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Pathology - Job Syndrome
caused by a mutation on chromosome 7q21 in the STAT3 gene.
The pathophysiological understanding A family of transcription factors known as STAT3 proteins is involved in signaling and the synthesis of cytokines. Decreased IL-6 and IL-23 signaling impairs the ability of a subset of helper T cells (Th 17) to differentiate. These cells are essential for the production of cytokines (IL-17 and IL-22) that are required to destroy bacteria and fungus. Decreased production of IL-10 and IL-4, which control the release of pro-inflammatory cytokines, raises interferon-gamma or tumor necrosis factor levels, which can then raise IgE levels.
Pathology
presents with eczema, recurrent infections (such as pneumonia, sinusitis, and otitis), and non-inflamed, cold staphylococcal abscesses; patients may also have skeletal anomalies, such as coarse facial features, scoliosis, and retained primary teeth.
results from the lab: increased levels of lgE and eosinophilia.
Treatment: Antibiotics for both infection prevention and treatment.
Remarks A malfunction in the CD40 ligand on CD4 T helper cells causes the inability to class switch from lgM to other classes, which is the cause of hyper-IgM syndrome. Early in life, it exhibits severe pyogenic infections.
caused by a mutation on chromosome 7q21 in the STAT3 gene.
The pathophysiological understanding A family of transcription factors known as STAT3 proteins is involved in signaling and the synthesis of cytokines. Decreased IL-6 and IL-23 signaling impairs the ability of a subset of helper T cells (Th 17) to differentiate. These cells are essential for the production of cytokines (IL-17 and IL-22) that are required to destroy bacteria and fungus. Decreased production of IL-10 and IL-4, which control the release of pro-inflammatory cytokines, raises interferon-gamma or tumor necrosis factor levels, which can then raise IgE levels.
Pathology
presents with eczema, recurrent infections (such as pneumonia, sinusitis, and otitis), and non-inflamed, cold staphylococcal abscesses; patients may also have skeletal anomalies, such as coarse facial features, scoliosis, and retained primary teeth.
results from the lab: increased levels of lgE and eosinophilia.
Treatment: Antibiotics for both infection prevention and treatment.
Remarks A malfunction in the CD40 ligand on CD4 T helper cells causes the inability to class switch from lgM to other classes, which is the cause of hyper-IgM syndrome. Early in life, it exhibits severe pyogenic infections.
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Pathology - Langerhans Cell Histiocytosis
Caused by aberrant proliferation of dendritic tumor cells, which are in charge of presenting antigens to T and B cells and express HLA-DR and CD1a.
Pathology Gross: Lesions affect the skin, bones, lungs, and stomach, among other organ systems.
Under the microscope: eosinophils in lesions associated with eosinophilic granuloma; proliferation of neoplastic histiocytic cells resembling epidermal Langerhans cells; Birbeck granules, cytoplasmic aggregates shaped like tennis rackets, within neoplastic cells.
Skin involvement with a maculopapular erythematous rash, usually on the torso, scalp, or in the creases of the elbow or knee; endocrinologic abnormalities (including diabetes insipidus, hypothalamus deficiency, or delayed puberty); otitis media; involvement of the bones with lesions or fractures presenting in the skull or long bones; infiltrative pulmonary disease; lymphadenopathy; liver dysfunction.
Therapy: chemotherapy (cyclosporine, for example); bone marrow transplantation may be an option.
Caused by aberrant proliferation of dendritic tumor cells, which are in charge of presenting antigens to T and B cells and express HLA-DR and CD1a.
Pathology Gross: Lesions affect the skin, bones, lungs, and stomach, among other organ systems.
Under the microscope: eosinophils in lesions associated with eosinophilic granuloma; proliferation of neoplastic histiocytic cells resembling epidermal Langerhans cells; Birbeck granules, cytoplasmic aggregates shaped like tennis rackets, within neoplastic cells.
Skin involvement with a maculopapular erythematous rash, usually on the torso, scalp, or in the creases of the elbow or knee; endocrinologic abnormalities (including diabetes insipidus, hypothalamus deficiency, or delayed puberty); otitis media; involvement of the bones with lesions or fractures presenting in the skull or long bones; infiltrative pulmonary disease; lymphadenopathy; liver dysfunction.
Therapy: chemotherapy (cyclosporine, for example); bone marrow transplantation may be an option.
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Pathology - Amyloidosis
Primary: Linked to dyscrasias of the plasma cell.
Secondary: Develops as a side effect of underlying long-term inflammatory conditions (RA, IBD) or long-term infections (TB, osteomyelitis).
