Disease onset is typically in early infancy but may occur later in life. Children who have the classic form of Farber disease develop symptoms within the first few weeks of life. These symptoms may include moderately impaired mental ability and problems with swallowing. The liver, heart and kidneys may also be affected. Other symptoms may include vomiting, arthritis, swollen lymph nodes, swollen joints, joint contractures (chronic shortening of muscles or tendons around joints), hoarseness and xanthomas which thicken around joints as the disease progresses. Patients with breathing difficulty may require a breathing tube.

Presentation of symptoms and signs varies considerably by form (DM1/DM2), severity and even unusual DM2 phenotypes. DM1 symptoms for DM2 include problems with executive function (e.g., organization, concentration, word-finding) and hypersomnia. Conduction abnormalities are more common in DM1 than DM2, but all people are advised to have an annual ECG. Both types are also associated with insulin resistance. Myotonic dystrophy may have a cortical cataract with a blue dot appearance, or a posterior subcapsular cataract.

DM2 is generally milder than DM1, with generally fewer DM2 people requiring assistive devices than DM1 people. In addition, the severe congenital form that affects babies in DM1 has not been found in DM2 and the early onset of symptoms is rarely noted to appear in younger people in the medical literature.

Symptoms may appear at any time from infancy to adulthood. DM causes general weakness, usually beginning in the muscles of the hands, feet, neck, or face. It slowly progresses to involve other muscle groups, including the heart. DM affects a wide variety of other organ systems as well.

Myotonic dystrophy is a long term genetic disorder that affects muscle function. Symptoms include gradually worsening muscle loss and weakness. Muscles often contract and are unable to relax. Other symptoms may include cataracts, intellectual disability, and heart conduction problems. In men there may be early balding and an inability to have children.

Myotonic dystrophy is an autosomal-dominant disorder which is typically inherited from a person's parents. There are two main types: type 1 (DM1) due to mutations in the DMPK gene and type 2 (DM2) due to mutations in the CNBP gene. The disorder generally worsens in each generation. A type of DM1 may be apparent at birth. DM2 is generally milder. They are types of muscular dystrophy. Diagnosis is confirmed by genetic testing.

There is no cure. Treatments may include braces or wheelchairs, pacemakers, and non invasive positive pressure ventilation. The medications mexiletine or carbamazepine are occasionally helpful. Pain if it occurs may be treated with tricyclic antidepressants and nonsteroidal anti inflammatory drugs (NSAIDs).

Myotonic dystrophy affects more than 1 in 8,000 people worldwide. While myotonic dystrophy can occur at any age, onset is typically in the 20s and 30s. It is the most common form of muscular dystrophy that begins in adulthood. It was first described in 1909 with the underlying cause of type 1 determined in 1992.

Clinical:

Patients often present with a history of fever of unknown origin, muscular weakness, poor development, abnormal dentition, normal serum calcium, phosphorus, and alkaline phosphatase levels. Associated clinical findings also include glaucoma, photosensitivity, heart block, foot deformities, and chronic psoriasiform skin lesions.

Radiological:

Classic radiologic findings were first described by Edward B. Singleton and David Merten in 1973.

Typical radiographic appearances include skeletal demineralization, expanded shafts of the metacarpals and phalanges with widenend medullary cavities, cardiomegaly, and intramural calcification of the proximal aorta with occasional extension into the aortic or mitral valves.

Other commonly seen radiographic findings include shallow acetabular fossa, subluxation of the femoral head, coxa valga, hypoplastic radial epiphysis, soft tissue calcifications between the radius and ulna, constriction of the proximal radial shaft, acro-osteolysis, and equinovarus foot deformities.

Classic phosphofructokinase deficiency is the most common type of this disorder. This type presents with exercise-induced muscle cramps and weakness (sometimes rhabdomyolysis), myoglobinuria, as well as with haemolytic anaemia causing dark urine a few hours later.

Hyperuricemia is common, due to the kidneys' inability to process uric acid following damage resulting from processing myoglobin. Nausea and vomiting following strenuous exercise is another common indicator of classic PFK deficiency. Many patients will also display high levels of bilirubin, which can lead to a jaundiced appearance. Symptoms for this type of PFK deficiency usually appear in early childhood.

Human PFK deficiency is categorized into four types: classic, late-onset, infantile and hemolytic. These types are differentiated by age at which symptoms are observed and which symptoms present.

