People with CHS have light skin and silvery hair (albinism) and frequently complain of solar sensitivity and photophobia. Other signs and symptoms vary considerably, but frequent infections and neuropathy are common. The infections involve mucous membranes, skin, and the respiratory tract. Affected children are susceptible to infection by Gram-positive and gram-negative bacteria and fungi, with "Staphylococcus aureus" being the most common infection cause. Infections in CHS patients tend to be very serious and even life-threatening. Neuropathy often begins in the teenage years and becomes the most prominent problem. Few patients with this condition live to adulthood.

Most children with Chédiak–Higashi syndrome ultimately reach a stage known as the "accelerated phase", or the "lymphoma-like syndrome", in which defective white blood cells divide uncontrollably and invade many of the body's organs. The accelerated phase is associated with fever, episodes of abnormal bleeding, overwhelming infections, and organ failure. These medical problems are usually life-threatening in childhood.

Some of the symptoms and signs of IPEX syndrome are the following:

Chédiak–Higashi syndrome is a rare autosomal recessive disorder that arises from a mutation of a lysosomal trafficking regulator protein, which leads to a decrease in phagocytosis. The decrease in phagocytosis results in recurrent pyogenic infections, albinism and peripheral neuropathy. It occurs in humans, cattle, blue Persian cats, Australian blue rats, mice, mink, foxes, and the only known captive white orca.

This syndrome consists a number of typical features. These include

- Agenesis of the corpus callosum (80-99% patients)

- Hypopigmentation of the eyes and hair (80-99% patients)

- Cardiomyopathy (80-99% patients)

- Combined immunodeficiency (80-99% patients)

- Muscular hypotonia (80-99% patients)

- Abnormality of retinal pigmentation (80-99% patients)

- Recurrent chest infections (80-99% patients)

- Abnormal EEG (80-99% patients)

- Intellectual disability (80-99% patients)

- Cataracts (75%)

- Seizures (65%)

- Renal abnormalities (15%)

Infections of the gastrointestinal and urinary tracts are common. Swallowing and feeding difficulties early on may result in a failure to thrive. Optic nerve hypoplasia, nystagmus and photophobia may occur. Facial dysmorphism (cleft lip/palate and micrognathia) and syndactyly may be present. Sensorineural hearing loss may also be present.

Death in infancy is not uncommon and is usually due to cardiac complications or severe infections.

IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked) syndrome is a rare disease linked to the dysfunction of the transcription factor FOXP3, widely considered to be the master regulator of the regulatory T cell lineage. It leads to the dysfunction of regulatory T-cells and the subsequent autoimmunity. The disorder manifests with autoimmune enteropathy, psoriasiform or eczematous dermatitis, nail dystrophy, autoimmune endocrinopathies, and autoimmune skin conditions such as alopecia universalis and bullous pemphigoid.

Management for immunodysregulation polyendocrinopathy enteropathy X-linked syndrome has seen limited success in treating the syndrome by bone marrow transplantation.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and chloride channel in vertebrates that is encoded by the "CFTR" gene.

The CFTR gene codes for an ABC transporter-class ion channel protein that conducts chloride and thiocyanate ions across epithelial cell membranes. Mutations of the CFTR gene affecting chloride ion channel function lead to dysregulation of epithelial fluid transport in the lung, pancreas and other organs, resulting in cystic fibrosis. Complications include thickened mucus in the lungs with frequent respiratory infections, and pancreatic insufficiency giving rise to malnutrition and diabetes. These conditions lead to chronic disability and reduced life expectancy. In male patients, the progressive obstruction and destruction of the developing vas deferens (spermatic cord) and epididymis appear to result from abnormal intraluminal secretions, causing congenital absence of the vas deferens and male infertility.

