Sec 24 Skin in Nutritional, Metabolic and Heritable Disease Pt 2 Flashcards
1
Q
X-linked disease which is the second most prevalent lysosomal storage disorder, (after Gaucher disease) caused by the partial or complete deficiency of a lysosomal enzyme, α-galactosidase A
A
Fabry Disease
2
Q
Cutaneous hallmark of Fabry disease present in 70% of males and 39% of females which are pinpoint to 4-mm diameter, dark-red to blue-black, macular, and papular lesions, which do not blanch on pressure
A
Angiokeratoma
3
Q
Histopathology: Dilated, ectatic capillaries in the papillary dermis, a variably thinned epidermis centrally, with epidermal acanthosis at the edges of the lesion (colarette), and variable degrees of overlying focal compact orthohyperkeratosis
A
Angiokeratoma
4
Q
The “pseudoacromegalic” facial features in Fabry disease (decreasing order)
A
periorbital fullness prominent ear lobes bushy eyebrows recessed forehead pronounced nasal angle generous nose/bulbous nasal tip prominent supraorbital ridges shallow midface full lips prominent nasal bridge broad alar base coarse features posteriorly rotated ears prognathism
5
Q
Classical feature of Fabry disease and thought largely to be a consequence of autonomic neuropathy
A
Reduced sweating or hypohidrosis
6
Q
A frequent complaint amongst Fabry disease patients of pain in the extremities in cold environments
A
Raynaud phenomenon
7
Q
This occur in 80%–90% of Fabry disease patients typically occur in the first decade described as sensation as pain, feeling like pins and needles in hands and feet, often radiating proximally, triggered by increased body temperature, exercise, or stress due to damage to nerve fibers as a result of inflammation and substrate accumulation.
A
Acroparesthesia
8
Q
Most common ocular finding in Fabry disease characterized as opacities in the cornea characterized by one or more lines radiating from the near the center of the cornea
A
Cornea verticillata
9
Q
Constant feature and increasingly recognized as the major cause of death in Fabry patients both male and female
A
Cardiac manifestations
10
Q
Often reported as the presenting feature of Fabry disease
A
Stroke affecting the posterior circulation
11
Q
Definitive Diagnosis for Fabry disease
A
Demonstration of deficient α-galactosidase A activity in plasma, serum, or leukocytes
Identification of a pathogenic mutation
12
Q
X-linked disease starts at age of 5–12 years occuring in both males > females, presents with multiple, clustered dark-red to blue– black macules and papules Larger lesions warty (1–4 mm) affecting any part of the body, especially bathing trunk area, umbilicus, lips and can be associated with acroparesthesias, heart and renal failure, stroke, cornea verticillata, deafness
A
Fabry disease (Angiokeratoma corpus diffusum)
13
Q
AD disease starts at age of 10–15 years, occuring in both, female > males, presents with grouped, warty, dark-red papules (1–5 mm) on the lateral aspect and dorsa of fingers and toes, hands, and feet associated with acrocyanosis and chilblains
A
Angiokeratoma of Mibelli
14
Q
Acquired disease in >60 year old males presenting with multiple warty, blue–black papules (1–4 mm) on the scrotum associated with local venous hypertension
A
Angiokeratoma of Fordyce
15
Q
Acquired disease in >60 female presents with grouped, warty, blue–black papules (1–4 mm) on the vulva associated with local venous hypertension
A
Angiokeratoma of Vulva
16
Q
Acquired seen in 10–40 males and females presents with single dark-red to black keratotic papules (2–10 mm) which often bleeds or thromboses seen on any part of the body, especially in lower extremities
A
Solitary angiokeratoma
17
Q
Acquired usually early onset or at birth presents with unilateral plaque keratotic dark-red papules, may bleed
on the lower legs or foot may be associated with Cobb syndrome or vascular malformations
A
Angiokeratoma circumscriptum
18
Q
Typical symptoms of Fabry disease at childhood and adolescence (≤16 years)
A
Pain (acroparesthesia) particularly in the extremities
Angiokeratomas
Ophthalmological abnormalities (cornea verticillata and tortuous retinal blood vessels)
Hearing impairment
Dyshidrosis (hypohidrosis and hyperhidrosis)
Hypersensitivity to heat and cold
Gastrointestinal disturbances and abdominal pain
Lethargy and tiredness
Onset of renal and cardiac signs, e.g., proteinuria, arrhythmia
19
Q
Typical symptoms of Fabry disease at early adulthood (17–30 years)
A
Extension of childhood symptoms
Proteinuria and progressive renal failure
20
Q
Typical symptoms of Fabry disease at late adulthood (age >30 years)
A
Worsening of any childhood to early adulthood symptoms
Heart disease (e.g., left ventricular hypertrophy, angina, arrhythmia, and dyspnea)
Stroke and transient ischemic attacks
