Males show more serious symptoms than females affected by this disorder.

The symptoms for males are:

1. Profound sensorineural hearing loss i.e, a complete or almost complete loss of hearing caused by abnormalities in the inner ear.

2. Weak muscle tone - Hypotonia.

3. Impaired muscle coordination - Ataxia.

4. Developmental delay.

5. Intellecual disability.

6. Vision loss caused by optic nerve atrophy in early childhood.

7. Peripheral neuropathy.

8. Recurrent infections, especially in the respiratory system.

9. Muscle weakness caused by recurrent infections.

Symptoms for females:

Very rarely seen hearing loss that begins in adulthood (age > 20 years) combined with ataxia and neuropathy. Optic atrophy and retinitis pigmentosa observed in some cases too.

Clinically, three distinct patterns of palmoplantar keratoderma may be identified: diffuse, focal, and punctate.

Laminopathies and other nuclear envelopathies have a large variety of clinical symptoms including skeletal and/or cardiac muscular dystrophy, lipodystrophy and diabetes, dysplasia, dermo- or neuropathy, leukodystrophy, and progeria (premature aging). Most of these symptoms develop after birth, typically during childhood or adolescence. Some laminopathies however may lead to an early death, and mutations of lamin B (LMNB1 gene) may be lethal before or at birth.

Symptoms of the Roussy–Lévy syndrome mainly stem from nerve damage and the resulting progressive muscle atrophy. Neurological damage may result in absent tendon reflexes (areflexia), some distal sensory loss and decreased excitability of muscles to galvanic and faradic stimulation. Progressive muscle wasting results in weakness of distal limb muscles (especially the peronei), gait ataxia, pes cavus, postural tremors and static tremor of the upper limbs, kyphoscoliosis, and foot deformity.

These symptoms frequently translate into delayed onset of ability to walk, loss of coordination and balance, foot drop, and foot-bone deformities. They are usually first observed during infancy or early childhood, and slowly progress until about age 30, at which point progression may stop in some individuals, or symptoms may continue to slowly progress.

Onset occurs in infancy or early childhood, usually before 3 years of age. Progression is slow until the teenage years at which point it may accelerate, resulting in severe disability.

Symptoms are usually more severe and rapidly progressive than in the other more common Charcot–Marie–Tooth diseases. Some patients may never walk and solely use wheelchairs by the end of their first decade, while others may need only a cane (walking stick) or similar support through life.

Dejerine–Sottas disease is characterized by moderate to severe lower and upper extremity weakness and loss of sensation, which occur mainly in the lower legs, forearms, feet and hands. Loss of muscle mass and reduced muscle tone can occur as the disease progresses. Other symptoms may include pain in the extremities, curvature of the spine, clawed hands, foot deformities, ataxia, peripheral areflexia, and slow acquisition of motor skills in childhood. Symptoms that are less common can include limitation of eye movements, other eye problems such as nystagmus or anisocoria, or mild hearing loss.

Some specific symptoms vary from one type of leukodystrophy to the next but the vast majority of symptoms are shared as the causes for the disease generally have the same effects. Symptoms are dependent on the age of onset, which is predominantly in infancy and early childhood, although the exact time of onset may be difficult to determine. Hyperirritability and hypersensitivity to the environment are common, as well as some tell-tale physical signs including muscle rigidity and a backwards-bent head. Botox therapy is often used to treat patients with spasticity. Juvenile and adult onsets display similar symptoms including a decrease or loss in hearing and vision. While children do experience optic and auditory degeneration, the course of the disease is usually too rapid, causing death relatively quickly, whereas adults may live with these conditions for many years. In children, spastic activity often precedes progressive ataxia and rapid cognitive deterioration which has been described as mental retardation. Epilepsy is commonplace for patients of all ages. More progressed patients show weakness in deglutition, leading to spastic coughing fits due to inhaled saliva. Classic symptomatic progression of juvenile x-linked adrenoleukodystrophy is shown in the 1992 film, "Lorenzo's Oil".

