DOWN SYNDROME

DOWN SYNDROME

pediagenosis    June 14, 2021    Comment   

DOWN SYNDROME

Down syndrome is a genetic disorder caused by trisomy of chromosome 21. Trisomy 21 occurs in approximately 1 of every 1000 births. Chromosome 21 is an acrocentric chromosome, and trisomy 21 is the most common form of chromosomal trisomy. Trisomy 21 most often occurs as the result of nondisjunction of meiosis, which leads to an extra copy of chromosome 21. Some patients with Down syndrome have a Robertsonian translocation to chromosome 14 or chromosome 22, which are two other acrocentric chromosomes. In these cases, the number of total chromosomes is normal at 46, but the extra chromosome 21 material is translocated to another chromosome. This, in effect, causes an extra chromo- some 21. All or part of chromosome 21 may be trans-located, leading to variations in phenotype. Mosaicism is a rare cause of trisomy 21 in partial cell lines, and the clinical phenotype depends on how early the genetic defect occurred during embryogenesis.

MARFAN SYNDROME

MARFAN SYNDROME

pediagenosis    June 14, 2021    Comment   

MARFAN SYNDROME

Marfan syndrome is an autosomal dominantly inherited disorder of connective tissue that is caused by a genetic defect in the FBN1 gene located on chromosome 15. The disorder leads to a defect in the fibrillin-1 protein, which is a component of the extracellular matrix of connective tissue. The defect leads to many clinical findings in the cardiovascular, ocular, skeletal, integumentary, and respiratory systems. The diagnosis is made based on multiple criteria that include major and minor features of the syndrome. Cardiovascular disease is a major cause of morbidity and mortality in this syndrome.

EHLERS-DANLOS SYNDROME

EHLERS-DANLOS SYNDROME

pediagenosis    June 14, 2021    Comment   

EHLERS-DANLOS SYNDROME

Ehlers-Danlos syndrome is a heterogeneous disease of defective connective tissue production. There are many subtypes, most caused by defects in collagen formation or in the posttranslational modification of collagen. This grouping of diseases has been confusing because of the variable nature of the subtypes and the lack of a universally adopted classification system. Under the most recent system, there are 7 distinct subtypes; under the historical classification, there were 11 types. The new classification system has not been universally adopted, which contributes to the confusion. As the genetic defects behind each subtype are determined, researchers and clinicians will gain a better understanding of the syndrome.

CUSHING’S SYNDROME: PATHOPHYSIOLOGY

CUSHING’S SYNDROME: PATHOPHYSIOLOGY

pediagenosis    June 14, 2021    Comment   

CUSHING’S SYNDROME: PATHOPHYSIOLOGY

Cushing’s syndrome is directly caused by excessive amounts of glucocorticoids and their effects on numerous organ systems. Cortisol is strikingly elevated in all cases of Cushing’s syndrome. In some cases, levels of 17-ketosteroids and aldosterone are slightly elevated, and this plays a role in the clinical manifestations of the disease. There are numerous disease states that can cause hypercortisolemia, including excessive secretion of adrenocorticotropic hormone (ACTH, corticotropin), adenoma and hyperplasia of the adrenal gland, carcinoma of the adrenal gland, primary pigmented nodular adrenocortical disease (PPNAD), and exogenous cortisol use. In all cases, it is the marked elevation of cortisol that ultimately is the cause of the disease.

CUSHING’S SYNDROME AND CUSHING’S DISEASE

CUSHING’S SYNDROME AND CUSHING’S DISEASE

pediagenosis    June 14, 2021    Comment   

CUSHING’S SYNDROME AND CUSHING’S DISEASE

Cushing’s syndrome is caused by excessive secretion of endogenous glucocorticoids or, more frequently, by intake of excessive exogenous glucocorticoids. The latter type is typically iatrogenic in nature. The excessive glucocorticoid levels lead to the many cutaneous and systemic signs and symptoms of Cushing’s syndrome and Cushing’s disease. Endogenous glucocorticoids are made and secreted by the adrenal glands, and benign adrenal adenomas are the most frequently implicated adrenal tumors causing Cushing’s syndrome. Cushing’s disease is caused by excessive secretion from the anterior pituitary of adrenocorticotropic hormone (ACTH, corticotropin) as the result of a basophilic or chromophobe adenoma. The increased amount of ACTH causes the adrenal glands to hypertrophy and boost their production of cortisol, eventually leading to a state of hypercortisolism. Excessive release of corticotropin-releasing hormone (CRH) from the para- ventricular nucleus of the hypothalamus can also cause the syndrome. Any tumor that has the ability to produce ACTH also has the potential to cause Cushing’s syndrome. The most frequently reported such tumor is the small cell tumor of the lung, which is able to produce many neuroendocrine hormones including ACTH in large amounts.