Osteopenia and osteoporosis
21
Q
Disease with deficiency in β-Galactosidase with mutation on gene 3p21– 3pter presents with facial dysmorphism, hematologic signs, mental retardation, organomegaly and AK corporis diffusum
EM findings: Electron-lucent lysosomal dilation
A
GM1 gangliosidosis
22
Q
Disease with deficiency in Aspartylglycosaminidase with mutation on gene 4q32–33 presents with coarse facies, macroglossia, organomegaly, ocular findings, cardiac valve involvement, AK corporis diffusum, facial angiofibromas, oral fibromatosis and leukokeratosis
EM findings: Electron-lucent lysosomal dilation
A
Aspartylglucosaminuria
23
Q
Disease with deficiency in α-Fucosidase with mutation on gene 1p34 presents with mental retardation, coarse facies, growth retardation, recurrent respiratory infections, dysostosis multiplex, visceromegaly, AK corporis diffusum, widespread telangiectasias, acrocyanosis, purple transverse distal nail bands, increased vasculature in hands and feet, and sweating abnormalities
EM findings: Electron-lucent lysosomal dilation
A
Fucosidosis
24
Q
Disease with deficiency in β-Mannosidase with mutation on gene 4q22-q25 presents with mental retardation, neuropathy, hearing loss, recurrent infections and AK corporis diffusum in bathing trunk area
EM findings: Electron-lucent lysosomal dilation
A
β-Mannosidosis
25
Disease with deficiency in Neuraminidase with mutation on gene 6p21.3 presents with mental retardation, dysostosis multiplex, vacuolated lymphocytes, subtle coarse facial features and AK corporis diffusum
EM findings: Electron-lucent lysosomal dilation
Sialidosis II
26
Disease with deficiency in β-Galactosidase and neuraminidase with mutation on gene 20q13.1 presents with dwarfism, gargoyle facies, mental retardation, seizures, corneal clouding, dysostosis multiplex, hearing loss and AK corporis diffusum scattered along entire body, especially knees, elbows, and bathing trunk area
EM findings: Electron-lucent lysosomal dilation
Galactosialidosis
27
Disease with deficiency in α-N-acetylgalactosaminidase (α-Nacetylgalactosaminidase) with mutation on gene 22q11 presents with mental retardation, coarse facial features, ocular signs, hearing loss, neuropathy, AK corporis diffusum of entire body (more dense on the bathing trunk area, axillae, breasts) and telangiectasias on lips and oral mucosa
EM findings: Electron-lucent lysosomal dilation
Kanzaki
28
Treatment: Angiokeratomas (Fabry disease)
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Liquid nitrogen
Electrocoagulation
Surgical excision
Laser (pulsed-dye 585-nm, neodymium YAG 1,064 nm, combined pulsed-dye and Nd:YAG)
Intense pulsed light (IPL)
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29
Treatment: Lymphedema (Fabry disease)
Manual lymphatic drainage massage and compression
30
Treatment: Hyperhidrosis (Fabry disease)
Aluminium chloride hexahydrate
Electrophoresis
Botulinum toxin
Glycopyrrolate sodium
31
Treatment: Raynaud Phenomenon (Fabry disease)
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Avoid smoking
Cold and vasoconstrictor therapies
Losartan
Diltiazem
Fluoxetine
Sildenafil
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32
Treatment: Pain (Fabry disease)
Avoid triggers
Carbamazepine
Gabapentin
33
Treatment: Stroke (Fabry disease)
Antiplatelet
| Anticoagulant
34
Treatment: Gastrointestinal (Fabry disease)
Pancrelipase
| Metoclopramide
35
Treatment: Cardiovascular (Fabry disease)
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Antihypertensive drugs
Antiarrhythmic drugs
Artificial pacemakers
Implantable defibrillators
Coronary bypass
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36
Treatment: Chronic Renal Failure (Fabry disease)
Angiotensin converting enzyme inhibitors
Hemodialysis
Allograft transplant
37
Treatment: Specific in Fabry disease
Enzyme replacement
α-Galactosidase B (Fabrazyme)
α-galactosidase A (Replagal)
38
Regulates major functions in the epidermal keratinocytes including proliferation, differentiation, and cell-cell adhesion
Calcium
39
Three regulatory hormones that control the ionic calcium concentration in serum
1. parathyroid hormone (PTH)
2. calcitonin
3. 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)
40
Primary stimulant for calcitonin secretion
Calcium
41
Increases renal tubular reabsorption of calcium and increases renal clearance of phosphate; imulates osteoclastic bone resorption, possibly by stimulating osteoblasts to release factors that activate osteoclasts
Parathyroid hormone
42
Increases the concentration of plasma calcium with primary action to stimulate the active transport of calcium across the intestine; also plays a major role in the growth and differentiation of tissues
Vitamin D3
43
Deposition of insoluble calcium salts in the skin