Course and timetable are dependent on the age of onset with infants showing a lifespan of 2–8 years, juveniles 2–10 years and adults typically 10+ years. Adults typically see an extended period of stability followed by a decline to a vegetative state and death. While treatments do exist, most are in the experimental phase and can only promise a halt in the progression of symptoms, although some gene therapies have shown some symptomatic improvement. The debilitating course of the disease has led to numerous philosophical and ethical arguments over experimental clinical trials, patients’ rights and physician-assisted suicide.

In an individual with dHMN V, electromyography will show pure motor neuropathy, patterns of weakness without upper motor neuron damage, in the hands. Tendon reflexes will also appear normal. Clinical, electrophysiological, and pathological testing will show a lack of damage to sensory neurons, differentiating this disease from CMT.

Gordon syndrome is an extremely rare disorder that belongs to a group of genetic disorders known as the distal arthrogryposes. These disorders typically involve stiffness and impaired mobility of certain joints of the lower arms and legs (distal extremities) including the knees, elbows, wrists, and/or ankles. These joints tend to be permanently fixed in a bent or flexed position (contractures). Gordon syndrome is characterized by the permanent fixation of several fingers in a flexed position (camptodactyly), abnormal bending inward of the foot (clubfoot or talipes), and, less frequently, incomplete closure of the roof of the mouth (cleft palate). In some cases, additional abnormalities may also be present. The range and severity of symptoms may vary from case to case. Gordon syndrome is inherited as an autosomal dominant trait.

People with ODD syndrome often have a characteristic appearance. Visible features of the condition include:

- small teeth that are prone to caries because of underdeveloped tooth enamel;

- a long, thin nose;

- unusually small eyes; and

- type III syndactyly of the fourth and fifth fingers.

Iris atrophy and glaucoma are more common than average. The size of the eyes often interferes with learning to read; special eyeglasses may be required. Hair may be fine, thin, dry, or fragile; in some families, it is curly.

Neurologic abnormalities may be seen in adults. The neurologic changes may appear earlier in each subsequent generation and can include abnormal white matter, conductive deafness, and various kinds of paresis, including ataxia, spastic paraplegia, difficulty controlling the eyes, and bladder and bowel disturbances.

Diffuse palmoplantar keratoderma is a type of palmoplantar keratoderma that is characterized by an even, thick, symmetric hyperkeratosis over the whole of the palm and sole, usually evident at birth or in the first few months of life. Restated, diffuse palmoplantar keratoderma is an autosomal dominant disorder in which hyperkeratosis is confined to the palms and soles. The two major types can have a similar clinical appearance:

- "Diffuse epidermolytic palmoplantar keratoderma" (also known as "Palmoplantar keratoderma cum degeneratione granulosa Vörner," "Vörner's epidermolytic palmoplantar keratoderma", and "Vörner keratoderma") is one of the most common patterns of palmoplantar keratoderma, an autosomal dominant condition that presents within the first few months of life, characterized by a well-demarcated, symmetric thickening of palms and soles, often with a "dirty" snakeskin appearance due to underlying epidermolysis.

- "Diffuse nonepidermolytic palmoplantar keratoderma" (also known as "Diffuse orthohyperkeratotic keratoderma," "Hereditary palmoplantar keratoderma," "Keratosis extremitatum progrediens," "Keratosis palmoplantaris diffusa circumscripta," "Tylosis," "Unna–Thost disease", and "Unna–Thost keratoderma") is inherited as an autosomal dominant condition and is present from infancy, characterized by a well-demarcated, symmetric, often "waxy" keratoderma involving the whole of the palms and soles.

Onset usually occurs within the first two decades of life, commonly in the teenage years or the twenties. Life expectancy is normal. High arch of the foot (pes cavus) is common. Patients also have trouble controlling their hands, due to muscle loss on the thumb side of the index finger and palm below the thumb. It is rare for a person with this disorder to lose the ability to walk, though changes in gait may occur later in life.