Autoimmune polyendocrine syndrome type 1 symptoms and signs include the following:

- Hypoparathyroidism

- Hypogonadism

- Vitiligo

- Alopecia

- Malabsorption

- Anemia

- Cataract

- Adrenal hyperplasia

Autoimmune polyendocrine syndrome type 1 (APS-1), also known as autoimmune polyendocrinopathy-candidiasis–ectodermal dystrophy/dysplasia (APECED), autoimmune polyglandular syndrome type 1, Whitaker syndrome, or candidiasis-hypoparathyroidism–Addison's disease syndrome, is a subtype of autoimmune polyendocrine syndrome (autoimmune polyglandular syndrome) in which multiple endocrine glands dysfunction as a result of autoimmunity. It is a genetic disorder inherited in autosomal recessive fashion due to a defect in the "AIRE" gene (autoimmune regulator), which is located on chromosome 21 and normally confers immune tolerance.

Acquired C1 esterase inhibitor deficiency also known as "Acquired Angioedema" presents with symptoms indistinguishable from hereditary angioedema, but generally with onset after the fourth decade of life.

C4 levels are low and C3 levels are normal.

This includes Ataxia-telegiectasia, Chédiak-Higashi syndrome, DiGeorge syndrome, Griscelli syndrome and Marinesco-Sjogren syndrome.

Several X-linked syndromes include intellectual disability as part of the presentation. These include:

- Coffin–Lowry syndrome

- MASA syndrome

- MECP2 duplication syndrome

- X-linked alpha thalassemia mental retardation syndrome

- mental retardation and microcephaly with pontine and cerebellar hypoplasia

X-linked intellectual disability (previously known as X-linked mental retardation) refers to forms of intellectual disability which are specifically associated with X-linked recessive inheritance.

As with most X-linked disorders, males are more heavily affected than females. Females with one affected X chromosome and one normal X chromosome tend to have milder symptoms.

Unlike many other types of intellectual disability, the genetics of these conditions are relatively well understood. It has been estimated there are ~200 genes involved in this syndrome; of these ~100 have been identified.

X-linked intellectual disability accounts for ~16% of all cases of intellectual disability in males.

Lung disease results from clogging of the airways due to mucus build-up, decreased mucociliary clearance, and resulting inflammation. Inflammation and infection cause injury and structural changes to the lungs, leading to a variety of symptoms. In the early stages, incessant coughing, copious phlegm production, and decreased ability to exercise are common. Many of these symptoms occur when bacteria that normally inhabit the thick mucus grow out of control and cause pneumonia.

In later stages, changes in the architecture of the lung, such as pathology in the major airways (bronchiectasis), further exacerbate difficulties in breathing. Other signs include coughing up blood (hemoptysis), high blood pressure in the lung (pulmonary hypertension), heart failure, difficulties getting enough oxygen to the body (hypoxia), and respiratory failure requiring support with breathing masks, such as bilevel positive airway pressure machines or ventilators. "Staphylococcus aureus", "Haemophilus influenzae", and "Pseudomonas aeruginosa" are the three most common organisms causing lung infections in CF patients. In addition to typical bacterial infections, people with CF more commonly develop other types of lung disease. Among these is allergic bronchopulmonary aspergillosis, in which the body's response to the common fungus "Aspergillus fumigatus" causes worsening of breathing problems. Another is infection with "Mycobacterium avium" complex, a group of bacteria related to tuberculosis, which can cause lung damage and does not respond to common antibiotics.

Mucus in the paranasal sinuses is equally thick and may also cause blockage of the sinus passages, leading to infection. This may cause facial pain, fever, nasal drainage, and headaches. Individuals with CF may develop overgrowth of the nasal tissue (nasal polyps) due to inflammation from chronic sinus infections. Recurrent sinonasal polyps can occur in 10% to 25% of CF patients. These polyps can block the nasal passages and increase breathing difficulties.

Cardiorespiratory complications are the most common cause of death (about 80%) in patients at most CF centers in the United States.

The main signs and symptoms of cystic fibrosis are salty-tasting skin, poor growth, and poor weight gain despite normal food intake, accumulation of thick, sticky mucus, frequent chest infections, and coughing or shortness of breath. Males can be infertile due to congenital absence of the vas deferens. Symptoms often appear in infancy and childhood, such as bowel obstruction due to meconium ileus in newborn babies. As the children grow, they exercise to release mucus in the alveoli. Ciliated epithelial cells in the person have a mutated protein that leads to abnormally viscous mucus production. The poor growth in children typically presents as an inability to gain weight or height at the same rate as their peers, and is occasionally not diagnosed until investigation is initiated for poor growth. The causes of growth failure are multifactorial and include chronic lung infection, poor absorption of nutrients through the gastrointestinal tract, and increased metabolic demand due to chronic illness.