Calcinosis cutis
44
Most common type of calcinosis cutis and occurs as a result of local tissue injury; frequently occurs in connective tissue diseases
Dystrophic calcification
45
Precipitation of calcium salts in normal tissue secondary to an underlying defect in calcium and/or phosphate metabolism
Metastatic calcification
46
Occurs without identifiable underlying tissue abnormalities, abnormal calcium, and/or phosphate metabolism
Idiopathic calcification
47
Nodules and plaques of calcium deposits occur in the skin, subcutaneous tissue, muscle, or tendons most commonly occur on the upper extremities, especially on the fingers and wrists, but may occur in any area subject to trauma or motion
Dystrophic calcification
48
Lobular panniculitis that commonly demonstrates dystrophic calcification that occurs in patients with pancreatitis or pancreatic adenocarcinoma and caused by the action of liberated pancreatic enzymes on subcutaneous fat
Pancreatic enzyme panniculitis
49
Presents with erythematous, well-defined nodules and plaques occur during the first few weeks of life over the cheeks, back, buttocks, and extremities that usually clear spontaneously affecting infants that are generally otherwise healthy
Subcutaneous fat necrosis of the newborn
50
Subcutaneous calcified nodules and are thought to represent calcified ischemic fat lobules
Spheroids
51
Most common cutaneous neoplasm that manifest calcification (in 75%) and ossification (15-20%)
Pilomatricoma
52
Neoplasms that are associated with calcification and ossification
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Pilar cyst
Basal cell carcinoma
Intradermal nevi
Desmoplastic malignant melanoma
Atypical fibroxanthoma
Pyogenic granuloma
Hemangioma
Neurilemmoma
Trichoepithelioma
Seborrheic keratoses.
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53
Most commonly occurs in chronic renal failure and takes the form of either benign nodular calcification or calciphylaxis
Metastatic calcification
54
Life-threatening disorder characterized by progressive vascular calcification, soft tissue necrosis, and ischemic necrosis of the skin which presents as firm, extremely painful, well-demarcated, violaceous plaques associated with soft tissue necrosis and ulceration
Calciphylaxis
55
Histopathology: medial calcification of small and medium-sized arteries with intimal hyperplasia, primarily in dermal and subcutaneous tissues
Calciphylaxis
56
Due to chronic ingestion of vitamin D in supraphysiologic doses (50,000–100,000 units/day) with initial signs and symptoms include weakness, lethargy, headache, nausea, and polyuria attributable to hypercalcemia and hypercalciuria
Hypervitaminosis D
57
Characterized by excessive ingestion of calcium-containing foods or antacids, leading to hypercalcemia
Milk–alkali syndrome
58
Disorder characterized by the deposition of calcific masses around major joints, such as hips, shoulders, elbows, and knees
Tumoral calcinosis
59
Familial type of Tumor calcinosis is caused by what mutation
Inactivating mutations in either the GALNT3 or FGF23 genes
60
Treatment of choice: calcification of the scrotum
Excision (of the lesions)
61
Three well-described ossifying syndromes
1. Fibrodysplasia ossificans progressiva (FOP)
2. Albright hereditary osteodystrophy (AHO)
3. Progressive osseous heteroplasia (POH)
62
AD syndrome characterized by the progressive ossication of deep connective tissue presents with abnormal phalanges of the hands, deafness, baldness, and mental retardation
Fibrodysplasia ossificans progressiva (FOP)
63
Bone morphogenic protein type I receptor and its mutation leads to overactive BMP signaling, leading to ectopic bone formation
ACVR1 or ALK2
64
Characteristic feature of FOP
Dysmorphic great toes
65
Negative regulator of bone formation, have been identified in both AHO and POH
G protein of adenyl cyclase (GNAS1)
66
AD inherited syndrome characterized by the ossification of cutaneous and subcutaneous tissues in childhood which follows a limited course presents with brachydactyly dimpling over the metacarpophalangeal joints (Albright’s sign), obesity, round or moon facies, short stature, and mental retardation; have a deficient end-organ response to PTH or “pseudohypoparathyroidism” with hypocalcemia, hyperphosphatemia, and elevated levels of PTH
Albright hereditary osteodystrophy (AHO)
67
Characterized by progressive ossification
of skin and deep tissues during infancy or childhood in females presenting with a papular eruption resembling “rice grains” and having a “gritty” consistency; no associated dysmorphic features
Progressive osseous heteroplasia (POH)
68
Most commonly occurs as multiple small, firm nodules on the faces of young women with a history of acne vulgaris.
