Due to the wide range of genetic disorders that are presently known, diagnosis of a genetic disorder is widely varied and dependent of the disorder. Most genetic disorders are diagnosed at birth or during early childhood, however some, such as Huntington's disease, can escape detection until the patient is well into adulthood.

The basic aspects of a genetic disorder rests on the inheritance of genetic material. With an in depth family history, it is possible to anticipate possible disorders in children which direct medical professionals to specific tests depending on the disorder and allow parents the chance to prepare for potential lifestyle changes, anticipate the possibility of stillbirth, or contemplate termination. Prenatal diagnosis can detect the presence of characteristic abnormalities in fetal development through ultrasound, or detect the presence of characteristic substances via invasive procedures which involve inserting probes or needles into the uterus such as in amniocentesis.

Not all genetic disorders directly result in death, however there are no known cures for genetic disorders. Many genetic disorders affect stages of development such as Down syndrome. While others result in purely physical symptoms such as muscular dystrophy. Other disorders, such as Huntington's disease show no signs until adulthood. During the active time of a genetic disorder, patients mostly rely on maintaining or slowing the degradation of quality of life and maintain patient autonomy. This includes physical therapy, pain management, and may include a selection of alternative medicine programs.

Elevated levels of serum cholestanol are diagnostic of CTX. Alternatively analysis of 27-hydroxycholesterol and 7 alpha hydroxycholesterol can be used. Genetic testing of the CYP27A1 gene is confirmatory and is increasingly being used as a first line test as part of symptom specific gene panels (genetic eye disease, ataxia, dementia).

There are two types of this inherited condition, "glycogen storage disease IXa1" and "glycogen storage disease IXa2" that affect the liver of an individual. Mutations in PHKA2 have been seen in individuals with glycogen storage disease IXa2.

The diagnosis of glycogen storage disease IX consists of the following:

- Complete blood count

- Urinalysis

- Histological study of the liver (via biopsy)

- Genetic testing

- Physical exam

The diagnosis of Mulibrey nanism can be done via genetic testing, as well as by the physical characteristics (signs/symptoms) displayed by the individual.

The diagnosis of oculopharyngeal muscular dystrophy can be done via two methods, a muscle biopsy or a blood draw with genetic testing for GCG trinucleotide expansions in the PABPN1 gene. The genetic blood testing is more common.Additionally, a distinction between OPMD and myasthenia gravis or mitochondrial myopathy must be made, in regards to the differential diagnosis of this condition.

The standard treatment is chenodeoxycholic acid (CDCA) replacement therapy. Serum cholesterol levels are also followed. If hypercholesterolemia is not controlled with CDCA, an HMG-CoA reductase inhibitor ("statins" such as simvastatin) can also be used.

Once a diagnosis is made, the treatment is based on an individual’s clinical condition and may include standard management for autoimmunity and immunodeficiency. Hematopoietic stem cell transplantation has cured the immune abnormalities in one TRIANGLE patient, although the neurodevelopmental delay would likely remain. Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.

In a sample of 19 children, a 1997 study found that 3 died before the age of 3, and 2 never learned to walk. The children had various levels of delayed development with developmental quotients from 60 to 85.

For the diagnosis of congenital muscular dystrophy, the following tests/exams are done:

- Lab study (CK levels)

- MRI (of muscle, and/or brain)

- EMG

- Genetic testing

Though it is only definitively diagnosed by a genetic test, autosomal dominant porencephaly type I can be suspected if the disease is known to run in the family or if someone shows symptoms. CT scanning or MRI may be useful in indicating a diagnosis. COL4A1 may be mutated in other diseases that need to be distinguished, including brain small vessel disease with hemorrhage and HANAC syndrome. CADASIL syndrome is caused by a mutation in a different gene, but may cause similar symptoms. Sporadic porencephaly is another disorder that can appear similar.

The subtypes of congenital muscular dystrophy have been established through variations in multiple genes. It should be noted that phenotype, as well as, genotype classifications are used to establish the subtypes, in some literature.