Frequency of this disorder is unknown.

Gordon syndrome (GS), or distal arthrogryposis type 3, is a rare, autosomal dominant disorder characterized by cleft palate and congenital contractures of the hands and feet.

Theoretically, a mutation in any of the may cause disease, but below are some notable ones, with short description of symptoms:

- Adrenoleukodystrophy; leads to progressive brain damage, failure of the adrenal glands and eventually death.

- Alport syndrome; glomerulonephritis, endstage kidney disease, and hearing loss.

- Androgen insensitivity syndrome; variable degrees of undervirilization and/or infertility in XY persons of either gender

- Barth syndrome; metabolism distortion, delayed motor skills, stamina deficiency, hypotonia, chronic fatigue, delayed growth, cardiomyopathy, and compromised immune system.

- Blue cone monochromacy; low vision acuity, color blindness, photophobia, infantile nystagmus.

- Centronuclear myopathy; where cell nuclei are abnormally located in skeletal muscle cells. In CNM the nuclei are located at a position in the center of the cell, instead of their normal location at the periphery.

- Charcot–Marie–Tooth disease (CMTX2-3); disorder of nerves (neuropathy) that is characterized by loss of muscle tissue and touch sensation, predominantly in the feet and legs but also in the hands and arms in the advanced stages of disease.

- Coffin–Lowry syndrome; severe mental retardation sometimes associated with abnormalities of growth, cardiac abnormalities, kyphoscoliosis as well as auditory and visual abnormalities.

- Fabry disease; A lysosomal storage disease causing anhidrosis, fatigue, angiokeratomas, burning extremity pain and ocular involvement.

- Hunter's Syndrome; potentially causing hearing loss, thickening of the heart valves leading to a decline in cardiac function, obstructive airway disease, sleep apnea, and enlargement of the liver and spleen.

- Hypohidrotic ectodermal dysplasia, presenting with hypohidrosis, hypotrichosis, hypodontia

- Kabuki syndrome; multiple congenital anomalies and mental retardation.

- Spinal and bulbar muscular atrophy; muscle cramps and progressive weakness

- Lesch-Nyhan syndrome; neurologic dysfunction, cognitive and behavioral disturbances including self-mutilation, and uric acid overproduction (hyperuricemia)

- Lowe Syndrome; hydrophthalmia, cataracts, intellectual disabilities, aminoaciduria, reduced renal ammonia production and vitamin D-resistant rickets

- Menkes disease; sparse and coarse hair, growth failure, and deterioration of the nervous system

- Nasodigitoacoustic syndrome; mishaped nose, brachydactyly of the distal phalanges, sensorineural deafness

- Nonsyndromic deafness; hearing loss

- Norrie disease; cataracts, leukocoria along with other developmental issues in the eye

- Occipital horn syndrome; deformations in the skeleton

- Ocular albinism; lack of pigmentation in the eye

- Ornithine transcarbamylase deficiency; developmental delay and mental retardation. Progressive liver damage, skin lesions, and brittle hair may also be seen

- Siderius X-linked mental retardation syndrome; cleft lip and palate with mental retardation and facial dysmorphism, caused by mutations in the histone demethylase PHF8

- Simpson-Golabi-Behmel syndrome; coarse faces with protruding jaw and tongue, widened nasal bridge, and upturned nasal tip

- Spinal muscular atrophy caused by UBE1 gene mutation; weakness due to loss of the motor neurons of the spinal cord and brainstem

- Wiskott-Aldrich syndrome; eczema, thrombocytopenia, immune deficiency, and bloody diarrhea

- X-linked Severe Combined Immunodeficiency (SCID); infections, usually causing death in the first years of life

- X-linked sideroblastic anemia; skin paleness, fatigue, dizziness and enlarged spleen and liver.

Roussy–Lévy syndrome, also known as Roussy–Lévy hereditary areflexic dystasia, is a rare genetic disorder of humans that results in progressive muscle wasting. It is caused by mutations in the genes that code for proteins necessary for the functioning of the myelin sheath of the neurons, affecting the conductance of nerve signals and resulting in loss of muscles' ability to move.

