Many people with Crohn's disease have symptoms for years before the diagnosis. The usual onset is between 15 and 30 years of age, but can occur at any age. Because of the 'patchy' nature of the gastrointestinal disease and the depth of tissue involvement, initial symptoms can be more subtle than those of ulcerative colitis. People with Crohn's disease experience chronic recurring periods of flare-ups and remission.

Abdominal pain may be the initial symptom of Crohn's disease usually in the lower right area. It is often accompanied by diarrhea, especially in those who have had surgery. The diarrhea may or may not be bloody. The nature of the diarrhea in Crohn's disease depends on the part of the small intestine or colon involved. Ileitis typically results in large-volume, watery feces. Colitis may result in a smaller volume of feces of higher frequency. Fecal consistency may range from solid to watery. In severe cases, an individual may have more than 20 bowel movements per day and may need to awaken at night to defecate. Visible bleeding in the feces is less common in Crohn's disease than in ulcerative colitis, but may be seen in the setting of Crohn's colitis. Bloody bowel movements typically come and go, and may be bright or dark red in color. In the setting of severe Crohn's colitis, bleeding may be copious. Flatulence and bloating may also add to the intestinal discomfort.

Symptoms caused by intestinal stenosis are also common in Crohn's disease. Abdominal pain is often most severe in areas of the bowel with stenoses. Persistent vomiting and nausea may indicate stenosis from small bowel obstruction or disease involving the stomach, pylorus, or duodenum. Although the association is greater in the context of ulcerative colitis, Crohn's disease may also be associated with primary sclerosing cholangitis, a type of inflammation of the bile ducts.

Perianal discomfort may also be prominent in Crohn's disease. Itchiness or pain around the anus may be suggestive of inflammation, fistulization or abscess around the anal area or anal fissure. Perianal skin tags are also common in Crohn's disease and may appear with or without the presence of colorectal polyps. Fecal incontinence may accompany perianal Crohn's disease. At the opposite end of the gastrointestinal tract, the mouth may be affected by recurrent sores (aphthous ulcers). Rarely, the esophagus, and stomach may be involved in Crohn's disease. These can cause symptoms including difficulty swallowing (dysphagia), upper abdominal pain, and vomiting.

Crohn's disease, like many other chronic, inflammatory diseases, can cause a variety of systemic symptoms. Among children, growth failure is common. Many children are first diagnosed with Crohn's disease based on inability to maintain growth. As it may manifest at the time of the growth spurt in puberty, up to 30% of children with Crohn's disease may have retardation of growth. Fever may also be present, though fevers greater than 38.5 °C (101.3 °F) are uncommon unless there is a complication such as an abscess. Among older individuals, Crohn's disease may manifest as weight loss, usually related to decreased food intake, since individuals with intestinal symptoms from Crohn's disease often feel better when they do not eat and might lose their appetite. People with extensive small intestine disease may also have malabsorption of carbohydrates or lipids, which can further exacerbate weight loss.

According to recent studies, calcifications of channels seen in dementia can also occur in specific brain areas such as the visual complex in the occipital lobe. Such calcium channel blockages can cause visual problems or partial field hallucinations (Paroxysmal visual manifestations). Other papers show a link between migraine, visual aura and cerebral calcifications. Disturbances may be followed by

convulsions and associated with gastrointestinal phenomena.

Ten (of 75) young patients had neurologic findings such as febrile seizures, single generalized seizures, mild ataxia, and muscular hypotonia with retarded motor development, but magnetic resonance imaging detected unilateral and bilateral T2-hyperintensive white-matter lesions in 15 patients (20%)

Microvillus inclusion disease, also known as Davidson's disease, congenital microvillus atrophy and, less specifically, microvillus atrophy (note: microvillus is often misspelled as microvillous), is a rare genetic disorder of the small intestine that is inherited in an autosomal recessive pattern.

It is characterized by chronic, intractable diarrhea in new-born infants, starting in the first few days of life.

This results in metabolic acidosis and severe dehydration. Pregnancy and birth are usually normal.