Farber disease (also known as Farber's lipogranulomatosis, ceramidase deficiency, "Fibrocytic dysmucopolysaccharidosis," and "Lipogranulomatosis") is an extremely rare (80 cases reported worldwide to this day) autosomal recessive lysosomal storage disease marked by a deficiency in the enzyme ceramidase that causes an accumulation of fatty material sphingolipids leading to abnormalities in the joints, liver, throat, tissues and central nervous system. Normally, the enzyme ceramidase breaks down fatty material in the body’s cells. In Farber Disease, the gene responsible for making this enzyme is mutated. Hence, the fatty material is never broken down and, instead, accumulates in various parts of the body, leading to the signs and symptoms of this disorder.

Singleton Merten Syndrome is an autosomal dominate genetic disorder with variable expression with an onset of symptoms during childhood.

Sandhoff disease symptoms are clinically indeterminable from Tay–Sachs disease. The classic infantile form of the disease has the most severe symptoms and is incredibly hard to diagnose at this early age. The first signs of symptoms begin before 6 months of age and the parents’ notice when the child begins regressing in their development. If the children had the ability to sit up by themselves or crawl they will lose this ability. This is caused by a slow deterioration of the muscles in the child’s body from the buildup of GM2 gangliosides. Since the body is unable to create the enzymes it needs within the central nervous system it is unable to attach to these gangliosides to break them apart and make them non-toxic. With this buildup there are several symptoms that begin to appear such as muscle/motor weakness, sharp reaction to loud noises, blindness, deafness, inability to react to stimulants, respiratory problems and infections, mental retardation, seizures, cherry red spots in the retina, enlarged liver and spleen (hepatosplenomegaly), pneumonia, or bronchopneumonia.

The other two forms of Sandhoff disease have similar symptoms but to a lesser extent. Adult and juvenile forms of Sandhoff disease are more rare than the infantile form. In these cases victims suffer cognitive impairment (retardation) and a loss of muscle coordination that impairs and eventually destroys their ability to walk; the characteristic red spots in the retina also develop. The adult form of the disease, however, is sometimes milder, and may only lead to muscle weakness that impairs walking or the ability to get out of bed.

Since the original identification of Schimmelpenning syndrome, the number of findings has expanded to the point that the syndrome is associated with a considerable constellation of abnormalities. The abnormalities may occur in a variety of combinations, and need not include all three aspects of the classic triad of sebaceous nevus, seizures and mental retardation. In 1998, a literature review by van de Warrenburg et al. found:

- seizures in 67% of cases

- mental retardation in 61% of cases

- ophthalmological abnormalities in 59% of cases

- involvement of other organ systems in 61% of cases

- structural abnormality of cerebrum or cranium in 72% of cases

The major neurological abnormalities include mental retardation to varying extent, seizures, and hemiparesis. Seizures, when present, typically begin during the first year of life. The most common structural central nervous system abnormalities in Schimmelpenning syndrome are hemimegalencephaly and ipselateral gyral malformations.

The major ocular abnormalities are colobomas and choristomas.

Skeletal abnormalities may include dental irregularities, scoliosis, vitamin D-resistant rickets and hypophosphatemia. Cardiovascular abnormalities include ventricular septal defect and co-arctation of the aorta; urinary system issues include horseshoe kidney and duplicated urinary collection system.

Sandhoff disease, also known as Sandhoff–Jatzkewitz disease, variant 0 of GM2-Gangliosidosis or Hexosaminidase A and B deficiency, is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, its derivative GA2, the glycolipid globoside in visceral tissues, and some oligosaccharides. Accumulation of these metabolites leads to a progressive destruction of the central nervous system and eventually to death. The rare autosomal recessive neurodegenerative disorder is clinically almost indistinguishable from Tay–Sachs disease, another genetic disorder that disrupts beta-hexosaminidases A and S. There are three subsets of Sandhoff disease based on when first symptoms appear: classic infantile, juvenile and adult late onset.

Infants with Catel–Manzke syndrome have an extra (supernumerary), irregularly shaped bone known as a Hyperphalangy located between the first bone of the index finger (proximal phalanx) and the corresponding bone within the body of the hand (second metacarpal). As a result, the index fingers may be fixed in an abnormally bent position (clinodactyly). In some rare cases, additional abnormalities of the hands may also be present. Due to the presence of micrognathia, glossoptosis, and cleft palate, affected infants may have feeding and breathing difficulties; growth deficiency; consistent middle ear infections (otitis media); and other complications.