CARNEY COMPLEX

CARNEY COMPLEX

pediagenosis    June 14, 2021    Comment   

CARNEY COMPLEX

Carney complex, also known as NAME syndrome (nevi, atrial myxomas, myxoid neurofibromas, ephelides) or LAMB syndrome (lentigines, atrial myxomas, mucocutaneous myxomas, blue nevi), is an autosomal dominantly inherited disorder that affects the integumentary, endocrine, cardiovascular, and central nervous systems. This rare disorder is primarily caused by a genetic mutation in the tumor suppressor gene, PRKAR1A. Approximately 20% of patients have defects in an undescribed gene located at 2p16. Various genotypes and phenotypes exist, and the diagnosis is based on a complex list of major, supplemental, and minor criteria.

BASAL CELL NEVUS SYNDROME

BASAL CELL NEVUS SYNDROME

pediagenosis    June 09, 2021    Comment   

BASAL CELL NEVUS SYNDROME

Basal cell nevus syndrome (BCNS), also known as nevoid basal cell carcinoma syndrome or Gorlin syndrome, is an uncommon autosomal dominant genodermatosis caused by mutations in the patched-1 (PTCH1) gene on chromosome 9. Approximately 40% of cases represent new, spontaneous mutations. Affected individuals are predisposed to the development of multiple basal cell carcinomas (BCCs), often in the hundreds over their lifetime. The diagnosis of this syndrome is based on a number of established criteria.

AMYLOIDOSIS

AMYLOIDOSIS

pediagenosis    June 09, 2021    Comment   

AMYLOIDOSIS

The term amyloidosis refers to a heterogeneous group of diseases. Systemic and cutaneous forms of amyloidosis can occur and are caused by the deposition of one of many different amyloid proteins. The primary cutaneous forms are more frequently seen. They include nodular, lichen, and macular amyloidosis (also referred to as lichen or macular amyloidosis). The systemic form is a multisystem, life-threatening disorder that requires systemic therapy. Most systemic disease is caused by an abnormality in plasma cells; myeloma-associated amyloid is a distant second in incidence. In addition to amyloidosis of the skin, the central nervous system may be involved with amyloidosis, as it is in Alzheimer’s disease.

ADDISON’S DISEASE

ADDISON’S DISEASE

pediagenosis    June 09, 2021    Comment   

ADDISON’S DISEASE

Addison’s disease (chronic primary adrenocortical insufficiency) occurs when the adrenal gland has lost most of its functional capacity. Addison’s disease can be caused by many different disease states that inhibit the functioning of the adrenal gland. The adrenal gland has a massive reserve capacity, and clinical manifestations of chronic adrenal insufficiency are not seen until the bilateral glands have lost at least 90% of their ability to produce adrenal hormones. Autoimmune destructive atrophy of the adrenal glands is the most common cause of Addison’s disease. Infectious processes can cause destruction of the adrenal gland, with tuberculosis one of the more common causes of chronic adrenal gland insufficiency. Most cases of acute adrenal gland destruction are caused by bacteria (i.e., meningococcal disease).

WILSON’S DISEASE

WILSON’S DISEASE

pediagenosis    June 09, 2021    Comment   

WILSON’S DISEASE

Wilson’s disease, also known as hepatolenticular degeneration, is a disorder caused by a defect in copper metabolism. The disease is rare, with a worldwide incidence of approximately 1 in 18,000. It is an autosomal recessive condition that is caused by a defect in the ATP7B gene, which is located on the long arm of chromosome 13. The product of this gene is responsible for the proper transport of copper. The main clinical findings relate to nervous system involvement and liver disease. Wilson’s disease has a variable phenotype depending on the specific genetic mutation. Cutaneous disease and ophthalmological disease are frequently seen.