LRBA deficiency presents as a syndrome of autoimmunity, lymphoproliferation, and humoral immune deficiency. Predominant clinical problems include idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), and an autoimmune enteropathy. Before the discovery of these gene mutations, patients were diagnosed with common variable immune deficiency (CVID), which is characterized by low antibody levels and recurrent infections. Infections mostly affect the respiratory tract, as many patients suffer from chronic lung disease, pneumonias, and bronchiectasis. Lymphocytic interstitial lung disease (ILD) is also observed, which complicates breathing and leads to impairment of lung function and mortality. Infections can also occur at other sites, such as the eyes, skin and gastrointestinal tract. Many patients suffer from chronic diarrhea and inflammatory bowel disease. Other clinical features can include hepatosplenomegaly, reoccurring warts, growth retardation, allergic dermatitis, and arthritis. Notably, LRBA deficiency has also been associated with type 1 diabetes mellitus. There is significant clinical phenotypic overlap with disease caused by CTLA4 haploinsufficiency. Since LRBA loss results in a loss of CTLA4 protein, the immune dysregulation syndrome of LRBA deficient patients can be attributed to the secondary loss of CTLA4. Because the predominant features of the disease include autoantibody-mediated disease (AIHA, ITP), Treg defects (resembling those found in CTLA4 haploinsufficient patients), autoimmune infiltration (of non-lymphoid organs, also resembling that found in CTLA4 haploinsufficient patients), and enteropathy, the disease has been termed LATAIE for LRBA deficiency with autoantibodies, Treg defects, autoimmune infiltration, and enteropathy.

Diverticulitis typically presents with left lower quadrant abdominal pain of sudden onset. There may also be fever, nausea, diarrhea or constipation, and blood in the stool.

Blau Syndrome is an autosomal dominant genetic inflammatory disorder which affects the skin, eyes, and joints. It is caused by a mutation in the NOD2 (CARD15) gene. Symptoms usually begin before the age of 4, and the disease manifests as early onset cutaneous sarcoidosis, granulomatous arthritis, and uveitis.

In complicated diverticulitis, an inflamed diverticulum can rupture, allowing bacteria to subsequently infect externally from the colon. If the infection spreads to the lining of the abdominal cavity (the peritoneum), peritonitis results. Sometimes, inflamed diverticula can cause narrowing of the bowel, leading to an obstruction. In some cases, the affected part of the colon adheres to the bladder or other organs in the pelvic cavity, causing a , or creating an abnormal connection between an organ and adjacent structure or other organ (in the case of diverticulitis, the colon and an adjacent organ).

Related pathologies may include:

- Bowel obstruction

- Peritonitis

- Abscess

- Bleeding

- Strictures

The risks associated with this syndrome include a strong tendency of developing cancer in a number of parts of the body. While the hamartomatous polyps themselves only have a small malignant potential (<3% - OHCM), patients with the syndrome have an increased risk of developing carcinomas of the pancreas, liver, lungs, breast, ovaries, uterus, testicles and other organs.

The average age of first diagnosis is 23, but the lesions can be identified at birth by an astute pediatrician or family physician. Prior to puberty, the mucocutaneous lesions can be found on the palms and soles. Often the first presentation is a bowel obstruction from an intussusception which is a common cause of mortality; an intussusception is a telescoping of one loop of bowel into another segment.

Underlying causes include gastric ulcers, duodenal ulcers, appendicitis, gastrointestinal cancer, diverticulitis, inflammatory bowel disease, superior mesenteric artery syndrome, trauma and ascariasis. Typhoid fever, non-steroidal anti-inflammatory drugs, ingestion of corrosives may also be responsible.

LRBA deficiency is a rare genetic disorder of the immune system. This disorder is caused by a mutation in the gene "LRBA". LRBA stands for “Lipopolysaccharide (LPS)-responsive vesicle trafficking, beach- and anchor-containing” gene. This condition is characterized by autoimmunity, lymphoproliferation, and immune deficiency. It was first described by Gabriela Lopez-Herrera from University College London in 2012. Investigators in the laboratory of Dr. Michael Lenardo at National Institute of Allergy and Infectious Diseases, the National Institutes of Health and Dr. Michael Jordan at Cincinnati Children’s Hospital Medical Center later described this condition and therapy in 2015.

Signs and symptoms may include a sudden pain in the epigastrium to the right of the midline indicating the perforation of a duodenal ulcer. In a gastric ulcer perforation creates a history of burning pain in epigastrium, with flatulence and dyspepsia.

In intestinal perforation, pain starts from the site of perforation and spreads across the abdomen.

Gastrointestinal perforation results in severe abdominal pain intensified by movement, nausea, vomiting and hematemesis. Later symptoms include fever and or chills. In any case, the abdomen becomes rigid with tenderness and rebound tenderness. After some time the abdomen becomes silent and heart sounds can be heard all over. Patient stops passing flatus and motion, abdomen is distended.

The symptoms of esophageal rupture may include sudden onset of chest pain.