In addition, some infants with the syndrome may have structural abnormalities of the heart that are present at birth (congenital heart defects). The range and severity of symptoms and findings may vary from case to case. Catel–Manzke syndrome usually appears to occur randomly, for unknown sporadic reasons.

Infantile myofibromatosis (also known as "Congenital generalized fibromatosis," and "Congenital multicentric fibromatosis") is the most common fibrous tumor of infancy, in which eighty percent of patients have solitary lesions with half of these occurring on the head and neck, and 60% are present at or soon after birth. Less commonly, infantile myofibromatosis presents as multiple lesions of skin, muscle, and bone with about 1/3 of these cases also having lesions in their visceral organs. All of these cases have an excellent prognosis with their tumors sometimes regressing spontaneously except for those cases in which there is visceral involvement where the prognosis is poor. Infantile myofibromatosis and the classic form of mesoblastic nephroma have been suggested to be the same disease because of their very similar histology. However, studies on the distribution of cell-type markers (i.e. cyclin D1 and Beta-catenin) indicate that the two neoplasms likely have different cellular origins.

Schimmelpenning syndrome is a neurocutaneous condition characterized by one or more sebaceous nevi, usually appearing on the face or scalp, associated with anomalies of the central nervous system, ocular system, skeletal system, cardiovascular system, and genitourinary system.

Synonyms include: "Linear nevus sebaceous syndrome (LNSS)", "Schimmelpenning-Feuerstein-Mims syndrome", "Feuerstein-Mims syndrome", "sebaceous nevus syndrome", "Solomon syndrome", and "Jadassohn's nevus phakomatosis". "Nevus" is sometimes spelled "naevus" and "sebaceous" may also be spelled "sebaceus". "Epidermal nevus syndrome" is sometimes used as a synonym, but more often as a broader term referring to Schimmelpenning syndrome in addition to nevus comedonicus syndrome, CHILD syndrome, Becker's nevus syndrome, and phakomatosis pigmentokeratotica.

The classic Schimmelpenning syndrome diagnosis comprises a triad of sebaceous nevi, seizures, and mental retardation. The condition was first reported by Gustav Schimmelpenning in 1957 and independently reported by Feuerstein and Mims in 1962.

Catel–Manzke syndrome is a rare genetic disorder characterized by distinctive abnormalities of the index fingers; the classic features of Pierre Robin syndrome; occasionally with additional physical findings. "Pierre Robin syndrome" refers to a sequence of abnormalities that may occur as a distinct syndrome or as part of another underlying disorder. Pierre Robin syndrome is characterized by an unusually small jaw (micrognathia), downward displacement or retraction of the tongue (glossoptosis), and incomplete closure of the roof of the mouth (cleft palate). It is also linked to hyper mobility syndrome.

It is characterized by developmental defects including cryptophthalmos (where the eyelids fail to separate in each eye), and malformations in the genitals (such as micropenis, cryptorchidism or clitoromegaly). Congenital malformations of the nose, ears, larynx and renal system, as well as mental retardation, manifest occasionally. Syndactyly (fused fingers or toes) has also been noted.

As with several other metabolic conditions, OTC deficiency can have variable presentations, regarding age of onset and the severity of symptoms. This compounded when considering heterozygous females and the possibility of non-random X-inactivation. In the classic and most well-known presentation, a male infant appears well initially, but by the second day of life they are irritable, lethargic and stop feeding. A metabolic encephalopathy develops, and this can progress to coma and death without treatment. Ammonia is only toxic to the brain, other tissues can handle elevated ammonia concentrations without problems.

Later onset forms of OTC deficiency can have variable presentations. Although late onset forms of the disease are often considered milder than the classic infantile presentation, any affected individual is at risk for an episode of hyperammonemia that could still be life-threatening, if presented with the appropriate stressors. These patients will often present with headaches, nausea, vomiting, delayed growth and a variety of psychiatric symptoms (confusion, delirium, aggression, or self-injury). A detailed dietary history of an affected individual with undiagnosed OTC deficiency will often reveal a history of protein avoidance.

The prognosis of a patient with severe OTC deficiency is well correlated with the length of the hyperammonemic period rather than the degree of hyperammonemia or the presence of other symptoms, such as seizures. Even for patients with late onset forms of the disease, their overall clinical picture is dependent on the extent of hyperammonemia they have experienced, even if it has remained unrecognized.