The condition affects people from infants through adults and is inherited in an autosomal dominant manner. Currently, no cure is known for the disorder.

Hajdu–Cheney syndrome causes many issues with an individual’s connective tissues. Some general characteristics of an individual with Hajdu–Cheney syndrome include bone flexibility and deformities, short stature, delayed acquisition of speech and motor skills, dolichocephalic skull, Wormian bone, small maxilla, hypoplastic frontal sinuses, basilar impression, joint laxity, bulbous finger tips, and severe osteoporosis. Wormian bone occurs when extra bones appear between cranial sutures. Fetuses with Hajdu–Cheney syndrome often will not be seen to unclench their hands on obstetrical ultrasound. They may also have low-set ears and their eyes may be farther apart than on a usual child, called hypertelorism. Children's heads can have some deformities in their shape and size (plagiocephaly). Early tooth loss and bone deformities, such as serpentine tibiae and fibulae, are also common in those affected.

Laminopathies ("" + "") are a group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear lamina. They are included in the more generic term "nuclear envelopathies" that was coined in 2000 for diseases associated with defects of the nuclear envelope. Since the first reports of laminopathies in the late 1990s, increased research efforts have started to uncover the vital role of nuclear envelope proteins in cell and tissue integrity in animals.

Worth syndrome, also known as benign form of Worth hyperostosis corticalis generalisata with torus platinus, autosomal dominant osteosclerosis, autosomal dominant endosteal hyperostosis or Worth disease, is a rare autosomal dominant congenital disorder that is caused by a mutation in the LRP5 gene. It is characterized by increased bone density and benign bony structures on the palate.

Symptoms of CMT usually begin in early childhood or early adulthood, but can begin later. Some people do not experience symptoms until their early thirties or forties. Usually, the initial symptom is foot drop early in the course of the disease. This can also cause hammer toe, where the toes are always curled. Wasting of muscle tissue of the lower parts of the legs may give rise to a "stork leg" or "inverted champagne bottle" appearance. Weakness in the hands and forearms occurs in many people as the disease progresses.

Loss of touch sensation in the feet, ankles and legs, as well as in the hands, wrists and arms occur with various types of the disease. Early and late onset forms occur with 'on and off' painful spasmodic muscular contractions that can be disabling when the disease activates. High-arched feet (pes cavus) or flat-arched feet (pes planus) are classically associated with the disorder. Sensory and proprioceptive nerves in the hands and feet are often damaged, while unmyelinated pain nerves are left intact. Overuse of an affected hand or limb can activate symptoms including numbness, spasm, and painful cramping.

Symptoms and progression of the disease can vary. Involuntary grinding of teeth as well as squinting are prevalent and often go unnoticed by the person affected. Breathing can be affected in some; so can hearing, vision, as well as the neck and shoulder muscles. Scoliosis is common, causing hunching and loss of height. Hip sockets can be malformed. Gastrointestinal problems can be part of CMT, as can difficulty chewing, swallowing, and speaking (due to atrophy of vocal cords). A tremor can develop as muscles waste. Pregnancy has been known to exacerbate CMT, as well as severe emotional stress. Patients with CMT must avoid periods of prolonged immobility such as when recovering from a secondary injury as prolonged periods of limited mobility can drastically accelerate symptoms of CMT.

Pain due to postural changes, skeletal deformations, muscle fatigue and cramping is fairly common in people with CMT. It can be mitigated or treated by physical therapies, surgeries, and corrective or assistive devices. Analgesic medications may also be needed if other therapies do not provide relief from pain. Neuropathic pain is often a symptom of CMT, though, like other symptoms of CMT, its presence and severity varies from case to case. For some people, pain can be significant to severe and interfere with daily life activities. However, pain is not experienced by all people with CMT. When neuropathic pain is present as a symptom of CMT, it is comparable to that seen in other peripheral neuropathies, as well as postherpetic neuralgia and complex regional pain syndrome, among other diseases.

