The symptoms vary depending on the SMA type, the stage of the disease as well as individual factors. Signs and symptoms below are most common in the severe SMA type 0/I:

- Areflexia, particularly in extremities

- Overall muscle weakness, poor muscle tone, limpness or a tendency to flop

- Difficulty achieving developmental milestones, difficulty sitting/standing/walking

- In small children: adopting of a frog-leg position when sitting (hips abducted and knees flexed)

- Loss of strength of the respiratory muscles: weak cough, weak cry (infants), accumulation of secretions in the lungs or throat, respiratory distress

- Bell-shaped torso (caused by using only abdominal muscles for respiration) in severe SMA type

- Fasciculations (twitching) of the tongue

- Difficulty sucking or swallowing, poor feeding

SMA manifests over a wide range of severity, affecting infants through adults. The disease spectrum is variously divided into 3–5 types, in accordance either with the age of onset of symptoms or with the highest attained milestone of motor development.

The most commonly used classification is as follows:

The most severe form of SMA type I is sometimes termed SMA type 0 (or, severe infantile SMA) and is diagnosed in babies that are born so weak that they can survive only a few weeks even with intensive respiratory support. SMA type 0 should not be confused with SMARD1 which may have very similar symptoms and course but has a different genetic cause than SMA.

Motor development in people with SMA is usually assessed using validated functional scales – CHOP INTEND (The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders) in SMA1; and either the Motor Function Measure scale or one of a few variants of Hammersmith Functional Motor Scale in SMA types 2 and 3.

The eponymous label "Werdnig–Hoffmann disease" (sometimes misspelled with a single "n") refers to the earliest clinical descriptions of childhood SMA by Johann Hoffmann and Guido Werdnig. The eponymous term "Kugelberg–Welander disease" is after Erik Klas Hendrik Kugelberg (1913-1983) and Lisa Welander (1909-2001), who distinguished SMA from muscular dystrophy. Rarely used "Dubowitz disease" (not to be confused with Dubowitz syndrome) is named after Victor Dubowitz, an English neurologist who authored several studies on the intermediate SMA phenotype.

In all spinal muscular atrophies, the primary feature is muscle weakness accompanied by atrophy of muscle. This is the result of denervation, or loss of the signal to contract that is transmitted by the motor neurons in the spinal cord. The signal is normally transmitted from the spinal cord to muscle via the motor neuron's axon, but in spinal muscular atrophies either the entire motor neuron or the motor neuron's axon loses the ability to transmit signals to muscles.

The symptoms are strongly related to the exact disease (see above) and, sometimes, to the age of onset. Certain conditions (e.g., spinal muscular atrophy or spinal and bulbar muscular atrophy) have a wide range, from infancy to adult, fatal to trivial, with different affected individuals manifesting every shade of impairment between these two extremes. Other muscular atrophies have a different and often very severe course. Some of them are extremely rare and described only in a handful of individuals. However, in all cases the majority of symptoms are a consequence of muscle weakness.

Based on the type of muscles affected, spinal muscular atrophies can be divided into:

- "Proximal spinal muscular atrophies", i.e., conditions that affect primarily proximal muscles;

- "Distal spinal muscular atrophies" (which significantly overlap with distal hereditary motor neuronopathies) where they affect primarily distal muscles.

When taking into account prevalence, spinal muscular atrophies are traditionally divided into:

- "Autosomal recessive proximal spinal muscular atrophy", responsible for 90-95% of cases and usually called simply "spinal muscular atrophy" (SMA) – a disorder associated with a genetic mutation on the "SMN1" gene on chromosome 5q (locus 5q13), affecting people of any age but in its most severe form being the most common genetic cause of infant death;

- "Localised spinal muscular atrophies" – much more rare conditions, in some instances described in but a few patients in the world, which are associated with mutations of genes other than "SMN1" and for this reason sometimes termed simply "non-5q spinal muscular atrophies".

A more detailed classification is based on the gene associated with the condition (where identified) and is presented in table below.

In all forms of SMA (with an exception of X-linked spinal muscular atrophy type 1), only motor neurons, located at the anterior horn of spinal cord, are affected; sensory neurons, which are located at the posterior horn of spinal cord, are not affected. By contrast, hereditary disorders that cause both weakness due to motor denervation along with "sensory" impairment due to sensory denervation are known as hereditary motor and sensory neuropathies (HMSN).