Primary: Monoclonal immunoglobulin light chains (AL protein) are deposited in the heart, gastrointestinal tract, muscles, brain, and kidneys, typically.
Secondary: The skin, GI tract, and kidneys are typically affected by the deposition of AA protein, which is produced from apolipoprotein precursors.
Histopathology: The amyloid protein exhibits apple-green birefringence when stained with Congo red.
Pathophysiology: Insoluble protein fibrils infiltrate tissues, resulting in impaired organ function.
The symptoms (such as nephrotic syndrome, renal failure, restrictive cardiomyopathy, arthritis, neuropathy, intestinal malabsorption, and respiratory failure) are associated with the malfunction of the implicated organ.
Management
First: prednisone and melphalan; organ transplant, then bone marrow transplant.
Secondary: Treating predisposed diseases aggressively.
Other conditions involving amyloid deposition include diabetes (islet amyloid polypeptide), Alzheimer's disease (amyloid beta protein), Portuguese type polyneuropathy (transthyretin), nephropathic hereditary amyloidosis (AA protein), medullary thyroid cancer (amyloid formed from calcitonin precursors), and dialysis amyloidosis (beta-microglobulin).
Primary: Linked to dyscrasias of the plasma cell.
Secondary: Develops as a side effect of underlying long-term inflammatory conditions (RA, IBD) or long-term infections (TB, osteomyelitis).
Primary: Monoclonal immunoglobulin light chains (AL protein) are deposited in the heart, gastrointestinal tract, muscles, brain, and kidneys, typically.
Secondary: The skin, GI tract, and kidneys are typically affected by the deposition of AA protein, which is produced from apolipoprotein precursors.
Histopathology: The amyloid protein exhibits apple-green birefringence when stained with Congo red.
Pathophysiology: Insoluble protein fibrils infiltrate tissues, resulting in impaired organ function.
The symptoms (such as nephrotic syndrome, renal failure, restrictive cardiomyopathy, arthritis, neuropathy, intestinal malabsorption, and respiratory failure) are associated with the malfunction of the implicated organ.
Management
First: prednisone and melphalan; organ transplant, then bone marrow transplant.
Secondary: Treating predisposed diseases aggressively.
Other conditions involving amyloid deposition include diabetes (islet amyloid polypeptide), Alzheimer's disease (amyloid beta protein), Portuguese type polyneuropathy (transthyretin), nephropathic hereditary amyloidosis (AA protein), medullary thyroid cancer (amyloid formed from calcitonin precursors), and dialysis amyloidosis (beta-microglobulin).
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Pathology - Down Syndrome
95% of cases are caused by trisomy 21 (typically due to meiotic nondisjunction). Trisomy 21 becomes more common as women age, resulting in 1 in 25 infants to moms over 45 having Down syndrome.
Four percent of instances are caused by Robertsonian translocation. Chr 21's long arm is translocated to a different chromosome, typically chromosomes 14 or 22.
Mosaicism, which makes up 1% of cases, is caused by chr 21's nondisjunction during mitosis during embryogenesis.
Features
Extremely delayed development; atresia of the duodenum and esophagus; palmar crease in one hand only; small hands with simian crease; distinct features of the face: flat face, epicanthal folds, wide-set eyes, and Brushfield spots (white spots around the iris).
Congenital heart problems include AV valve anomalies, VSDs, and ostium primum ASD caused by endocardial cushion deficiencies.
Difficulties
Middle-aged individuals with Down syndrome are more likely to experience acute leukemias, be more vulnerable to infections, and experience degenerative brain changes that resemble Alzheimer's disease.
Duodenal atresia and congenital cardiac abnormalities should be treated as needed.
Prognosis: Life expectancy is decreased, yet more than 80% of patients live past the age of thirty.
95% of cases are caused by trisomy 21 (typically due to meiotic nondisjunction). Trisomy 21 becomes more common as women age, resulting in 1 in 25 infants to moms over 45 having Down syndrome.
Four percent of instances are caused by Robertsonian translocation. Chr 21's long arm is translocated to a different chromosome, typically chromosomes 14 or 22.
Mosaicism, which makes up 1% of cases, is caused by chr 21's nondisjunction during mitosis during embryogenesis.
Features
Extremely delayed development; atresia of the duodenum and esophagus; palmar crease in one hand only; small hands with simian crease; distinct features of the face: flat face, epicanthal folds, wide-set eyes, and Brushfield spots (white spots around the iris).
Congenital heart problems include AV valve anomalies, VSDs, and ostium primum ASD caused by endocardial cushion deficiencies.