One finds that congenital muscular dystrophies can be either autosomal dominant or autosomal recessive in terms of the inheritance pattern, though the latter is much more common

Individuals who suffer from congenital muscular dystrophy fall into one of the following "types":

Electrodiagnostic testing (also called electrophysiologic) includes nerve conduction studies which involves stimulating a peripheral motor or sensory nerve and recording the response, and needle electromyography, where a thin needle or pin-like electrode is inserted into the muscle tissue to look for abnormal electrical activity.

Electrodiagnostic testing can help distinguish myopathies from neuropathies, which can help determine the course of further work-up. Most of the electrodiagnostic abnormalities seen in myopathies are also seen in neuropathies (nerve disorders). Electrodiagnostic abnormalities common to myopathies and neuropathies include; abnormal spontaneous activity (e.g., fibrillations, positive sharp waves, etc.) on needle EMG and, small amplitudes of the motor responses compound muscle action potential, or CMAP during nerve conduction studies. Many neuropathies, however, cause abnormalities of sensory nerve studies, whereas myopathies involve only the muscle, with normal sensory nerves. The most important factor distinguishing a myopathy from a neuropathy on needle EMG is the careful analysis of the motor unit action potential (MUAP) size, shape, and recruitment pattern.

There is substantial overlap between the electrodiagnostic findings the various types of myopathy. Thus, electrodiagnostic testing can help distinguish neuropathy from myopathy, but is not effective at distinguishing which specific myopathy is present, here muscle biopsy and perhaps subsequent genetic testing are required.

As with most genetic diseases there is no way to prevent the entire disease. With prompt recognition and treatment of infections in childhood, the complications of low white blood cell counts may be limited.

X-linked myotubular myopathy (MTM) is a form of centronuclear myopathy (CNM) associated with myotubularin 1.

Genetically inherited traits and conditions are often referred to based upon whether they are located on the "sex chromosomes" (the X or Y chromosomes) versus whether they are located on "autosomal" chromosomes (chromosomes other than the X or Y). Thus, genetically inherited conditions are categorized as being sex-linked (e.g., X-linked) or autosomal. Females have two X-chromosomes, while males only have a single X chromosome, and a genetic abnormality located on the X chromosome is much more likely to cause clinical disease in a male (who lacks the possibility of having the normal gene present on any other chromosome) than in a female (who is able to compensate for the one abnormal X chromosome).

The X-linked form of MTM is the most commonly diagnosed type. Almost all cases of X-linked MTM occurs in males. Females can be "carriers" for an X-linked genetic abnormality, but usually they will not be clinically affected themselves. Two exceptions for a female with a X-linked recessive abnormality to have clinical symptoms: one is a manifesting carrier and the other is X-inactivation. A manifesting carrier usually has no noticeable problems at birth; symptoms show up later in life. In X-inactivation, the female (who would otherwise be a carrier, without any symptoms), actually presents with full-blown X-linked MTM. Thus, she congenitally presents (is born with) MTM.

Thus, although" MTM1" mutations most commonly cause problems in boys, these mutations can also cause clinical myopathy in girls, for the reasons noted above. Girls with myopathy and a muscle biopsy showing a centronuclear pattern should be tested for "MTM1" mutations.

Many clinicians and researchers use the abbreviations XL-MTM, XLMTM or X-MTM to emphasize that the genetic abnormality for myotubular myopathy (MTM) is X-linked (XL), having been identified as occurring on the X chromosome. The specific gene on the X chromosome is referred to as MTM-1. In theory, some cases of CNM may be caused by an abnormality on the X chromosome, but located at a different site from the gene "MTM1", but currently "MTM1" is the only X-linked genetic mutation site identified for myotubular or centronuclear myopathy. Clinical suspicion for X-linked inheritance would be a disease affecting multiple boys (but no girls) and a pedigree chart showing inheritance only through the maternal (mother’s) side of each generation.

There are rarely any specific tests for the congenital myopathies except for muscle biopsy. Tests can be run to check creatine kinase in the blood, which is often normal or mildly elevated in congenital myopathies. Electromyography can be run to check the electrical activity of the muscle. Diagnosis heavily relies on muscle pathology, where a muscle biopsy is visualised on the cellular level. Diagnosis usually relies on this method, as creatine kinase levels and electromyography can be unreliable and non-specific. Since congenital myopathies are genetic, there have been advancements in prenatal screenings.