VITAMIN K DEFICIENCY AND VITAMIN K ANTAGONISTS

VITAMIN K DEFICIENCY AND VITAMIN K ANTAGONISTS

pediagenosis    June 09, 2021    Comment   

VITAMIN K DEFICIENCY AND VITAMIN K ANTAGONISTS

POTENTIAL CLINICAL CONSEQUENCES OF WARFARIN USE

Vitamin K is an essential nutrient that is required as a cofactor for the production of a handful of coagulation cascade proteins. It is a fat-soluble vitamin that is efficiently stored in the human body. Vitamin K deficiency is rare and is typically seen only transiently in neonates and infants during the first 6 months of life. Affected neonates may show abnormally prolonged bleeding after minor trauma. Patients may have an elevated pro- thrombin time (PT) and decreased serum levels of vitamin K and coagulation factors. Therapy consists of replacement of vitamin K to normal levels and a search for any possible underlying cause, such as liver or gastrointestinal disease. Neonatal and infantile vitamin K deficiency is most likely caused by maternal breast milk insufficiency of vitamin K.

VITAMIN A DEFICIENCY

VITAMIN A DEFICIENCY

pediagenosis    June 09, 2021    Comment   

VITAMIN A DEFICIENCY

Vitamin A deficiency, also known as phrynoderma, is a multisystem disorder caused by a deficiency of vitamin A, either from lack of intake or from a decrease in normal absorption. Vitamin A is a fat-soluble essential vitamin that is stored in the fatty tissue and liver. Humans require a nutritional source for this vitamin. Foods high in vitamin A include all yellow vegetables (including carrots), green leafy vegetables, liver, milk, eggs, tomatoes, and fish oils. Many other food staples contain vitamin A. Hippocrates may have been the first to describe vitamin A deficiency and a therapy for it. However, it was not until the early twentieth century that scientists recognized the different forms of vitamin A and its carotene precursors.

DERMATOFIBROSARCOMA PROTUBERANS

DERMATOFIBROSARCOMA PROTUBERANS

pediagenosis    May 26, 2021    Comment   

DERMATOFIBROSARCOMA PROTUBERANS

Dermatofibrosarcoma protuberans is a rare cutaneous malignancy that is locally aggressive. The tumor is derived from the dermal fibroblast, and it is not believed to arise from previously existing dermatofibromas. Dermatofibrosarcoma protuberans rarely metastasizes, but it has a distinctive tendency to recur locally.

Clinical Findings: Dermatofibrosarcoma protuberans is a slow-growing, locally aggressive malignancy of the skin. These tumors are low-grade sarcomas and make up approximately 1% of all soft tissue sarcomas. The tumor is found equally in all races and affects males slightly more often than females. Most tumors grow so slowly that the patient is not aware of their presence for many years. The tumor starts off as a slight, fleshcolored thickness to the skin. Over time, the tumor enlarges and has a pink to slightly red coloration. It slowly infiltrates the surrounding tissue, particularly the subcutaneous tissue. If the tumor is allowed to grow long enough, the malignancy will grow into the fat and then back upward in the skin to develop satellite nodules surrounding the original plaque. This is often the reason a patient seeks medical care. The tumor tends to grow slowly for years, but it can hit a phase of rapid growth. This rapid growth phase allows the tumor to grow in a vertical direction, and hence the term protuberans is applied. If medical care is not undertaken, the tumor will to continue to invade the deeper structures, eventually invading underlying tissue, including fascia, muscle, and bone.

MAMMARY AND EXTRAMAMMARY PAGET’S DISEASE

MAMMARY AND EXTRAMAMMARY PAGET’S DISEASE

pediagenosis    May 26, 2021    Comment   

MAMMARY AND EXTRAMAMMARY PAGET’S DISEASE

Extramammary Paget’s disease is a rare malignant tumor that typically occurs in areas with a high density of apocrine glands. It is most commonly an isolated finding but can also be a marker for an underlying visceral malignancy of the gastrointestinal or genitourinary tract. Paget’s disease is an intraepidermal adenocarcinoma confined to the breast; it is commonly associated with an underlying breast malignancy.

Clinical Findings: Extramammary Paget’s disease is most often found in the groin or axilla. These two areas have the highest density of apocrine glands. It is believed that extramammary Paget’s disease has an apocrine origin. There is no race predilection. These tumors most commonly occur in the fifth to seventh decades of life. Women are more often affected than men. The diagnosis of this tumor is often delayed because of its eczematous appearance. It is often misdiagnosed as a fungal infection or a form of dermatitis. Only after the area has not responded to therapy is the diagnosis considered and confirmed by skin biopsy.