Miliary osteoma cutis of the face
69
Tuberous Sclerosis is caused by mutations in
Tumor suppressor gene -
TSC1 - chromosome 9q34 encoding hamartin
TSC2 (more severe) - chromosome 16p13.3 encoding tuberin
70
Drug that inhibits mTOR and may be useful for the treatment of internal tumors in Tuberous Sclerosis
Rapamycin
71
Definite Tuberous Sclerosis
Presence of either 2 major features or 1 major feature and 2 minor features
72
Probable Tuberous Sclerosis
Presence of 1 major feature and 1 minor feature
73
Possible Tuberous Sclerosis
Presence of either 1 major feature or 2 or more minor features
74
Major features of Tuberous Sclerosis Complex
Facial angiofibromas or forehead plaque
Nontraumatic ungual or periungual fibromas Hypomelanotic macules (three or more)
Shagreen patch (connective tissue nevus)
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Multiple retinal nodular hamartomas
Cortical tubera
Subependymal nodule
Subependymal giant cell astrocytomas
Cardiac rhabdomyoma, single or multiple Lymphangiomyomatosis
Renal angiomyolipomas
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75
Minor features of Tuberous Sclerosis Complex
Multiple randomly distributed pits in dental enamel
Gingival fibromas
Confetti skin lesions
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Hamartomatous rectal polyps
Bone cysts
Cerebral white matter migration lines
Nonrenal hamartoma
Retinal achromic patch
Multiple renal cysts
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76
Observed in over 90% of children often present at birth or appear within the first few years of life and may fade or disappear in adulthood which typically measure 0.5–3.0 cm in diameter, off-white and not completely depigmented as in vitiligo
Hypomelanotic macules
77
Hypomelanotic macules that are oval at one end and taper to a point at the other that can be located anywhere on the body but tend to occur most often on the trunk and buttocks
Ash-leaf spots
78
Appear at 2–5 years of age and eventually affect 75-90% of patients may number from 1 to over 100, 1–3 mm in diameter pink to red papules with smooth surface which may be hyperpigmented usually unilateral occur on the central face and are often concentrated in the alar grooves extending symmetrically onto the cheeks and to the nose, nasal opening, and chin, with relative sparing of the upper lip and lateral face
Angiofibroma
79
May be congenital or show gradual development over years present in 20-40% of patients which an irregular, soft to firm, connective tissue nevus may be skin-colored, red or hyperpimented found on the scalp, cheeks or elsewhere on the face
Fibrous facial plaque
80
1-10cm firm or rubbery irregular plaque observed in 50% of patients which may be present in infancy but usually becomes apparent later, may be skin-colored, or slightly pink or brown most commonly located on the lower back and buttocks found less commonly on the thighs
Shagreen patch
81
1mm to 1cm red papules and nodules that are firm, pointed, and hyperkeratotic, or soft and rounded that appear after the first decade and eventually affect up to 88% of adults, more common on the toes than on fingers arise from under the proximal nail fold and under the nail plate
Koenen’s tumors or Ungual fibroma
82
Multiple skin colored or hyperpigmented fibroepithelial polyps in Tuberous Sclerosis patients
Molluscum fibrosum pendulum
83
Patches of multiple minute papules, usually on the neck or trunk that appear like “goose flesh" in Tuberous Sclerosis patients
Miliary fibromas
84
Benign thickening of the proximal fingers in Tuberous Sclerosis patients
Pachydermodactyly
85
Tiny pinpoint lesions or larger crater-like lesions observed in 100% of Tuberous Sclerosis patients that occur on both deciduous and permanent teeth
Dental pitting
86
Classic triad of Tuberous Sclerosis
Seizures
Mental retardation
Angiofibromas
87
Occur in 6-14% of individuals with Tuberous Sclerosis. which may increase intracranial pressure and cause headache, vomiting, and bilateral papilledema
Subependymal giant cell astrocytomas
88
Asymptomatic neoplasms that often regress seen in 50-70% of infants with Tuberous Sclerosis, may cause fetal hydrops and stillbirth or heart failure shortly after birth, or may cause dysrhythmias, commonly Wolff-Parkinson-White syndrome
Cardiac rhabdomyomas
89
Seen in 75% of Tuberous Sclerosis patients over 10 years of age which may cause cause renal insufficiency, hypertension, and potentially fatal retroperitoneal hemorrhage
Angiomyolipomas
90
Histopathology: Contain plump, spindle-shaped, or stellate broblastic cells in the dermis among increased numbers of dilated vessels. Collagen fibers are oriented in an onionskin pattern around follicles and vessels. The epidermis shows melanocytic hyperplasia and flattening of rete ridges.