Difficulties
Middle-aged individuals with Down syndrome are more likely to experience acute leukemias, be more vulnerable to infections, and experience degenerative brain changes that resemble Alzheimer's disease.
Duodenal atresia and congenital cardiac abnormalities should be treated as needed.
Prognosis: Life expectancy is decreased, yet more than 80% of patients live past the age of thirty.
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Pathology- Patau Syndrome and the Edwards Syndrome
Etiology
Trisomy 18 is the primary cause of Edwards syndrome, typically resulting from meiotic nondisjunction. Maternal age increases the incidence. A few cases are due to mosaicism, which is the outcome of chromosome 18's nondisjunction during mitosis during embryogenesis.
Trisomy 13 is the primary cause of Patau syndrome, typically resulting from meiotic nondisjunction.
Maternal age increases the incidence. A small number of cases are due to mosaicism, which is brought on by translocation between chromosomes 13 and 14 or mitotic nondisjunction of chr 13 during embryogenesis.
Edwards syndrome is characterized by a severe developmental delay, feet that rock back and forth, broad occiput, low-set ears, micrognathia (small jaw), congenital heart and renal abnormalities, and overlapping third and fourth fingers.
Microcephaly and holoprosencephaly, cleft lip and palate, microphthalmia (small eyes), polydactyly, congenital cardiac and kidney abnormalities, umbilical hernia, and rocker-bottom feet are all symptoms of Patau syndrome.
The Patau and Edwards syndromes are fatal during the first year of life.
Etiology
Trisomy 18 is the primary cause of Edwards syndrome, typically resulting from meiotic nondisjunction. Maternal age increases the incidence. A few cases are due to mosaicism, which is the outcome of chromosome 18's nondisjunction during mitosis during embryogenesis.
Trisomy 13 is the primary cause of Patau syndrome, typically resulting from meiotic nondisjunction.
Maternal age increases the incidence. A small number of cases are due to mosaicism, which is brought on by translocation between chromosomes 13 and 14 or mitotic nondisjunction of chr 13 during embryogenesis.
Edwards syndrome is characterized by a severe developmental delay, feet that rock back and forth, broad occiput, low-set ears, micrognathia (small jaw), congenital heart and renal abnormalities, and overlapping third and fourth fingers.
Microcephaly and holoprosencephaly, cleft lip and palate, microphthalmia (small eyes), polydactyly, congenital cardiac and kidney abnormalities, umbilical hernia, and rocker-bottom feet are all symptoms of Patau syndrome.
The Patau and Edwards syndromes are fatal during the first year of life.
Patau Syndrome
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Pathology- Prader-Willi Syndrome and Angelman Syndrome
The same deletion on chr 15q is the cause of both disorders.
demonstrates the phenomenon known as imprinting, in which the same mutation, depending on whether the altered chromosome was of paternal or maternal origin, leads in distinct phenotypes.
Prader-Willi syndrome: hypogonadism, hypotonia, developmental delay, and an absence of a gene on a paternally derived chromosome. Obesity frequently results in diabetes.
"Happy puppet" with ataxic movement and inappropriate laughter, seizures, developmental delay, and a deletion on a chromosome derived from the mother characterize Angelman syndrome.
symptom management under constant observation.
The same deletion on chr 15q is the cause of both disorders.
demonstrates the phenomenon known as imprinting, in which the same mutation, depending on whether the altered chromosome was of paternal or maternal origin, leads in distinct phenotypes.
Prader-Willi syndrome: hypogonadism, hypotonia, developmental delay, and an absence of a gene on a paternally derived chromosome. Obesity frequently results in diabetes.
"Happy puppet" with ataxic movement and inappropriate laughter, seizures, developmental delay, and a deletion on a chromosome derived from the mother characterize Angelman syndrome.
symptom management under constant observation.
Prader Willi Syndrome
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Pathology - Systemic Sclerosis
Although the etiology is uncertain, anomalies in immune system activation have been proposed.
most frequently affects women in the 30 to 50 age range.
General pathology: The skin, heart, lungs, joints, GI tract (particularly the esophagus), and kidneys are the organs most frequently affected by fibrosis and collagen deposition.
Skin: Possible subcutaneous calcifications; eventual dermal fibrosis; perivascular lymphocytic infiltration with edema.
GI tract: loss of villi and microvilli in the small bowel; fibrosis and atrophy of the muscles.
Joints: Synovial tissue hypertrophy accompanied by synovium inflammation.
Kidneys: Vascular fibrinoid necrosis; intimal thickening with collagenous deposition in vessel walls.