Peutz–Jeghers syndrome (often abbreviated PJS) is an autosomal dominant genetic disorder characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa (melanosis). This syndrome can be classed as one of various hereditary intestinal polyposis syndromes and one of various hamartomatous polyposis syndromes. It has an incidence of approximately 1 in 25,000 to 300,000 births.

Berdon syndrome, also called Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIH syndrome), is an autosomal recessive fatal genetic disorder affecting newborns. In a 2011 study of 227 children with the syndrome, "the oldest survivor [was] 24 years old." The Ann Arbor News reported a five year old survivor at the end of 2015.

It is more prevalent in females, 7 females to 3 males, and is characterized by constipation and urinary retention, microcolon, giant bladder (megacystis), intestinal hypoperistalis, hydronephrosis, and dilated small bowel. The pathological findings consist of an abundance of ganglion cells in both dilated and narrow areas of the intestine. It is a familial disturbance of unknown cause.

Walter Berdon "et al." in 1976 first described the condition in five female infants, two of whom were sisters. All had marked dilatation of the bladder and some had hydronephrosis and the external appearance of prune belly. The infants also had microcolon and dilated small intestines.

The initial description of AGS suggested that the disease was always severe, and was associated with unremitting neurological decline, resulting in death in childhood. As more cases have been identified, it has become apparent that this is not necessarily the case, with many patients now considered to demonstrate an apparently stable clinical picture, alive in their 4th decade. Moreover, rare individuals with pathogenic mutations in the AGS-related genes can be minimally affected (perhaps only with chilblains) and are in mainstream education, and even affected siblings within a family can show marked differences in severity.

In about ten percent of cases, AGS presents at or soon after birth (i.e. in the neonatal period). This presentation of the disease is characterized by microcephaly, neonatal seizures, poor feeding, jitteriness, cerebral calcifications (accumulation of calcium deposits in the brain), white matter abnormalities, and cerebral atrophy; thus indicating that the disease process became active before birth i.e. "in utero". These infants can have hepatosplenomegaly and thrombocytopaenia, very much like cases of transplacental viral infection. About one third of such early presenting cases, most frequently in association with mutations in "TREX1", die in early childhood.

Otherwise the majority of AGS cases present in early infancy, sometimes after an apparently normal period of development. During the first few months after birth, these children develop features of an encephalopathy with irritability, persistent crying, feeding difficulties, an intermittent fever (without obvious infection), and abnormal neurology with disturbed tone, dystonia, an exaggerated startle response, and sometimes seizures.

Glaucoma can be present at birth, or develop later. Many children retain apparently normal vision, although a significant number are cortically blind. Hearing is almost invariably normal. Over time, up to 40% of patients develop so-called chilblain lesions, most typically on the toes and fingers and occasionally also involving the ears. They are usually worse in the winter.

An enterocutaneous fistula (ECF) is an abnormal communication between the small or large bowel and the skin that allows the contents of the stomach or intestines to leak through an opening in the skin.

From early adolescence, patients with this condition gradually (and much of the time 'silently') develop hundreds to thousands of colorectal polyps (and sometimes polyps elsewhere)—small abnormalities at the surface of the intestinal tract, especially in the large intestine including the colon or rectum. These may bleed, leading to blood in the stool. If the blood is not visible, it is still possible for the patient to develop anemia due to gradually developing iron deficiency. If malignancy develops, this may present with weight loss, altered bowel habit, or even metastasis to the liver or elsewhere. FAP can also develop 'silently' in some individuals, giving few or no signs until it has developed into advanced colorectal cancer.

Because familial polyposis develops very gradually over years, and can also manifest in an 'attenuated' form even more gradually, polyps resulting from FAP can lead to cancer developing at any point from adolescence to old age.

Depending on the nature of the defect in the APC gene, and whether it is the full or attenuated form, familial polyposis may manifest as polyps in colon or in the duodenal tract, or in any combination of these. Therefore, an absence of polyps in, for example, the rectum, may not of itself be sufficient to confirm absence of polyps. It may be necessary to consider and visually examine other possible parts of the intestinal tract. Colonoscopy is preferred over sigmoidoscopy for this, as it provides better observation of the common right-side location of polyps.

The genetic determinant in familial polyposis may also predispose carriers to other malignancies, e.g., of the duodenum and stomach (particularly ampullary adenocarcinoma). Other signs that may point to FAP are pigmented lesions of the retina ("CHRPE—congenital hypertrophy of the retinal pigment epithelium"), jaw cysts, sebaceous cysts, and osteomata (benign bone tumors). The combination of polyposis, osteomas, fibromas and sebaceous cysts is termed "Gardner's syndrome" (with or without abnormal scarring).