Angiofibroma
91
Initial evaluation of a patient suspected to have Tuberous Sclerosis includes
1. Cranial computed tomography (CT) or cranial magnetic resonance imaging (MRI)
2. Renal ultrasonography (or MRI or CT)
3. Electrocardiography
92
Group of inherited disorders that share in common developmental defects involving at least two of the major structures classically held to derive from the embryonic ectoderm—hair, teeth, nails, and sweat glands
Ectodermal dysplasias
93
Defective gene - protein:
| X-linked Hypohidrotic Ectodermal Dysplasia
EDA, EDA1, HED - ectodysplasin
| at Xq12-13.8
94
Most frequent signs in X-linked Hypohidrotic Ectodermal Dysplasia
Patchy hypotrichosis
| Hypodontia
95
Affected males may present at birth with a collodion membrane or with marked scaling of the skin, scalp hair sparse, fine, and blonde and other body hair is usually sparse or absent; ability to sweat is compromised with heat intolerance; sweat pores undetectable and fingerprint ridges effaced; periorbital wrinkling and hyperpigmentation are typical
X-linked Hypohidrotic Ectodermal Dysplasia
96
Early clue to the diagnosis of X-linked Hypohidrotic Ectodermal Dysplasia
Hypoplastic gum ridges
97
Defective gene:
| Hidrotic Ectodermal Dysplasia
GJB6 or connexin-30
98
AD with variable expression equally affecting males and females presents with wiry, brittle and pale scalp hair with patchy alopecia progressing to total alopecia in adults;
nails may be milky white in infancy gradually thickening and becoming dystrophic with thick, short and slow growing nail plates; normal sweating and teeth conjunctivitis and blepharitis, possibly due to poor function of sparse eyelashes, are common.
Hidrotic Ectodermal Dysplasia
99
Histopathology: thickened palms and soles show orthohyperkeratosis with a normal granular layer
Electron microscopy: increased number of desmosomes in the stratum corneum
Hidrotic Ectodermal Dysplasia
100
Defective gene:
Ankyloblepharon Filiforme Adnatum-Ectodermal Dysplasia-Cleft Palate Syndrome (Hay-Wells Syndrome)
Rapp-Hodgkin syndrome
p63 tumor-suppressor gene
101
AD disorder that presents at birth with shiny red, cracking, peeling skin, and superficial erosions (80-90%), patchy alopecia, with wiry, coarse, and light-colored scalp hair with an uncombable hair appearance, sparseness to absence of body hair, strands of skin between the eyelids (70%), effaced dermatoglyphics and palmoplantar erosive changes but normal sweating, cleft palate +/- cleft lip, (80-100%)
Hay-Wells Syndrome
102
Presents with face with short nasal columella and maxillary hypoplasia, thin upper lip, and full lower lip, hypohidrosis usually without episodes of frank hyperpyrexia, abnormal hair with pili torti or pili trianguli et canaliculi and progressive balding, along with nail dystrophy, nails are thick and short, worsening with age; teeth may be conical and prone to caries
Rapp-Hodgkin syndrome
103
Histopathology: mild epidermal atrophy, focal orthokeratosis, prominent superficial vascular plexus, and pigment incontinence with melanophage
Ankyloblepharon Filiforme Adnatum-Ectodermal Dysplasia-Cleft Palate Syndrome (Hay-Wells Syndrome)
Rapp-Hodgkin syndrome
104
Defective gene:
| Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate (EEC) syndrome
p63 tumor-suppressor gene
105
AD disorder with variable expression and reduced penetrance presents with blond, coarse, and dry hair which may be sparse and slow growing; dystrophic nails with transverse ridging, pitting, and slow growth; dry skin with thickening of the palms and soles; normal sweating; abnormal development of the median rays of the hands and feet; cleft palate +/- cleft lip (70-100%), hypodontia and premature loss of secondary teeth
Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate (EEC) syndrome
106
Defective gene:
| Tooth and Nail Syndrome (Witkop Syndrome; Hypodontia with Nail Dysgenesis)
MSX1
107
AD disorder with thin, small, and friable nails which may show koilonychia at birth (toenails > fingernails) and may improve with age and may with small primary teeth and secondary teeth may fail to erupt
Tooth and Nail Syndrome
108
Defective gene:
| Focal dermal hypoplasia of Goltz
PORCN
109
X-linked dominant disorder, usually lethal in males presents with linear, punctate, streaky cribriform atrophy
Focal dermal hypoplasia of Goltz
110
Defective gene-protein:
| Neurofibromatosis-1
NF-1 - neurofibromin
| chromosome 17
111
Diagnostic Criteria for Neurofibromatosis-1 (2 or more)
1. 6 or more café-au-lait macules over 5 mm in greatest diameter in prepubertal individuals, and over 15 mm in postpubertal individuals