KAPOSI’S SARCOMA

KAPOSI’S SARCOMA

pediagenosis    May 26, 2021    Comment   

KAPOSI’S SARCOMA

Kaposi’s sarcoma is a rare malignancy of endothelial cells seen in unique settings. The classic variant is seen in older patients, most commonly individuals living in the region surrounding the Mediterranean Sea. Kaposi’s sarcoma associated with human immunodeficiency virus (HIV) infection or with acquired immunodeficiency syndrome (AIDS) is seen predominantly in men, and the tumor is thought to be caused by human herpesvirus-8 (HHV8). There is also a variant seen in chronically immunosuppressed patients, such as those who have undergone solid organ transplantation. The African cutaneous variant of Kaposi’s sarcoma is seen in younger men in their third or fourth decade of life. Kaposi’s sarcoma is a locally aggressive tumor that rarely has a fatal outcome. The one exception is the very rare African lymphadenopathic form of Kaposi’s sarcoma, which is distinct from the more common African cutaneous form.

Clinical Findings: The tumors are very similar in appearance across the subtypes of clinical settings. They usually appear as pink-red to purple macules, papules, plaques, or nodules. In the classic form of Kaposi’s sarcoma, the tumors are most often found on the lower extremities of older men. Some tumors in this setting remain unchanged for years, and the patient often dies of other causes. Occasionally, the tumors grow and ulcerate, causing pain and bleeding. The disseminated form of classic Kaposi’s sarcoma can be very aggressive, and patients require systemic chemotherapy.

KERATOACANTHOMA

KERATOACANTHOMA

pediagenosis    May 26, 2021    Comment   

KERATOACANTHOMA

The keratoacanthoma is a rapidly growing malignant tumor of the skin that is derived from the keratinocyte. The tumor is believed by many to be a subset of squamous cell carcinoma of the skin, but its natural history and morphology are distinct enough to merit a separate discussion. Most keratoacanthomas are solitary, but many rare variants have been well documented. These variants include the Ferguson-Smith, Witten-Zak, and Grzybowski syndromes.

Clinical Findings: The classic solitary keratoacanthoma starts as a small, flesh-colored papule that rapidly enlarges to form a crateriform nodule with a central keratin plug. The tumor is unique in that, if left alone, the keratoacanthoma will spontaneously resolve after a few weeks to months. The nonclassic form of keratoacanthoma does not spontaneously resolve, and it is inadvisable to leave these tumors alone, because a high percentage will continue to enlarge. If left alone, these tumors can behave aggressively, with local invasion as well as distant metastasis. The most common area of metastasis is the regional lymph nodes. The most common variant of keratoacanthoma is the solitary variant. This almost exclusively occurs in sun-exposed regions of the body. The peak age at onset is in the fifth to sixth decades of life. These tumors are more common in the Caucasian population, and there is slight male preponderance.

MELANOMA

MELANOMA

pediagenosis    May 26, 2021    Comment   

MELANOMA

Malignant melanoma is one of the few types of cancers that has continued to increase in incidence over the past century. Currently, the incidence of melanoma in the United States is 1 in 75 Caucasians; this is projected to continue to increase over the next few decades. However, the rate of mortality from melanoma has dropped, probably as a result of early detection and surgical intervention. According to cancer registries, melanoma ranks sixth in incidence for men and seventh for women. Melanoma is the most common cancer in women aged 25 to 30 years. Approximately 700,000 cases of melanoma were diagnosed in the United States in 2009, and approximately 9000 people died from complications directly related to melanoma.

Clinical Findings: Melanoma follows a characteristic growth pattern. The tumor arises de novo from previously normal skin in approximately 60% of cases and from preexisting melanocytic nevi in the remaining 40% of cases. Melanoma is uncommon in children, the one exception being melanoma arising from giant congenital nevi. The incidence of melanoma peaks in the third decade of life and remains fairly stable over the next 5 decades. There is no gender predilection. Melanoma is more common in the Caucasian population. There are regional variances in distribution of melanoma. The back is more commonly involved in men and the posterior lower legs in women. However, melanoma has been described to occur in any area of the skin and mucous membranes. Melanoma has also been shown to develop within the retinal melanocytes, causing retinal melanoma. This rare tumor is often found incidentally on routine ophthalmological examination.