Individuals affected by an ED syndrome frequently have abnormalities of the hair follicles. Scalp and body hair may be thin, sparse, and very light in color, even though beard growth in affected males may be normal. The hair may grow very slowly or sporadically and it may be excessively fragile, curly, or even twisted.

Fingernails and toenails may be thick, abnormally shaped, discolored, ridged, slow-growing, or brittle. The cuticles may be prone to infections.

Acro–dermato–ungual–lacrimal–tooth (ADULT) syndrome is a rare genetic disease. ADULT syndrome is an autosomal dominant form of ectodermal dysplasia, a group of disorders that affects the hair, teeth, nails, sweat glands, and extremities. The syndrome arises from a mutation in the TP63 gene. This disease was previously thought to be a form of ectrodactyly–ectodermal dysplasia–cleft syndrome (EEC), but was classified as a different disease in 1993 by Propping and Zerres.

Specific types of leukodystrophies include the following with their respective ICD-10 codes when available:

- (E71.3) Adrenomyeloneuropathy

- (E75.2) Alexander disease

- (E75.5) Cerebrotendineous xanthomatosis

- Hereditary CNS demyelinating disease

- (E75.2) Krabbe disease

- (E75.2) Metachromatic leukodystrophy

- (E75.2) Pelizaeus–Merzbacher disease

- (E75.2) Canavan disease

- (G93.49) Leukoencephalopathy with vanishing white matter

- (E71.3) Adrenoleukodystrophy

- (G60.1) Refsum disease

Arts syndrome is a rare metabolic disorder that causes serious neurological problems in males due to a malfunction of the PRPP synthetase 1 enzyme. Arts Syndrome is part of a spectrum of PRPS-1 related disorders with reduced activity of the enzyme that includes Charcot–Marie–Tooth disease and X-linked non-syndromic sensorineural deafness.

ADULT syndrome features include ectrodactyly, syndactyly, excessive freckling, lacrimal duct anomalies, dysplastic nails, hypodontia, hypoplastic breasts and nipples, hypotrichosis, hypohidrosis, broad nasal bridge, midfacial hypoplasia, exfoliative dermatitis, and xerosis. The lack of facial clefting and ankyloblepharon are important because they exist in ectrodactyly–ectodermal dysplasia–cleft syndrome (EEC) but not in ADULT syndrome.

Symptoms of otodental syndrome can and usually appear in early development and progress with age. Although the specific frequency of the symptoms is not known, the duration is recognized to be for life; assuming no treatment has been undergone. The symptoms are variable to each individual, can range greatly in severity and are dependent on gene expression.

More severe symptoms include:

- Globodontia – an abnormal condition that can occur in both primary and secondary tooth development, in which the molars and canines are greatly enlarged. It refers to the enlarged bulbous fused malformed posterior teeth with almost no discernible cusps or grooves. The molars are known to have a rounded globe-like shape. Can attribute to pain.

- Sensorineural hearing loss (SNHL) – also known as nerve related hearing loss, is a form of hearing loss associated with complications within the inner ear.

- Taurodontism – known as a condition in which the body of a tooth is enlarged at the expense of the roots. This results in an enlarged pulp chamber, lack of proper bonding at the cementoenamel junction, and can cause the pulpal floor to be displaced towards the root. Discomfort and pain are usually associated with these characteristics.

- Endodontic-Periodontic lesions – oral lesions that can potentially form into abscesses. May cause further soreness and pain.

Other possible, less severe, symptoms involve:

- Absent premolars – individuals suffering from otodental syndrome will typically lack the ability to develop premolars due to its genetic related affects.

- Ocular coloboma – an existent hole within the eye of the individual. The hole can be present in either the iris, choroid, optic disc, or retina and is acquired during early/prenatal development. Individuals with these symptoms may exhibit sensitivity to light, blurred vision, and/or blind spots; depending on the size of the missing tissue and its location in the eye.