defect	Symptoms	Reference
Congenital mirror movements (CMM) and partial or complete agenesis of the corpus callosum	NETRIN1 (NTN1)	Corticospinal tract (CST) abnormality	Involuntary movements of one hand that mirror intentional movements of the opposite hand	[77,78]
Congenital mirror movements (CMM) and/or isolated agenesis of the corpus callosum	Deleted in colorectal cancer (DCC)	Decreased crossing of descending corticospinal tract projections	Variable range of intellectual disabilities, cognitive impairment, language delay, and visual and spatial deficits	[79,80]
Developmental split-brain syndrome (gaze palsy, familial horizontal, with progressive scoliosis 2, with impaired intellectual development)	Deleted in colorectal cancer (DCC)	Agenesis of the corpus callosum and absence of the anterior and hippocampal commissures	Neurological abnormalities, horizontal gaze palsy, intellectual disability, and progressive scoliosis	[81]
Horizontal gaze palsy with progressive scoliosis (HGPPS)	Roundabout guidance receptor 3 (ROBO3)	Abnormal flattening of the basis pontis and hypoplasia in the pontine tegmentum; anomalous innervations of the lateral rectus muscle of the eye by the abducens supranuclear nerve	Horizontal gaze palsy, intellectual disability and progressive scoliosis	[82,83,84,85]
CRASH syndrome (Corpus callosum agenesis, Retardation, Adducted thumbs, Shuffling gait, and Hydrocephalus)	L1CAM	Agenesis of the corpus callosum and corticospinal tract	Microcephaly, mental retardation, spastic paraparesis	[86,87]
Kallman syndrome (X-linked)	ANOS1 (KAL1)	Defective olfactory axon guidance and migration	Congenital anosmia, hypogonadotropic hypogonadism, mirror movements, and aberrant corticospinal tract	[89,90]
Joubert syndrome and related disorders (JSRD)	Multiple genes (AHI1, NPHP1, CEP290, TMEM67, RPGRIP1, ARL13B, CC2D2A)	Hypotonia, ataxia, mental retardation, altered respiratory patterns, social disabilities, and synkinetic mirror movements	Cerebellar vermian hypoplasia, reduction in pontine neurons, and reduced decussation of the superior cerebellar peduncles.	[92,93]
Duane retraction syndrome (DRS)	α2-CHIMERIN	Absence of abducens motor neurons and nerves; aberrant innervation of the lateral rectus muscle by the oculomotor nerve	Restricted horizontal gaze and ocular synkinesis	[95,96]
Cortical dysplasia, complex, with other brain malformations 1 (CDCBM1)	Beta tubulin protein family member TUBB3	Thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis	Severe mental retardation, strabismus, axial hypotonia, and spasticity	[99]
Congenital fibrosis of the extraocular muscles 3 (CFEOM3)	Beta tubulin protein family member TUBB3	Dysgenesis of the corpus callosum and anterior commissure (AC), and internal capsule; generalized loss of white matter; basal ganglia dysmorphisms	Aberrant eye movements, facial weakness, axonal peripheral neuropathy, contractures of the wrist and fingers, delayed development, and learning disabilities	[100]
Craniofrontonasal syndrome (CFNS)	Ephrin B1(EFNB1)	Dysgenesis or agenesis of the corpus callosum	Variable difficulties in speech and language, limited or no intellectual disabilities, facial asymmetry, skeletal and dermatological abnormalities	[101]
Mucopolysaccharidosis type II (Hunter syndrome)	Iduronate sulfatase (IDS)	Indirect experimental observation	Mental retardation, language delay, cognitive impairment	[103]
Mucopolysaccharidosis type IIIb (Sanfilippo Syndrome)	α-N-acetylglucosaminidase (NAGLU)	Indirect experimental observation	Mental retardation, cognitive decline, dysphagia, sleep problems, seizures	[102]
Mucopolysaccharidosis type VII (Sly syndrome)	β-glucuronidase (GUSB)	Indirect experimental observation	developmental Delay, speech delay, intellectual disability of variable degree	[104]