In rare cases, cystic fibrosis can manifest itself as a coagulation disorder. Vitamin K is normally absorbed from breast milk, formula, and later, solid foods. This absorption is impaired in some cystic fibrosis patients. Young children are especially sensitive to vitamin K malabsorptive disorders because only a very small amount of vitamin K crosses the placenta, leaving the child with very low reserves and limited ability to absorb vitamin K from dietary sources after birth. Because factors II, VII, IX, and X (clotting factors) are vitamin K–dependent, low levels of vitamin K can result in coagulation problems. Consequently, when a child presents with unexplained bruising, a coagulation evaluation may be warranted to determine whether an underlying disease is present.

Genitopatellar syndrome is a rare condition characterized by genital abnormalities, missing or underdeveloped kneecaps (patellae), intellectual disability, and abnormalities affecting other parts of the body.

Genitopatellar syndrome is also associated with delayed development and intellectual disability, which are often severe. Affected individuals may have an unusually small head (microcephaly) and structural brain abnormalities, including underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum).

Symptoms generally begin around puberty but can occur earlier. These individuals have recurrent swelling in the extremities, genitals, face, lips, larynx or GI tract. Some patients describe a sensation of fullness but not pain or itching in the affected area except for those with abdominal swellings who often experience acute abdominal pain. Others experience an intense amount of pain, described as radiating from the bone outward along with intense itching just beneath the skin and intense heat, regardless of the area targeted.

Instances of swelling around the throat or larynx can cause difficulties in breathing should the swelling obstruct airways. This has been known to cause a large number of fatalities in those afflicted with the disorder. Episodes that attack the gastrointestinal tract can cause a number of complications including dehydration from being unable to keep anything down (which, depending on length of the episode, can prove fatal). Symptoms from gI tract swelling including violent vomiting, intense pain from the midsection, dehydration, and intense exhaustion.

Some suffered of HAE suffer from 'wandering' attacks. These attacks will center around an extremity. For example: Should the sufferer's hand swell up, it will go through the normal swelling cycle before 'transferring' to either the connection limb (In this case wrist to forearm) or move to the opposite hand. Sufferers with this symptom may find their episodes last longer, and may find their triggers more difficult to track.

Acropectoral syndrome is an autosomal dominant skeletal dysplasia syndrome affecting the hands, feet, sternum, and lumbosacral spine. A recently proposed candidate gene for preaxial polydactyly is LMBR1, encoding a novel transmembrane receptor, which may be an upstream regulator of SHH. The LMBR1 gene is on human chromosome 7q36.

Genitopatellar syndrome is a rare disorder with characteristic craniofacial features, congenital flexion contractures of the lower limbs, absent or abnormal patellae, urogenital anomalies, and severe psychomotor retardation.

In 2012, it was shown that mutations in the gene KAT6B cause the syndrome.

Transaldolase deficiency is a disease characterised by abnormally low levels of the Transaldolase enzyme. It is a metabolic enzyme involved in the pentose phosphate pathway. It is caused by mutation in the transaldolase gene (TALDO1). It was first described by Verhoeven et al. in 2001.

Some individuals have preaxial polydactyly in the feet (unilateral in one, bilateral in 13), consisting of a small extra biphalangeal toe, in most cases with an associated rudimentary extra metatarsal, lying in a soft tissue web between the hallux and second toe. In some cases, this was accompanied by hypoplasia of the head of the first metatarsal and absence of both phalanges of the hallux.

NF-1 is a progressive and diverse condition, making the prognosis difficult to predict. The NF-1 gene mutations manifest the disorder differently even amongst people of the same family. This phenomenon is called variable expressivity. For example, some individuals have no symptoms, while others may have a manifestation that is rapidly more progressive and severe.