2. 2 or more neurofibromas of any type or 1 plexiform neurofibroma
3. Freckling in the axillary or inguinal regions
4. Optic glioma
5. 2 or more iris Lisch nodules
6. A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex with or without pseudarthrosis
7. A first-degree relative (parent, sibling, or offspring) with NF-1 by the above criteria
112
AD disorder with variable expression presents with café-au-lait macules, neurofibromas, axillary/inguinal freckling, optic glioma, iris Lisch nodules and osseous lesions such as sphenoid dysplasia or thinning of long bone cortex with or without pseudarthrosis
Neurofibromatosis-1
113
Found in a variety of cell types, including neurons, oligodendrocytes, and nonmyelinating Schwann cells and has a role of downregulating the downstream effects of RAS, which include promoting learning, memory, synaptic plasticity, and cell growth and proliferation
Neurofibromin
114
Flat, pigmented macules, frequently present at birth and
become more numerous as the infant grows and continue to appear throughout the first decade of life which represent collections of heavily pigmented melanocytes of neural crest origin in the epidermis in NF-1 (53% by age 3 years and 97% by age 6 years)
Cafe-au-lait macules
115
Café-au-lait spots smaller than 5 mm not related to sun exposure, present in the axillae, inguinal region, and under the breasts and are considered pathognomonic of NF-1 (Crowe’s sign)
Intertriginous freckling
116
Consist of Schwann cells, mast cells, fibroblasts, and perineural cells, are benign nerve sheath tumors that appear as discrete masses arising from peripheral nerves
Neurofibromas
117
Protrudeabove the skin surface or lie just under the skin with an overlying violaceous hue which are softer than the surrounding connective tissue, often creating a “buttonholing” sensation when a finger is rubbed gently over the surface
Cutaneous neurofibromas
118
Arise from peripheral nerves, both under the skin and deep in the viscera, are generally much harder; may grow through neural foramina if they arise from the dorsal root ganglia, compressing the spinal cord, creating a “dumbbell” appearance; in the neck may feel like a “beaded necklace,” often being confused with lymph nodes
Subcutaneous neurofibromas
119
Histologically similar to discrete neurofibromas which are benign peripheral nerve sheath tumors which involve single or multiple nerve fascicles, often arising from branches of major nerves; may elicit a “wormy” sensation on palpation; there is overlying hyperpigmentation (“giant café-au-lait spot”) or hypertrichosis present at birth or become apparent during the first several years of life
Plexiform neurofibromas
120
Period of greatest risk for the development of symptomatic Optic Pathway Tumors in NF-1
First 6 years of life
121
Accelerated linear growth and the development of secondary sexual characteristics can be can be aborted with
Long-acting luteinizing hormone releasing hormone agonist
122
Ophthalmologic signs of Optic Pathway Tumors in NF-1
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Afferent papillary defect
Optic nerve atrophy
Papilledema
Strabismus
Defects in color vision
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123
Slightly raised, well-circumscribed melanocytic hamartomas of the iris pathognomonic of NF-1 best seen using a slit lamp, and do not cause any functional impairment of vision (30% of children, 90% in adults)
Lisch nodules
124
Two bony lesions distinctive enough to be included in the diagnostic criteria for NF-1:
1. Dysplasia of the wing of the sphenoid bone
| 2. Dysplasia of a long bone - MC tibia
125
Most common skeletal manifestation of NF-1,
| affecting 10%–30% of patients
Scoliosis
126
Result of primary bone dysplasia, and may present very early in childhood, typically resulting in a sharply angulated curve spanning relatively few vertebral bodies; often accompanied by extreme rotation, scalloping of the posterior margins of the vertebral bodies, vertebral wedging, defective pedicles, and enlargement of the neural foramina and spinal canal
Dystrophic scoliosis
127
Almost exclusively arise from preexisting plexiform neurofibromas with lifetime risk for the development as high as 13%
Malignant peripheral nerve sheath tumors
128
Associated with NF-1 with an incidence of 1.4%, mean age at presentation was 42 years; may present with catecholamine-associated symptoms and hypertension
Pheochromocytoma
129
Leukemia associated in children with NF-1
Chronic myelomonocytic leukemia
| Acute lymphoblastic leukemia
130