Various eye abnormalities are often seen including lenticonus, keratoconus, cataracts as well as retinal flecks in the macula and mid-periphery. These rarely threaten vision. Lenticonus (cone-shaped lens) can be treated by replacement of the lens, as for cataracts. Mild keratoconus can be treated with hard or piggy-back contact lenses; severe cases may require a corneal transplant.

Diffuse leiomyomatosis of the esophagus and tracheobronchial tree has been reported in some families with Alport syndrome. Symptoms usually appear in late childhood and include dysphagia, postprandial vomiting, substernal or epigastric pain, recurrent bronchitis, dyspnea, cough, and stridor. Leiomyomatosis is confirmed by computed tomography (CT) scanning or magnetic resonance imaging (MRI).

Pterygium unguis (also known as "Dorsal pterygium") forms as a result of scarring between the proximal nailfold and matrix, with the classic example being lichen planus, though it has been reported to occur as a result of sarcoidosis and Hansen's disease.

Fraser syndrome (also known as Meyer-Schwickerath's syndrome, Fraser-François syndrome, or Ullrich-Feichtiger syndrome) is an autosomal recessive congenital disorder. Fraser syndrome is named for the geneticist George R. Fraser, who first described the syndrome in 1962.

Eagle syndrome (also termed stylohyoid syndrome styloid syndrome, styloid-stylohyoid syndrome, or styloid–carotid artery syndrome) is a rare condition commonly characterized but not limited to - sudden, sharp nerve-like pain in the jaw bone and joint, back of the throat, and base of the tongue, triggered by swallowing, moving the jaw, or turning the neck. Since the brain to body's nerve connections pass through the neck; many seemingly random symptoms can be triggered by impingement or entanglement. First described by American otorhinolaryngologist Watt Weems Eagle in 1937, the condition is caused by an elongated or misshapen styloid process, the slender, pointed piece of bone just below the ear, and/or calcification of the stylohyoid ligament, which interferes with the functioning of neighboring regions in the body, giving rise to pain.

Possible symptoms include:

Classic eagle syndrome is present on only one side, however, rarely, it may be present on both sides.

In vascular eagle syndrome, the elongated styloid process comes in contact with the internal carotid artery below the skull. In these cases, turning the head can cause compression of the artery or a tear inside the blood vessel, which restricts blood flow and can potentially lead to a transient ischemic attack (TIA) or stroke.

Ornithine transcarbamylase deficiency also known as OTC deficiency is the most common urea cycle disorder in humans. Ornithine transcarbamylase, the defective enzyme in this disorder is the final enzyme in the proximal portion of the urea cycle, responsible for converting carbamoyl phosphate and ornithine into citrulline. OTC deficiency is inherited in an X-linked recessive manner, meaning males are more commonly affected than females.

In severely affected individuals, ammonia concentrations increase rapidly causing ataxia, lethargy and death without rapid intervention. OTC deficiency is diagnosed using a combination of clinical findings and biochemical testing, while confirmation is often done using molecular genetics techniques.

Once an individual has been diagnosed, the treatment goal is to avoid precipitating episodes that can cause an increased ammonia concentration. The most common treatment combines a low protein diet with nitrogen scavenging agents. Liver transplant is considered curative for this disease. Experimental trials of gene therapy using adenoviral vectors resulted in the death of one participant, Jesse Gelsinger, and have been discontinued.

Duarte galactosemia (also known as Duarte variant galactosemia, DG, or biochemical variant galactosemia) is an inherited condition associated with diminished ability to metabolize galactose due to a partial deficiency of the enzyme galactose-1-phosphate uridylyltransferase. Duarte galactosemia (DG) is estimated to affect close to one in 4,000 infants born in the United States. DG Is considered by most healthcare professionals to be clinically mild. It differs from classic galactosemia in that patients with Duarte galactosemia have partial GALT deficiency whereas patients with classic galactosemia have complete, or almost complete, GALT deficiency.

DG, and the possible outcomes associated with this condition, are currently not well understood. Due to regional variations in newborn screening (NBS) protocols, some infants with DG are identified by NBS but others are not. In addition, of the infants who are diagnosed, most are clinically healthy as babies and toddlers, resulting in early discharge from follow up. Many healthcare professionals believe that DG does not negatively impact development. However, some reports have indicated that children with DG may be at increased risk for some developmental problems.