Usually, the first respiratory symptoms are dyspnea and paradoxical respirations which then escalate within the first few months of life to diaphragmatic paralysis. The symptoms of diaphragmatic paralysis come on very rapidly and without warning, and the patient is often rushed to a hospital where they are placed on a ventilator for respiratory support. Due to the severe nature of diaphragmatic paralysis the patient eventually needs continuous ventilation support to survive. Continuous ventilation, however, may in itself cause damage to the anatomy of the lungs.

In addition to diaphragmatic paralysis other issues may arise: as the name suggests, the distal limbs are most affected with symptoms of weakness, restricting mobility due to (near-)paralysis of the distal limbs as well as the head and neck. Also, dysfunction of the peripheral nerves and the autonomic nervous system may occur. Due to these dysfunctions the patients have been shown to suffer from excessive sweating and irregular heartbeat. The deep tendon reflex is also lost in patients with DSMA1.

Uterine growth retardation and poor foetal movement have been observed in severe DSMA1 cases.

Individuals with SBMA have muscle cramps and progressive weakness due to degeneration of motor neurons in the brain stem and spinal cord. Ages of onset and severity of manifestations in affected males vary from adolescence to old age, but most commonly develop in middle adult life. The syndrome has neuromuscular and endocrine manifestations.

DSMA1 was identified and classified as a sub-group of spinal muscular atrophies (SMA) in 1974. Currently, various classifications include DSMA1 among general spinal muscular atrophies or distal hereditary motor neuropathies, though the latter has been argued to be more correct.

X-linked spinal muscular atrophy type 2 (SMAX2, XLSMA), also known as arthrogryposis multiplex congenita X-linked type 1 (AMCX1), is a rare neurological disorder involving death of motor neurons in the anterior horn of spinal cord resulting in generalised muscle wasting (atrophy). The disease is caused by a mutation in "UBA1" gene and is passed in a X-linked recessive manner by carrier mothers to affected sons.

Affected babies have general muscle weakness, weak cry and floppy limbs; consequently, the condition is usually apparent at or even before birth. Symptoms resemble the more severe forms of the more common spinal muscular atrophy (SMA); however, SMAX2 is caused by a different genetic defect and only genetic testing can correctly identify the disease.

The disorder is usually fatal in infancy or early childhood due to progressive respiratory failure, although survival into teenage years have been reported. As with many genetic disorders, there is no known cure to SMAX2. Appropriate palliative care may be able to increase quality of life and extend lifespan.

Early signs often include weakness of tongue and mouth muscles, fasciculations, and gradually increasing weakness of limb muscles with muscle wasting. Neuromuscular management is supportive, and the disease progresses very slowly, but can eventually lead to extreme disability. Further signs and symptoms include:

As a result of lower motor neurone degeneration, the symptoms of PMA include:

- atrophy

- fasciculations

- muscle weakness

Some patients have symptoms restricted only to the arms or legs (or in some cases just one of either). These cases are referred to as "Flail Arm" (FA) or "Flail Leg" (FL) and are associated with a better prognosis.

Often, every joint in a patient with arthrogryposis is affected; in 84% all limbs are involved, in 11% only the legs, and in 4% only the arms are involved. Every joint in the body, when affected, displays typical signs and symptoms: for example, the shoulder (internal rotation); wrist (volar and ulnar); hand (fingers in fixed flexion and thumb in palm); hip (flexed, abducted and externally rotated, frequently dislocated); elbow (extension and pronation) and foot (clubfoot). Range of motion can be different between joints because of the different deviations. Some types of arthrogryposis like amyoplasia have a symmetrical joint/limb involvement, with normal sensations. The contractures in the joints can result in delayed walking development in the first 5 years, but severity of contractures do not necessarily predict eventual walking ability or inability.

Intelligence is normal to above normal in children with amyoplasia, but it is not known how many of these children have an above normal intelligence, and there is no literature available about the cause of this syndrome. There are a few syndromes like the Freeman-Sheldon and Gordon syndrome, which have craniofacial involvement. The amyoplasia form of arthrogryposis is sometimes accompanied with a midline facial hemangioma.

