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.

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.

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.

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.

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

The natural history of MWS is not well known: many patients died in infancy and clinical follow-up has been reported in few surviving adults. However, diagnosis may be more difficult to establish in adults patients, such as: blepharophimosis, contractures, growth retardation, and developmental delay, whereas minor face anomalies are less noticeable as the patient grows older. Throughout the development of the patient from young child to older adult changes the behavior drastically, from kindness to restless and hyperactive to aggressive.

Most of the signs of MWS are present during the neonatal period. The most common signs at this state are multiple congenital joint contractures, dysmorphic features with mask-like face, blepharophimosis, ptosis, micrognathia, cleft or high arched palate, low-set ears, arachnodactyly, chest deformation as pectus, kyphoscoliosis and absent deep tendon reflexes are frequent minor malformations have also been described and consist of renal anomalies, cardiovascular abnormalities, hypospadias, omphalomesenteric duct, hypertriphic pyloric stenosis, duodenal bands, hyoplastic right lower lobe of the lung, displacement of the larynx to the right and vertebral abnormalities, cerebral malformations.

- 75% of children with MWS have blepharophimosis, small mouth, micrognathia, kyphosis/scoliosis, radio ulnar synostose and multiple contractures.

- They have severe developmental delay; congenital joint contractures and blepharophimosis should be present in every patient

- 2 out of 3 of the following signs should be manifested: post natal growth, mask-like faces, retardation, and decreased muscular mass.

- Some may require additional signs such as; micrognathia, high arched or cleft palate, low set ears, kyphoscoliosis.

- The symptoms of MWS are normally diagnosed during the newborn period

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.

The primary symptom of camptocormia is abnormal forward bending of the torso. This bending becomes worse while walking but does not appear when the affected individual is lying down in a horizontal position. This alleviation of the condition indicates that it is a manifestation of another disease or ailment and is not due to a spine that is actually bent. This is somewhat ironic, since the medically accepted name for the condition is bent spine syndrome.

In an afflicted individual, the abnormal bending consists of an anterior flexion greater than 45 degrees. Because of this bending and the physical limitations caused by the conditions associated with the disease, it is usually impossible for an afflicted person to achieve a fully erect position. In addition, patients suffering from camptocormia often experience low back pain as a result of the condition. BSS often appears in individuals afflicted with Parkinson’s disease, muscular dystrophies, endocrine disorders, inflammatory conditions (myositis), or mitochondrial myopathies. As previously mentioned, the disease is more common in older individuals.

When initially identified, camptocormia was classified as a psychogenic disease. Although the condition is sometimes a psychogenic manifestation, camptocormia typically originates from either muscular or neurological diseases. However, due to the wide variety of pathologies resulting in camptocormia, there is no singular cause that is most influential for the condition.

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:

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.

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.

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.

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.

The signs and symptoms of Kaufman oculocerebrofacial syndrome are consistent with the following:

- High palate

- Microcephaly

- Constipation

- Intellectual disability

- Muscular hypotonia

- Nystagmus

Distal spinal muscular atrophy type 2 (DSMA2), also known as Jerash type distal hereditary motor neuropathy (HMN-J) — is a very rare childhood-onset genetic disorder characterised by progressive muscle wasting affecting lower and subsequently upper limbs. The disorder has been described in Arab inhabitants of Jerash region in Jordan as well as in a Chinese family.

The condition is linked to a genetic mutation in the "SIGMAR1" gene on chromosome 19 (locus 19p13.3) and is likely inherited in an autosomal recessive manner.

Electrophysiological evidence of denervation with intact motor and sensory nerve conduction findings must be made by using nerve conduction studies, usually in conjunction with EMG. The presence of polyphasic potentials and fibrillation at rest are characteristic of congenital dSMA.

The following are useful in diagnosis:

- Nerve conduction studies (NCS), to test for denervation

- Electromyography (EMG), also to detect denervation

- X-ray, to look for bone abnormalities

- Magnetic resonance imaging (MRI)

- Skeletal muscle biopsy examination

- Serum creatine kinase (CK) level in blood, usually elevated in affected individuals

- Pulmonary function test

The combination of muscular hypotonia and fixed dilated pupils in infancy is suspicious of Gillespie syndrome. Early onset partial aniridia, cerebellar ataxia, and mental retardation are hallmark of syndrome. The iris abnormality is specific and seems pathognomonic of Gillespie syndrome. The aniridia consisting of a superior coloboma and inferior iris hypoplasia, foveomacular dysplasia.

Atypical Gillespie syndrome associated with bilateral ptosis, exotropia, correctopia, iris hypoplasia, anterior capsular lens opacities, foveal hypoplasia, retinal vascular tortuosity, and retinal hypopigmentation.

Neurological signs ar nystagmus, mild craniofacial asymmetry, axial hypotonia, developmental delay, and mild mental retardation. Mariën P did not support the prevailing view of a global mental retardation as a cardinal feature of Gillespie syndrome but primarily reflect cerebellar induced neurobehavioral dysfunctions following disruption of the cerebrocerebellar anatomical circuitry that closely resembles the "cerebellar cognitive and affective syndrome" (CeCAS).

Congenital pulmonary stenosis and helix dysplasia can be associated.

Children with the Sanjad Sakati syndrome have a triad of:

a) hypoparathyroidism (with episodes of hypocalcemia, hypocalcemic tetany and hypocalcemic seizures.

b) severe mental retardation and

c) dysmorphism.

Typically, children with this syndrome are born low-birth-weight due to intrauterine growth retardation. At birth, there is dysmorphism, which is later typified into the features described below. The child is stunted, often with demonstrable growth hormone deficiency and has moderate to severe mental retardation, mainly as a consequence of repeated seizures brought on by the low blood ionic calcium levels. The immuno-reactive parathormone levels are low to undetectable, with low calcium and high phosphate levels in the blood.

"Dysmorphism" is most evident on the face, with the following features:

- Long narrow face

- Deep-set, small eyes

- Beaked nose

- Large, floppy ears

- Small head (microcephaly) and

- Thin lips with a long philtrum.

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.

Other features include:

- Stunting

- Small hands and feet with long, tapering fingers and clinodactyly

- Dental anomalies in the form of malalignment and malocclusion

In another study of six patients, the patients were investigated further. They were found to have low levels of IGF-1 and markedly retarded bone age.

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.

Spinal muscular atrophy with lower extremity predominance (SMA-LED) is an extremely rare neuromuscular disorder of infants characterised by severe progressive muscle atrophy which is especially prominent in legs.

The disorder is associated with a genetic mutation in the "DYNC1H1" gene (the gene responsible also for one of the axonal types of Charcot–Marie–Tooth disease) and is inherited in an autosomal dominant manner. As with many genetic disorders, there is no known cure to SMA-LED.

The condition was first described in a multi-generational family by Walter Timme in 1917. Its linkage to the "DYNC1H1" gene was discovered in 2010 by M. B. Harms, et al., who also proposed the current name of the disorder.

Fazio–Londe disease (FLD), also called progressive bulbar palsy of childhood, is a very rare inherited motor neuron disease of children and young adults and is characterized by progressive paralysis of muscles innervated by cranial nerves.