Regardless of cause, volvulus causes symptoms by two mechanisms:

- Bowel obstruction manifested as abdominal distension and bilious vomiting.

- Ischemia (loss of blood flow) to the affected portion of intestine.

Depending on the location of the volvulus, symptoms may vary. For example, in patients with a cecal volvulus, the predominant symptoms may be those of a small bowel obstruction (nausea, vomiting and lack of stool or flatus), because the obstructing point is close to the ileocecal valve and small intestine. In patients with a sigmoid volvulus, although abdominal pain may be present, symptoms of constipation may be more prominent.

Volvulus causes severe pain and progressive injury to the intestinal wall, with accumulation of gas and fluid in the portion of the bowel obstructed. Ultimately, this can result in necrosis of the affected intestinal wall, acidosis, and death. This is known as a closed loop obstruction because there exists an isolated ("closed") loop of bowel. Acute volvulus often requires immediate surgical intervention to untwist the affected segment of bowel and possibly resect any unsalvageable portion.

Volvulus occurs most frequently in middle-aged and elderly men. Volvulus can also arise as a rare complication in persons with redundant colon, a normal anatomic variation resulting in extra colonic loops.

Sigmoid volvulus is the most-common form of volvulus of the gastrointestinal tract. and is responsible for 8% of all intestinal obstructions. Sigmoid volvulus is particularly common in elderly persons and constipated patients. Patients experience abdominal pain, distension, and absolute constipation.

Cecal volvulus is slightly less common than sigmoid volvulus and is associated with symptoms of abdominal pain and small bowel obstruction.

Volvulus can also occur in patients with Duchenne muscular dystrophy due to the smooth muscle dysfunction.

Muir–Torre syndrome (MTS) is a rare hereditary, autosomal dominant cancer syndrome that is thought to be a subtype of HNPCC. Individuals are prone to develop cancers of the colon, genitourinary tract, and skin lesions, such as keratoacanthomas and sebaceous tumors. The genes affected are MLH1, MSH2, and more recently, MSH6, and are involved in DNA mismatch repair.

Often symptoms will arise that indicate the body is not absorbing or making the lipoproteins that it needs. These symptoms usually appear "en masse", meaning that they happen all together, all the time. These symptoms come as follows:

- Failure to thrive/Failure to grow in infancy

- Steatorrhea/Fatty, pale stools

- Frothy stools

- Foul smelling stools

- Protruding abdomen

- Intellectual disability/developmental delay

- Developmental coordination disorder, evident by age ten

- Muscle weakness

- Slurred speech

- Scoliosis (curvature of the spine)

- Progressive decreased vision

- Balance and coordination problems

Aicardi–Goutières syndrome (AGS), which is completely distinct from the similarly named Aicardi syndrome, is a rare, usually early onset childhood, inflammatory disorder most typically affecting the brain and the skin (neurodevelopmental disorder). The majority of affected individuals experience significant intellectual and physical problems, although this is not always the case. The clinical features of AGS can mimic those of "in utero" acquired infection, and some characteristics of the condition also overlap with the autoimmune disease systemic lupus erythematosus (SLE). Following an original description of eight cases in 1984, the condition was first referred to as 'Aicardi–Goutières syndrome' (AGS) in 1992, and the first international meeting on AGS was held in Pavia, Italy, in 2001.

AGS can occur due to mutations in any one of a number of different genes, of which seven have been identified to date, namely: TREX1, RNASEH2A, RNASEH2B, RNASEH2C (which together encode the Ribonuclease H2 enzyme complex), SAMHD1, ADAR1, and IFIH1 (coding for MDA5). This neurological disease occurs in all populations worldwide, although it is almost certainly under-diagnosed. To date (2014) at least 400 cases of AGS are known.

Common symptoms of the disease are weakness and atrophy in the distal muscles of the lower limbs which progresses to the hands and arms, then to the trunk, neck and face. Respiratory impairment often follows.

Onset : Early childhood

Progression: Chronic progressive

Clinical: Cerebellar ataxia plus syndrome / Optic Atrophy Plus Syndrome

Ocular: Optic atrophy, nystagmus, scotoma, and bilateral retrobulbar neuritis.

Other: Mental retardation, myoclonic epilepsy, spasticity, and posterior column sensory loss. Tremor in some cases.

Musculoskeletal

Contractures, lower limbs, Achilles tendon contractures, Hamstring contractures, Adductor longus contractures

Systemic

Hypogonadotrophic hypogonadism.