Arthrogryposis is not a diagnosis but a clinical finding, so this disease is often accompanied with other syndromes or diseases. These other diagnoses could affect any organ in a patient. There are a few slightly more common diagnoses such as pulmonary hypoplasia, cryptorchidism, congenital heart defects, tracheoesophageal fistulas, inguinal hernias, cleft palate, and eye abnormalities.

In contrast to amyotrophic lateral sclerosis or primary lateral sclerosis, PMA is distinguished by the "absence" of:

- brisk reflexes

- spasticity

- Babinski's sign

- Emotional lability

In terms of the signs/symptoms of Fukuyama congenital muscular dystrophy it is characterized by a decrease in skeletal muscle tone as well as an impairment in brain and eye development.Initial symptoms of FCMD present in early infancy as decreased ability to feed. Marked differences in facial appearance occur due to decreased muscle tone. Further characteristics include:

- Seizures

- Delay in developmental

- Cardiac issues

- Swallowing difficulty

- Neurological problems

Fukuyama congenital muscular dystrophy also affects the nervous system and various associated parts. FCMD affects normal development of the brain producing a broadly smooth, bumpy shaped cortex named cobblestone lissencephaly as well as various other malformations, notably micropolygyria. Children also experience delayed myelination in the brain.

"Disuse atrophy" of muscles and bones, with loss of mass and strength, can occur after prolonged immobility, such as extended bedrest, or having a body part in a cast (living in darkness for the eye, bedridden for the legs etc.). This type of atrophy can usually be reversed with exercise unless severe. Astronauts in microgravity must exercise regularly to minimize atrophy of their limb muscles.

There are many diseases and conditions which cause atrophy of muscle mass. For example, diseases such as cancer and AIDS induce a body wasting syndrome called "cachexia", which is notable for the severe muscle atrophy seen. Other syndromes or conditions which can induce skeletal muscle atrophy are congestive heart failure and liver disease.

During aging, there is a gradual decrease in the ability to maintain skeletal muscle function and mass. This condition is called "sarcopenia", and may be distinct from atrophy in its pathophysiology. While the exact cause of sarcopenia is unknown, it may be induced by a combination of a gradual failure in the "satellite cells" which help to regenerate skeletal muscle fibers, and a decrease in sensitivity to or the availability of critical secreted growth factors which are necessary to maintain muscle mass and satellite cell survival.

Pathologic atrophy of muscles can occur with diseases of the motor nerves, or diseases of the muscle tissue itself. Examples of atrophying nerve diseases include Charcot-Marie-Tooth disease, poliomyelitis, amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), and Guillain–Barré syndrome. Examples of atrophying muscle diseases include muscular dystrophy, myotonia congenita, and myotonic dystrophy.

Changes in Na+ channel isoform expression and spontaneous activity in muscle called fibrillation can also result in muscle atrophy.

Patient feels contracture of middle and ring finger. Slight thinning of the subdigital Palm of the affected fingers. Initial pain and weakness subside with preliminary treatment with antiinflammatories, and B-complex vitamins. Initial loss of function improves almost fully.

FLD produces rapidly progressive weakness of tongue, face and pharyngeal muscles in a clinical pattern similar to myasthenia. Neuromuscular transmission may be abnormal in these muscles because of rapid denervation and immature reinnervation. Paralysis occurs secondary to degeneration of the motor neurons of the brain stem. It causes progressive bulbar paralysis due to involvement of motor neurons of the cranial nerve nuclei. The most frequent symptoms at onset of progressive bulbar paralysis of childhood has been a unilateral facial paralysis. It is followed in frequency by dysarthria due to facial weakness or by dysphagia. Palatal weakness and palpebral ptosis also have been reported in few patients. Both sexes can be affected.

Most infants with CMD will display some progressive muscle weakness or muscle wasting (atrophy), although there can be different degrees and symptoms of severeness of progression. The weakness is indicated as "hypotonia", or lack of muscle tone, which can make an infant seem unstable.

Children may be slow with their motor skills; such as rolling over, sitting up or walking, or may not even reach these milestones of life. Some of the more rarer forms of CMD can result in significant learning disabilities.

Neuropathy disorders usually have onset in childhood or young adulthood. Motor symptoms seem to be more predominant that sensory symptoms. Symptoms of these disorders include: fatigue, pain, lack of balance, lack of feeling, lack of reflexes, and lack of sight and hearing, which result from muscle atrophy. Patients can also suffer from high arched feet, hammer toes, foot drop, foot deformities, and scoliosis. These symptoms are a result of severe muscular weakness and atrophy. In patients suffering from demyelinating neuropathy, symptoms are due to slow nerve conduction velocities, however people with axonal degradation have average to normal nerve conduction velocities.

