The severity of symptoms of idic(15) vary greatly between individuals. Individuals with idic(15) usually have delays in language development and motor skills such as walking or sitting up. Other traits may include low muscle tone (hypotonia), seizures (>50%), short stature, and intellectual disability. Distinctive facial features associated with idic(15), where present, are usually very subtle but may include epicanthal folds (skin folds at the inner corners of one or both eyes), broad forehead, a flattened nasal bridge, button nose, and a high arched palate (roof of the mouth). Many individuals with idic(15) display features of autism, such as problems with communication and social interactions, obsessional interests (often with interactive mechanisms like wheels, doors or switches), unpredictable sleep cycles (and a reduced need for sleep), and repetitive and stereotyped behaviors (e.g., lining up toys, playing with a toy in the same manner over and over again, hand flapping, rocking back and forth). A high pain threshold is often observed. If speech develops, it is often echolalic but some individuals do grasp some language. With a severely affected person there may be an inability to walk or talk.

Potocki–Lupski syndrome (PTLS), also known as dup(17)p11.2p11.2 syndrome, trisomy 17p11.2 or duplication 17p11.2 syndrome, is a contiguous gene syndrome involving the microduplication of band 11.2 on the short arm of human chromosome 17 (17p11.2). The duplication was first described as a case study in 1996. In 2000, the first study of the disease was released, and in 2007, enough patients had been gathered to complete a comprehensive study and give it a detailed clinical description. PTLS is named for two researchers involved in the latter phases, Drs. Lorraine Potocki and James R. Lupski of Baylor College of Medicine.

PTLS was the first predicted of a homologous recombination (microdeletion or microduplication) where both reciprocal recombinations result in a contiguous gene syndrome. Its reciprocal disease is Smith–Magenis syndrome (SMS), in which the chromosome portion duplicated in PTLS is deleted altogether.

Potocki–Lupski syndrome is considered a rare disease, predicted to appear in at least 1 in 20,000 humans.

Symptoms of the syndrome include intellectual disability, autism, and other disorders unrelated to the listed symptoms.

Isodicentric 15, also called idic(15), partial tetrasomy 15q, or inverted duplication 15 (inv dup 15), is a chromosome abnormality in which a child is born with extra genetic material from chromosome 15. People with idic(15) are typically born with 47 chromosomes in their body cells, instead of the normal 46. The extra chromosome is made up of a piece of chromosome 15 that has been duplicated end-to-end like a mirror image. It is the presence of this extra genetic material that is thought to account for the symptoms seen in some people with idic(15). Individuals with idic(15) have a total of four copies of this chromosome 15 region instead of the usual two copies (1 copy each on the maternal and paternal chromosomes).

The syndrome is also often referred to by the broader term "Chromosome 15q11.2-q13.1 Duplication Syndrome", shortened to Dup15q syndrome, a name that is supported and actively promoted by the US-based support organization Dup15q Alliance. Dup15q syndrome is a broader disease term, as it includes both idic(15) and interstitial 15q11.2-q13.1, another type of duplication that causes similar clinical traits.

The extra chromosome is occasionally found in the mosaic state, i.e. some of the cells carry the marker chromosome. However, mostly because of the marker's instability and tendency to be lost during cell division (mitosis), some cells are completely normal with 46 chromosomes. Occasionally, cells may have more than one idic(15), resulting in 48 or 49 chromosomes in all or some of their cells. A similar clinical picture albeit to a milder degree could be expected in individuals that have the extra chromosome 15 material as an interstitial duplication (when the extra piece of chromosome 15 is included "within" the long arm of one of the two copies of chromosome 15, rather than as a small extra 'marker' chromosome) - often abbreviated to int dup(15); the individual thus having 46 chromosomes.

Clinically, PTLS presents as a milder syndrome than SMS, with distinct characteristics, though PTLS can be mistaken for SMS. Both syndromes are characterized by multiple congenital abnormalities and mental retardation. A key feature which appears in 80% of cases is autism spectrum disorder. Other unique features of Potocki–Lupski syndrome include infantile hypotonia, sleep apnea, structural cardiovascular anomalies, cognitive deficits, abnormal social behaviors, learning disabilities, attention-deficit disorder, obsessive-compulsive behaviours, malocclusions, short stature and failure to thrive.

After noting that autism is commonly associated with PTLS, researchers at the Centro de Estudios Científicos and the Austral University of Chile genetically engineered a PTLS "model mouse" where the syntenic chromosome segment was duplicated, and examined the social behaviours of these mice versus those without the anomaly (the "wild-type"). One human autism-related symptom is abnormal social interaction. The researchers observed that the genetically-engineered mice of both sexes had a slight (statistically insignificant) impairment of their preference of a social target (i.e., a living, breathing mouse) over an inanimate one — the average human will prefer the social target — and preferred to explore newly introduced mice instead of familiar ones, unlike the typical human and mouse preference of a friend over a stranger, demonstrating a change in their liking of social novelty. They also found that male mice, in some scenarios, showed increased anxiety and than the control group. Anatomically, the engineered mice had a decreased brain-to-body mass ratio and an alteration in the expression of several genes in the hippocampus.

Symptoms typically begin in childhood and are progressive, often resulting in death by early adulthood. Symptoms of PKAN begin before middle childhood, and most often are noticed before ten years of age. Symptoms include:

- dystonia (repetitive uncontrollable muscle contractions that may cause jerking or twisting of certain muscle groups)

- dysphagia & dysarthria due to muscle groups involved in speech being involved

- rigidity/stiffness of limbs

- tremor

- writhing movements

- dementia

- spasticity

- weakness

- seizures (rare)

- toe walking

- retinitis pigmentosa, another degenerative disease that affects the individual’s retina, often causing alteration of retinal color and progressive deterioration of the retina at first causing night blindness and later resulting in a complete loss of vision.

25% of individuals experience an uncharacteristic form of PKAN that develops post-10 years of age and follows a slower, more gradual pace of deterioration than those pre-10 years of age. These individuals face significant speech deficits as well as psychiatric and behavioral disturbances.

Being a progressive, degenerative nerve illness, PKAN leads to early immobility and often death by early adulthood. Death occurs prematurely due to infections such as pneumonia, and the disease in itself is technically not life limiting.

Pantothenate kinase-associated neurodegeneration (PKAN), also known as neurodegeneration with brain iron accumulation 1 (NBIA1), also called Hallervorden–Spatz syndrome, is a degenerative disease of the brain that can lead to parkinsonism, dystonia, dementia, and ultimately death. Neurodegeneration in PKAN is accompanied by an excess of iron that progressively builds up in the brain.

Other conditions that can produce similar symptoms include: akathisia and nocturnal leg cramps.

Peripheral artery disease and arthritis can also cause leg pain but this usually gets worse with movement.

In 2003, a US National Institutes of Health (NIH) panel modified their criteria to include the following:

- An urge to move the limbs with or without sensations.

- Improvement with activity. Many patients find relief when moving and the relief continues while they are moving. In more severe RLS this relief of symptoms may not be complete or the symptoms may reappear when the movement ceases.

- Worsening at rest. Patients may describe being the most affected when sitting for a long period of time, such as when traveling in a car or airplane, attending a meeting, or watching a performance. An increased level of mental awareness may help reduce these symptoms.

- Worsening in the evening or night. Patients with mild or moderate RLS show a clear circadian rhythm to their symptoms, with an increase in sensory symptoms and restlessness in the evening and into the night.