Lungs: Vasospasm-induced pulmonary hypertension; interstitial fibrosis.
Heart: myocardial fibrosis and pericarditis.
gastroesophageal reflux disease, dysphagia, pulmonary fibrosis, pulmonary hypertension, Raynaud phenomenon, nephritic syndrome, arrhythmias, arthralgias with joint contractures, hypertension, and extensive skin thickening (scleroderma).
Positive ANA and anti-Scl-70 antibodies were found in the lab.
Systemic sclerosis has no FDA-approved treatments. Variable outcomes have been observed in small studies assessing the effects of D-penicillamine, rnycophenolate mofetil, cyclophosphamide, and bone marrow transplant.
The term "CREST syndrome" describes a form of systemic sclerosis that mostly affects the face and hands. It is typically associated with telangiectasia, esophageal dysmotility (dysphagia), calcinosis, Raynaud phenomenon, and sclerodactyly (hands that resemble claws). An anticentromere antibody test result of positive is frequently linked to CREST syndrome.
Although the etiology is uncertain, anomalies in immune system activation have been proposed.
most frequently affects women in the 30 to 50 age range.
General pathology: The skin, heart, lungs, joints, GI tract (particularly the esophagus), and kidneys are the organs most frequently affected by fibrosis and collagen deposition.
Skin: Possible subcutaneous calcifications; eventual dermal fibrosis; perivascular lymphocytic infiltration with edema.
GI tract: loss of villi and microvilli in the small bowel; fibrosis and atrophy of the muscles.
Joints: Synovial tissue hypertrophy accompanied by synovium inflammation.
Kidneys: Vascular fibrinoid necrosis; intimal thickening with collagenous deposition in vessel walls.
Lungs: Vasospasm-induced pulmonary hypertension; interstitial fibrosis.
Heart: myocardial fibrosis and pericarditis.
gastroesophageal reflux disease, dysphagia, pulmonary fibrosis, pulmonary hypertension, Raynaud phenomenon, nephritic syndrome, arrhythmias, arthralgias with joint contractures, hypertension, and extensive skin thickening (scleroderma).
Positive ANA and anti-Scl-70 antibodies were found in the lab.
Systemic sclerosis has no FDA-approved treatments. Variable outcomes have been observed in small studies assessing the effects of D-penicillamine, rnycophenolate mofetil, cyclophosphamide, and bone marrow transplant.
The term "CREST syndrome" describes a form of systemic sclerosis that mostly affects the face and hands. It is typically associated with telangiectasia, esophageal dysmotility (dysphagia), calcinosis, Raynaud phenomenon, and sclerodactyly (hands that resemble claws). An anticentromere antibody test result of positive is frequently linked to CREST syndrome.
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Pathology - Marfan Syndrome
Caused by a mutation in the fibrillin gene on chromosome 15; 20% of mutations are sporadic, while the majority are hereditary (autosomal dominant).
Pathophysiology: A faulty extracellular matrix results from a mutation in the fibrillin gene, a glycoprotein component of microfibrils.
Cardiovascular conditions include mitral valve prolapse (caused by the loss of connective tissue support for the valvular leaflet) and cystic medial necrosis of the aorta (which causes the aortic valve to dilate and weaken, increasing the risk of an intimal tear).
Eye: Lens displacement or bilateral subluxation.
Skeletal: Pigeon-breast deformity; spinal deformities (kyphosis, scoliosis).
Tall height with long extremities, scoliosis, ectopia lentis (dislocation of lenses), hyperextensible joints, long tapering digits (arachnodactyly), and aortic valve insufficiency as a result of aortic root dilatation.
One of the complications is a higher chance of developing a dissecting aortic aneurysm.
Management
An aortic root replacement if necessary, angiotensin receptor blockers, regular eye exams, and a spine brace if necessary are all recommended.
Caused by a mutation in the fibrillin gene on chromosome 15; 20% of mutations are sporadic, while the majority are hereditary (autosomal dominant).
Pathophysiology: A faulty extracellular matrix results from a mutation in the fibrillin gene, a glycoprotein component of microfibrils.
Cardiovascular conditions include mitral valve prolapse (caused by the loss of connective tissue support for the valvular leaflet) and cystic medial necrosis of the aorta (which causes the aortic valve to dilate and weaken, increasing the risk of an intimal tear).
Eye: Lens displacement or bilateral subluxation.
Skeletal: Pigeon-breast deformity; spinal deformities (kyphosis, scoliosis).
