A woman starts failing after a family vacation; another woman, who has suffered from stomach pains for years, has problems with swelling during menstruation.

Jessica is stricken with fevers and crippling migraines, and after Jake starts a military training program he finds hundreds of painful, fatty lumps appearing on his body.

Carole, a 65-year-old woman, has a hard time walking in a straight line; Sonya and Sherwood are delighted with their second daughter, but they begin to worry when the baby does not stop crying. When a particularly unusual symptom emerges, followed by uncontrollable seizures, it is discovered that the infant is affected by maple syrup urine disease.

Diane finds two small, red bumps on her foot; within hours her foot is swollen and appears black and blue; despite undergoing tests, the medical team has no diagnosis.

Nicole is a teenager who feels excruciating pain in her jaw and her face starts to sink, with her affliction later found to be the result of Parry-Romberg syndrome. Kevin thinks he has food poisoning, but he starts to lose motor coordination.

A couple fear for their child when they discover that he does not cry when he is in pain; a woman in her thirties suffers inexplicable seizures.

For years, Mary has had a problem with constant belching; now having difficulty breathing, she is seen by gastroenterologist Dr Chey, who discovers something he has never seen before and diagnoses her with Congenital diaphragmatic hernia. Pam was an excellent ER nurse who seemed to have a good handle on her health, until she was struck with headaches, unequal pupils, and facial numbness; When cardiologist Dr Yadav saw her angiogram, he diagnosed her with Fibromuscular dysplasia

A young mother begins to have panic attacks and has a seizure; she experiences episodes of paranoia and delusions after being released from the hospital, which later escalate to outbreaks of intense violence after she is admitted once again. The cause is later found to be a teratoma and the body's attempts to get rid of it with an immune response, inadvertently targeting the brain in the form of Anti-NMDA receptor encephalitis. A truck driver and father of two had been caught off guard by mysterious pains in his feet. Later, he was experiencing temperature changes and the pain increased to the point where he had to quit his job. All hope was lost until a vascular specialist diagnosed him with Buerger’s disease on account of his heavy smoking.

Over the first several years of their life, a young girl experiences bouts of debilitating pain and degradation to her bones caused by lymphangiomatosis.

A woman experiences numerous unusual symptoms as a result of being infected by the bacteria Serratia marcescens, including an incident where her breast milk turns pink after being dyed with a chemical produced by the bacteria. An infant begins experiencing intense pain in their hip.

A woman experiences strange symptoms after breast reduction surgery; though the symptoms are initially attributed to the surgery, she is eventually diagnosed with inflammatory breast cancer. A baby has severe developmental delays, difficulty eating, and jerky movements; her unusually happy demeanor eventually leads to a diagnosis of Angelman syndrome.

Rachele Lacount and Mike West are delighted that their baby has started to walk and talk, but suddenly they realize that something is wrong with his right eye. Since middle school, Cherryl Marshall struggled with taming her obscene body odor.

An 18-month-old baby suddenly starts screaming one afternoon in the pool, and begins exhibiting extremely painful symptoms when exposed to sunlight, with porphyria later found to be the culprit. A mother of two children begins to suffer a series of very debilitating headaches.

A young student begins to suffer from paralyzing pain in his back. A couple adopts a girl and they find a huge and swollen lump on her shoulder. Initially suspected to be severe neurofibromatosis, the efforts of doctors to relieve the child's condition by conducting an amputation of the affected arm only makes things worse when bone begins overrunning the site of the amputation, revealing her condition to be the lethal and progressive disease fibrodysplasia ossificans progressiva.

Doctors are baffled by a woman's mysterious respiratory problem. Featuring Cushing's syndrome, gout, carcinoid cancer.

A college student's body is covered in blisters and her colleagues fear it will be contagious; a nurse has paralyzing back spasms and may lose her job.

June has a biopsy and, when a mark appears on the site, she has surgery, leaving her with a growing open wound. Her doctor diagnoses her with a flesh eating virus. Can June's life be saved?

After moving houses, and months of strange behavior, 12-year-old Sammy stops walking and only hops; the doctors are the only hope to discover the cause of his bizarre symptoms. He is eventually diagnosed with PANDAS, a condition in which antibodies mistake his brain for Streptococcus bacteria.

A baby develops a mysterious set of symptoms, including a bulging forehead and eye color changes. A teen suffers severe hand pain during swim practice.

Walt has always been in good health until one day he suddenly faints; when he arrives at hospital, his blood pressure is very low and he has gained 100 lb (45 kg) of weight in water. It is eventually discovered that he is suffering from systemic capillary leak syndrome.

After blisters appear all over the body of young Julie McCawley, she appears to have Stevens-Johnson syndrome; Conor Heybach's weight gain and uncontrollable appetite is a mystery until a doctor discovers he has Prader-Willi syndrome.

After suffering a series of debilitating incidents believed to be the result of Crohn's disease, Karen, an albino, has to have most of her colon removed. Several decades later, at the age of 38, she receives a phone call from someone who suggests she is suffering from a rare and fatal disease, Hermansky-Pudlak syndrome, which is also the cause of her albinism.

A man tries to ease his wife's sinus pains, while a woman faces her own mortality when she experiences a series of debilitating symptoms.

A doctor makes an unexpected discovery when he operates on a young woman; doctors try to reach a diagnosis when a marathon runner experiences mysterious fatigue.

An aspiring actress awakens to an excruciating pain on the right side of her face; Bill experiences nausea and strange tingling in his legs; doctor visits and MRI tests show how these two different cases reveal paralysis.

A woman has shortness of breath, chest and joint pain, extreme fatigue, and a cough; strange symptoms appear in an energetic kindergartener.

A baby boy has bouts of vomiting and diarrhea from the day of his birth; a young woman experiences blackouts after she hits puberty.

A young college student named Mary Ann Piazza is misdiagnosed with pneumonia, but her cough keeps worsening accompanied with extreme fatigue.