On examination of muscle biopsy material, the nuclear material is located predominantly in the center of the muscle cells, and is described as having any "myotubular" or "centronuclear" appearance. In terms of describing the muscle biopsy itself, "myotubular" or "centronuclear” are almost synonymous, and both terms point to the similar cellular-appearance among MTM and CNM. Thus, pathologists and treating physicians use those terms almost interchangeably, although researchers and clinicians are increasingly distinguishing between those phrases.

In general, a clinical myopathy and a muscle biopsy showing a centronuclear (nucleus in the center of the muscle cell) appearance would indicate a centronuclear myopathy (CNM). The most commonly diagnosed CNM is myotubular myopathy (MTM). However, muscle biopsy analysis alone cannot reliably distinguish myotubular myopathy from other forms of centronuclear myopathies, and thus genetic testing is required.

Diagnostic workup is often coordinated by a treating neurologist. In the United States, care is often coordinated through clinics affiliated with the Muscular Dystrophy Association.

The recurrence of DOOR in siblings and the finding of DOOR syndrome in a few families with consanguinity suggest that the condition is an autosomal recessive genetic condition. Mutations in TBC1D24 have been identified in 9 families.

The diagnosis of AOS is a clinical diagnosis based on the specific features described above. A system of major and minor criteria was proposed.

The combination of two major criteria would be sufficient for the diagnosis of AOS, while a combination of one major and one minor feature would be suggestive of AOS. Genetic testing can be performed to test for the presence of mutation in one of the known genes, but these so far only account for an estimated 50% of patients with AOS. A definitive diagnosis may therefore not be achieved in all cases.

The disorder is characterized by absence or underdevelopment of the cerebellar vermis and a malformed brain stem (molar tooth sign), both of which can be visualized on a MRI scan. Together with this sign, the diagnosis is based on the physical symptoms and genetic testing for mutations. If the gene mutations have been identified in a family member, prenatal or carrier diagnosis can be pursued.

Joubert Syndrome is known to affect 1 in 80,000-100,000 newborns. Due to the variety of genes this disorder is affected by, it is likely to be under-diagnosed. It is commonly found in Ashkenazi Jewish, French-Canadians, and Hutterite ethnic populations. Most cases of Joubert syndrome are autosomal recessive - in these cases, both parents are either carriers or affected. Rarely, Joubert syndrome is inherited in an X-linked recessive pattern. In these cases, males are more commonly affected because affected males must have one X chromosome mutated, while affected females must have mutated genes on both X chromosomes.

Sandhoff disease is a rare, autosomal recessive metabolic disorder that causes progressive destruction of nerve cells in the brain and spinal cord. The disease results from mutations on chromosome 5 in the HEXB gene, critical for the lysosomal enzymes beta-N-acetylhexosaminidase A and B. Sandhoff Disease is clinically indistinguishable from Tay-Sachs Disease. The most common form, infantile Sandhoff disease, is usually fatal by early childhood.

A 2007 study followed 112 individuals for a mean of 12 years (mean age 25.3, range 12–71). No patient died during follow-up, but several required medical interventions. The mean final heights were 167 and 153 cm for men and women, respectively, which is approximately 2 standard deviations below normal.

The most useful information for accurate diagnosis is the symptoms and weakness pattern. If the quadriceps are spared but the hamstrings and iliopsoas are severely affected in a person between ages of 20 - 40, it is very likely HIBM will be at the top of the differential diagnosis. The doctor may order any or all of the following tests to ascertain if a person has IBM2:

- Blood test for serum Creatine Kinase (CK or CPK);

- Nerve Conduction Study (NCS) / Electomyography (EMG);

- Muscle Biopsy;

- Magnetic Resonance Imaging (MRI) or Computer Tomography (CT) Scan to determine true sparing of quadriceps;

- Blood Test or Buccal swab for genetic testing;

The conditions included under the term "congenital myopathy" can vary. One source includes nemaline myopathy, myotubular myopathy, central core myopathy, congenital fiber type disproportion, and multicore myopathy. The term can also be used more broadly, to describe conditions present from birth.