Presents with yellowish papules less than 1 cm in diameter that are usually found on the head or trunk associated with NF-1
Juvenile xanthogranuloma
131
Most commonly identified vascular lesion in patients with NF-1
In renal artery leading to renovascular hypertension
132
Diagnosis: Renal artery vasculopathy
Aortography with selective angiography of the renal arteries
133
Regions of increased signal intensity on T2-weighted images on brain magnetic resonance imaging of children with NF-1 in the internal capsule, basal ganglia, cortex, cerebellar hemispheres, optic tract, or brainstem
Unidentified bright objects
134
Earliest indication of precocious puberty
Accelerated linear growth
135
An antihistamine and mast cell stabilizer, has provided relief from pruritus and pain and prevented the rapid growth of new neurofibromas
Ketotifen
136
An AD inherited condition characterized by bilateral vestibular schwannomas, meningiomas (intracranial, intraspinal, and optic nerve sheath), schwannomas (dorsal roots of the spinal cord, peripheral nerves, and cranial nerves), ependymomas and gliomas of the central nervous system, and juvenile posterior subcapsular cataracts.
Neurofibromatosis-2
137
Characteristic cutaneous lesion of NF-2 which is a plaque-like, slightly raised lesion with a faint violaceous hue, occasionally with hair
Cutaneous schwannoma
138
Defective gene-protein:
| Neurofibromatosis-2
NF-2 - merlin or schwannomin
| chromosome 22
139
Individuals who have manifestations of NF-1, usually café-au-lait macules and neurofibromas, limited to one area of the body are at risk for developing complications of NF-1 in the affected area
Segmental neurofibromatosis
140
Meets the diagnostic criteria of NF-1 with hypertelorism, ptosis, downsloping palpebral fissures, low set, posteriorly rotated ears, webbed neck, pectus deformities, and short stature
Neurofibromatosis-1-Noonan syndrome
141
Develop multiple painful schwannomas within peripheral nerves and paraspinal nerve roots but fail to develop other manifestations of NF-2, particularly vestibular schwannomas
Schwannomatosis
142
Genome instability by increased chromosome breakage in primary blood or skin cells
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Bloom syndrome (BS)
Ataxia telangiectasia
Fanconi anemia (FA)
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143
Genome instability by after exposure to DNA-damaging agents such as UV radiation or other carcinogens
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Xeroderma pigmentosum (XP)
Cockayne syndrome (CS)
Trichothiodystrophy (TTD)
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144
Genome instability from abnormal telomere maintenance
Dyskeratosis congenita
145
Genome instability may result from a defect in BASC (BRCA1-associated genome surveillance complex) a multienzyme complex, containing DNA damage response proteins
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Ataxia-telangiectasia
Seckel syndrome
Nijmegen breakage syndrome
Hereditary breast cancer
Bloom syndrome (BS)
Fanconi anemia (FA)
Hereditary colon cancer
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146
AR disorder of genome instability with defective DNA repair presents with photosensitivity (blistering on minimal sun exposure), freckle-like (lentiginous) macules, poikiloderma (hyper- and hypopigmentation, atrophy, telangiectasia) associated with sensorineural deafness, progressive neurologic degeneration and primary loss of neurons may lead to BCC, SCC, melanoma or central nervous system tumors
Xeroderma pigmentosum (XP)
147
AR disorder of genome instability with defective DNA repair presents with photosensitivity (burning on sun exposure) and with typical facial features (deep set eyes, loss of subcutaneous fat), pigmentary retinal degeneration, postnatal growth failure, sensorineural deafness, progressive neurologic degeneration, primary dysmyelination and brain calcifications
Cockayne syndrome (CS)
148
AR disorder of genome instability with defective DNA repair presents with photosensitivity (blistering on minimal sun exposure), freckle-like (lentiginous) macules, poikiloderma (hyper- and hypopigmentation, atrophy, telangiectasia) associated with neurologic changes may lead to BCC or SCC
Xeroderma pigmentosum/Cockayne syndrome complex (XP/CS)
149
AR disorder of genome instability with defective DNA repair presents with brittle hair, photosensitivity (burning on sun exposure), ichthyosis, collodion membrane, “tiger tail banding” of hair with polarized microscopy associated with congenital cataracts, short stature developmental delay, microcephaly, primary dysmyelination, recurrent infections
Trichothiodystrophy (TTD)