Tall height with long extremities, scoliosis, ectopia lentis (dislocation of lenses), hyperextensible joints, long tapering digits (arachnodactyly), and aortic valve insufficiency as a result of aortic root dilatation.
One of the complications is a higher chance of developing a dissecting aortic aneurysm.
Management
An aortic root replacement if necessary, angiotensin receptor blockers, regular eye exams, and a spine brace if necessary are all recommended.
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Pathology - Ehlers-Danlos Syndrome (EDS)
A condition that has ten distinct variations, all of which are linked to improper collagen synthesis. Autosomal dominant (types I–IV, VIIA–B, VIII), autosomal recessive (types VI, VIIC, X), and X-linked recessive (types V, IX) are the three different modes of inheritance.
Pathophysiology: When collagen is mutated, the structures it makes up become weaker. This can result in hyperextensible joints due to weak tendons, skeletal abnormalities due to aberrant bone development, and a weakened skin and vascular wall that makes an organ vulnerable to injury.
Skin: A disorganized, twisted mass of differently sized collagen strands.
Depending on the version, presentations change.
Thin, hyperextensible skin, easily bruised, hypermobile joints worsened by dislocation, weak muscles, atypical teeth, and prolapsed mitral valve are common symptoms.
Treatment: symptomatic treatment for osteoarthritis; vitamin C supplements (involved in collagen formation).
A condition that has ten distinct variations, all of which are linked to improper collagen synthesis. Autosomal dominant (types I–IV, VIIA–B, VIII), autosomal recessive (types VI, VIIC, X), and X-linked recessive (types V, IX) are the three different modes of inheritance.
Pathophysiology: When collagen is mutated, the structures it makes up become weaker. This can result in hyperextensible joints due to weak tendons, skeletal abnormalities due to aberrant bone development, and a weakened skin and vascular wall that makes an organ vulnerable to injury.
Skin: A disorganized, twisted mass of differently sized collagen strands.
Depending on the version, presentations change.
Thin, hyperextensible skin, easily bruised, hypermobile joints worsened by dislocation, weak muscles, atypical teeth, and prolapsed mitral valve are common symptoms.
Treatment: symptomatic treatment for osteoarthritis; vitamin C supplements (involved in collagen formation).
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Pathology - Albinism and Vitiligo
Albinism : Melanocytes are produced from neural crest ectoderm, hence albinism may be associated to faulty neural crest cell migration. Tyrosinase deficiency or a lack of tyrosine uptake into the melanocyte are the two main causes of this inherited inability of melanocytes to synthesize melanin.
Vitiligo: Acquired loss of melanocytes; linked to autoimmune illnesses (Addison's disease, Hashimoto thyroiditis, Grave disease, pernicious anemia); potentially brought on by an autoimmune response or by toxic intermediates of melanocyte formation.
Albinism: May affect the skin and hair (oculocutaneous albinism) or the eyes (ocular albinism); skjn_ contains melanocytes.
Albinism: Hypopigmentation affecting the eyes, skin, and hair; may result in blindness. Vitiligo: Lack of melanocytes in skin.
Vitiligo: Irregular, flat patches of skin loss that typically affect the hands, axillae, or the area surrounding the mouth and eyes. Variable presence of antibodies against antimelanocytes in the lab.
Albinism: Sunscreen is required; there is no known treatment.
Sun protection and topical corticosteroids for vitiligo.
Patients who have vitiligo or albinism are more likely to develop actinic keratoses and skin malignancies.
Albinism : Melanocytes are produced from neural crest ectoderm, hence albinism may be associated to faulty neural crest cell migration. Tyrosinase deficiency or a lack of tyrosine uptake into the melanocyte are the two main causes of this inherited inability of melanocytes to synthesize melanin.
Vitiligo: Acquired loss of melanocytes; linked to autoimmune illnesses (Addison's disease, Hashimoto thyroiditis, Grave disease, pernicious anemia); potentially brought on by an autoimmune response or by toxic intermediates of melanocyte formation.
Albinism: May affect the skin and hair (oculocutaneous albinism) or the eyes (ocular albinism); skjn_ contains melanocytes.
Albinism: Hypopigmentation affecting the eyes, skin, and hair; may result in blindness. Vitiligo: Lack of melanocytes in skin.
Vitiligo: Irregular, flat patches of skin loss that typically affect the hands, axillae, or the area surrounding the mouth and eyes. Variable presence of antibodies against antimelanocytes in the lab.
Albinism: Sunscreen is required; there is no known treatment.
Sun protection and topical corticosteroids for vitiligo.
Patients who have vitiligo or albinism are more likely to develop actinic keratoses and skin malignancies.