MERKEL CELL CARCINOMA

MERKEL CELL CARCINOMA

pediagenosis    May 26, 2021    Comment   

MERKEL CELL CARCINOMA

Merkel cell carcinoma is an uncommonly encountered neuroendocrine malignant skin tumor that has an aggressive behavior. This tumor is derived from specialized nerve endings within the skin. The tumor promoting Merkel cell polyomavirus has been implicated in its pathogenesis. The prognosis of Merkel cell carcinoma is worse than that of melanoma. This tumor has a high rate of recurrence and often has spread to the regional lymph nodes by the time of diagnosis.

Clinical Findings: Merkel cell carcinoma is a rare cutaneous malignancy with an estimated incidence of 1 in 200,000. Merkel cell carcinoma is much more common in Caucasian individuals. The tumor has a slight male predilection. The average age at onset is in the fifth to seventh decades of life. The lesions occur most often on the head and neck. This distribution is consistent with the notion that chronic sun exposure is a predisposing factor in the development of this tumor. These tumors also occur more commonly in patients taking chronic immunosuppressive medications. The tumors often appear as red papules or plaques that quickly increase in size. They can also appear as rapidly enlarging nodules. On occasion, the tumor ulcerates. The clinical differential diagnosis is often between Merkel cell carcinoma and basal cell carcinoma, inflamed cyst, squamous cell carcinoma, or an adnexal tumor. These tumors are so rare that they are infrequently in the original differential diagnosis.

SEBACEOUS CARCINOMA

SEBACEOUS CARCINOMA

pediagenosis    April 29, 2021    Comment   

SEBACEOUS CARCINOMA

Sebaceous carcinoma is a rare malignant tumor of the sebaceous gland. These tumors are most frequently seen on the eyelids. They are most commonly found as solitary tumors but may be seen as a part of the Muir-Torre syndrome. The Muir-Torre syndrome is caused by a genetic abnormality in the tumor suppressor genes MSH2 and MLH1 and is associated with multiple sebaceous tumors, both benign and malignant. The syndrome is also associated with a high incidence of internal gastrointestinal and genitourinary malignancies.

Clinical Findings: These tumors are most commonly found on the eyelid skin and the eyelid margin. The reason is that the periocular skin contains many types of modified sebaceous glands, including the meibomian glands and the glands of Zeis. Many other, less common modified sebaceous glands exist, including the caruncle glands and the multiple sebaceous glands associated with the hairs of the periocular skin. It is believed that most sebaceous carcinomas arise from the meibomian glands, with the glands of Zeis the second most common site of origin. The meibomian glands are modified sebaceous glands that are located within the tarsal plate of the upper and lower eyelid.

SQUAMOUS CELL CARCINOMA

SQUAMOUS CELL CARCINOMA

pediagenosis    April 28, 2021    Comment   

SQUAMOUS CELL CARCINOMA

Squamous cell carcinoma (SCC) of the skin is the second most common skin cancer after basal cell carcinoma. Together, these two types of carcinoma are known as non-melanoma skin cancer. SCC accounts for approximately 20% of all skin cancers diagnosed in the United States. SCC can come in many variants, including in situ and invasive types. Bowen’s disease, bowenoid papulosis, and erythroplasia of Queyrat are all forms of SCC in situ. A unique subtype of SCC is the keratoacanthoma. Invasive SCC is defined by invasion through the basement membrane zone into the dermis. SCC has the ability to metastasize; the most common area of metastasis is the local draining lymph nodes. Most forms of cutaneous SCC occur in chronically sundamaged skin, and they are often preceded by the extremely common premalignant actinic keratosis.

Genital Squamous Cell Carcinoma

Clinical Findings: SCC of the skin is most commonly located on the head and neck region and on the dorsal hands and forearms. These are the areas that obtain the most ultraviolet sun exposure over a lifetime. This type of skin cancer is more common in the Caucasian population and in older individuals. It is more prevalent in the fifth to eighth decades of life. The incidence of SCC increases with each decade of life. This form of non-melanoma skin cancer is definitely linked to the amount of sun exposure one has had over one’s lifetime. Fair-skinned individuals are most commonly affected. There is a slight male predilection. Other risk factors include arsenic exposure, human papillomavirus (HPV) infection, psoralen + ultraviolet A light (PUVA) therapy, chronic scarring, chronic immunosuppression, and radiation exposure. Transplant recipients who are taking chronic immunosuppressive medications often develop SCCs. Their skin cancers also tend to occur on the head and neck and on the arms, but in addition they have a higher percentage of tumors developing on the trunk and other non–sun-exposed regions.