Congenital distal spinal muscular atrophy (congenital dSMA) is a hereditary genetic condition characterized by muscle wasting (atrophy), particularly of distal muscles in legs and hands, and by early-onset contractures (permanent shortening of a muscle or joint) of the hip, knee, and ankle. Affected individuals often have shorter lower limbs relative to the trunk and upper limbs. The condition is a result of a loss of anterior horn cells localized to lumbar and cervical regions of the spinal cord early in infancy, which in turn is caused by a mutation of the "TRPV4" gene. The disorder is inherited in an autosomal dominant manner. Arm muscle and function, as well as cardiac and respiratory functions are typically well preserved.

Centronuclear myopathies (CNM) are a group of congenital myopathies 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.

Symptoms of CNM include severe hypotonia, hypoxia-requiring breathing assistance, and scaphocephaly. Among centronuclear myopathies, the X-linked myotubular myopathy form typically presents at birth, and is thus considered a congenital myopathy. However, some centronuclear myopathies may present later in life.

Monomelic amyotrophy (MMA), also known as Hirayama disease and Spinal muscular atrophy juvenile nonprogressive — is an untreatable, focal motor neuron disease that primarily affects young (15- to 25-year-old) males in India and Japan. MMA is marked by insidious onset of muscular atrophy, which stabilizes at a plateau after two to five years from which it neither improves nor worsens. There is no pain or sensory loss associated with MMA. Unlike other lower motor neuron diseases, MMA is not believed to be hereditary and fasciculations (involuntary muscle twitches) are rare.EMG tests reveal loss of the nerve supply, or denervation, in the affected limb without "conduction block" (nerve blockage restricted to a small segment of the nerve). Increased sweating, coldness and cyanosis have been reported for a few patients, indicating involvement of the sympathetic nervous system.While MMA will cause weakness and/or wasting in only one limb, EMG and NCV tests often show signs of reinnervation in the unaffected limbs.

Arthrogryposis multiplex congenital (AMC), or simply arthrogryposes, describes congenital joint contracture in two or more areas of the body. It derives its name from Greek, literally meaning "curving of joints" (', "joint"; ', late Latin form of late Greek "", "hooking"). Children born with one or more joint contractures have abnormal fibrosis of the muscle tissue causing muscle shortening, and therefore are unable to perform active extension and flexion in the affected joint or joints. AMC has been divided into three groups: amyoplasia, distal arthrogryposis, and syndromic. Amyoplasia is characterized by severe joint contractures and muscle weakness. Distal arthrogryposis mainly involves the hands and feet. Types of arthrogryposis with a primary neurological or muscle disease belong to the syndromic group.

Fukuyama congenital muscular dystrophy (FCMD) is a rare, autosomal recessive form of muscular dystrophy (weakness and breakdown of muscular tissue) mainly described in Japan but also identified in Turkish and Ashkenazi Jewish patients, fifteen cases were first described on 1960 by Fukuyama.

FCMD mainly affects the brain, eyes, and muscles, in particular, the disorder affects development of the skeletal muscles leading to weakness and deformed appearances, and brain development is blunted affecting cognitive functioning as well as social skills. In 1995, the disorder was linked to mutations in a gene coding for the protein fukutin (the "FCMD" gene). Fukuyama congenital muscular dystrophy is the second most prevalent form of muscular dystrophy in Japan. One out of every 90 people in Japan is a heterozygous carrier.

Clinical signs and symptoms depend on which spinal cord level (cervical, thoracic or lumbar) is affected and the extent (anterior, posterior or lateral) of the pathology, and may include:

- upper motor neuron signs—weakness, spasticity, clumsiness, altered tonus, hyperreflexia and pathological reflexes, including Hoffmann's sign and inverted Plantar reflex (positive Babinski sign);

- lower motor neuron signs—weakness, clumsiness in the muscle group innervated at the level of spinal cord compromise, muscle atrophy, hyporeflexia, muscle hypotonicity or flaccidity, fasciculations;

- sensory deficits;

- bowel/bladder symptoms and sexual dysfunction.