For many NF-1 patients, a primary concern is the disfigurement caused by cutaneous/dermal neurofibromas, pigmented lesions, and the occasional limb abnormalities. However, there are many more severe complications caused by NF-1, although most of them are quite rare. Many NF patients live perfectly normal and uninterrupted lives.

LCH provokes a non-specific inflammatory response, which includes fever, lethargy, and weight loss. Organ involvement can also cause more specific symptoms.

- Bone: The most-frequently seen symptom in both unifocal and multifocal disease is painful bone swelling. The skull is most frequently affected, followed by the long bones of the upper extremities and flat bones. Infiltration in hands and feet is unusual. Osteolytic lesions can lead to pathological fractures.

- Skin: Commonly seen are a rash which varies from scaly erythematous lesions to red papules pronounced in intertriginous areas. Up to 80% of LCH patients have extensive eruptions on the scalp.

- Bone marrow: Pancytopenia with superadded infection usually implies a poor prognosis. Anemia can be due to a number of factors and does not necessarily imply bone marrow infiltration.

- Lymph node: Enlargement of the liver in 20%, spleen in 30% and lymph nodes in 50% of Histiocytosis cases.

- Endocrine glands: Hypothalamic pituitary axis commonly involved. Diabetes insipidus is most common. Anterior pituitary hormone deficiency is usually permanent.

- Lungs: some patients are asymptomatic, diagnosed incidentally because of lung nodules on radiographs; others suffer from chronic cough and shortness of breath.

- Less frequently gastrointestinal tract, central nervous system, and oral cavity.

Musculoskeletal abnormalities affecting the skull include Sphenoid bone dysplasia, Congenital Hydrocephalus and associated neurologic impairment. These abnormalities are non-progressive and may be diagnosed in the fetus or at birth.

Disorders affecting the spine include:

- In NF-1, there can be a generalized abnormality of the soft tissues in the fetus, which is referred to as mesodermal dysplasia, resulting in maldevelopment of skeletal structures.

- Meningoceles and formation of cystic diverticula of the dura of the spine, unrelated to Spina bifida

- Radiographically, Dural ectasia can lead to scalloping of the posterior vertebral bodies and to the formation of cystic diverticula of the dura of the spine (termed meningoceles. This meningocele is not related to spina bifida).

- Focal scoliosis and/or kyphosis are the most common skeletal manifestation of NF-1, occurring in 20% of affected patients. Approximately 25% of patients will require corrective surgery.

Skeletal muscle weakness and motor control deficits

Deficits in motor function in NF-1 have been long recognised and have been historically attributed to nerve dysfunction. In recent years however, studies suggest NF-1 is associated with a primary problem in muscle function (myopathy).

Clinical findings in people with NF-1 include:

- Reduced skeletal muscle size

- Reduced exercise capacity

- Muscle weakness (The most recent study reports between 30–50% reduced upper and lower limb muscle strength in NF-1 children compare with matched controls ).

Studies in genetically modified mice have thus far confirmed that the NF1 gene is vital for normal muscle development and metabolism. Knockout of the NF1 gene in muscle results in deregulated lipid metabolism and muscle weakness.

It is interesting to note that NF-1 is a disease in the RASopathy family of diseases, which include Costello Syndrome, Noonan Syndrome, and Cardiofaciocutaneous syndrome. The RASopathies also present with skeletal muscle weakness. It is likely that impaired muscle function in these disorders is linked to altered Ras/MAPK signalling, however, the precise molecular mechanisms remain unknown.

Direct sequence analysis of genomic DNA from blood can be used to perform a mutation analysis for the TALDO1 gene responsible for the Transaldolase enzyme.

Seen mostly in children, multifocal unisystem LCH is characterized by fever, bone lesions and diffuse eruptions, usually on the scalp and in the ear canals. 50% of cases involve the pituitary stalk, leading to diabetes insipidus. The triad of diabetes insipidus, exopthalmos, and lytic bone lesions is known as the "Hand-Schüller-Christian triad". Peak onset is 2–10 years of age.