150
AD disorder of genome instability with defective DNA repair presents with sebaceous tumors (benign and malignant), keratoacanthomas may lead to low-grade cancer of the colon, endometrium, stomach, small intestine, hepatobiliary system, upper urethral tract, larynx and ovary; sebaceous carcinoma or BCC with sebaceous differentiation
Hereditary nonpolyposis colon cancer (HNPCC)/Muir–Torre Syndrome (MTS)
151
AR disorder of genome instability presents with photosensitivity (burning on sun exposure), malar erythema, café-au-lait macules associated with immune deficiency, growth retardation, unusual facies, male infertility and female subfertility, type II diabetes; may lead to most cancer types in particular leukemia, lymphomas, carcinomas of the breast and gastrointestinal tract
Bloom syndrome (BS)
152
AR disorder of genome instability presents with graying of hair, skin atrophy, leg ulcers, melanomas associated with premature aging (atherosclerosis, diabetes mellitus, osteoporosis, cataracts) and may lead to sarcomas, thyroid cancer, meningiomas, or melanomas (acral lentiginous, mucous membrane melanomas)
Werner syndrome (WS)
153
AR disorder of genome instability presents with photosensitivity (burning on sun exposure), poikiloderma, alopecia associated with skeletal abnormalities, growth de ciency, juvenile cataracts, osteoporosis may lead to osteosarcomas, cutaneous SCC
Rothmund-Thomson syndrome (RTS)
154
AR disorder of genome instability presents with café-au-lait macules associated with aplastic anemia, pancytopenia, growth retardation, thumb and other bone abnormalities and may lead to myeloid leukemia, or SCC of head and neck
Fanconi anemia (FA)
155
AR/AD/XR disorder of genome instability presents with lacy, reticular pigmentation of neck and upper chest; nail dystrophy; premature gray hair, hyperhidrosis associated with stenosis of lacrimal duct, anemia, pancytopenia, immunodeficiency, learning difficulties, deafness, brain calcifications, cerebellar hypoplasia, testicular atrophy, short stature, intrauterine growth retardation and retinopath and may lead to mucosal leukoplakia leading to cancer of anus or mouth, Hodgkin disease, or pancreatic adenocarcinoma
Dyskeratosis congenita
156
AR disorder of genome instability presents with telangiectasias associated with progressive cerebellar ataxia, immune defects, hypogonadism, and increased acute toxicity of therapeutic X-ray may lead to T-cell leukemia, lymphomas
Ataxia telangiectasia (AT)
157
AR disorder of genome instability Similar to Ataxia telangiectasia, but no ocular telangiectasias
Ataxia telangiectasia-like disorder (ATLD)
158
AR disorder of genome instability presents with Café-au-lait macules and vitiligo associated with immune defects, growth retardation, microcephaly, mental retardation, and characteristic facies may lead to B- and T-cell lymphomas, rhabdomyosarcoma or neuroblastoma
Nijmegen breakage syndrome (NBS)
159
AR disorder of genome instability presents with Café-au-lait macules associated with proportionate dwarfism, microcephaly, mental retardation, characteristic facies (receding forehead, narrow face, large beaked nose, micrognathia), immune deficiency and pancytopenia; may lead to leukemia
Seckel syndrome
160
Involves the cutaneous and ocular manifestations of classic XP plus additional neurologic and somatic abnormalities, including microcephaly, progressive mental deterioration, low intelligence, hyporeflexia or areflexia, choreoathetosis, ataxia, spasticity, Achilles tendon shortening leading to eventual quadriparesis, dwarfism, and immature sexual development
De Sanctis-Cacchione syndrome
161
Believed to be the basis of the increased frequency of sunlight-induced somatic mutations that lead to cancer in XP patients
Post-UV hypermutability
162
XP patients with the most severe neurologic and somatic abnormalities (truncating mutations in both alleles) and patients with minimal or no neurologic abnormalities (splice-site mutations that permit a small amount of normal mRNA to be made); seen in United States, Europe, and the Middle East and the most common form of XP in Japan
Complementation Group A
163
5 patients in 4 kindreds who had the cutaneous abnormalities characteristic of XP (including neoplasms) in conjunction with neurologic and ocular abnormalities typical of CS
Complementation Group B
164
Patients have XP with skin and ocular involvement but without neurologic abnormalities;most common group in the United States, Europe, and Egypt; typically do not give a history of severe blistering sunburns on minimal sun exposure
Complementation Group C
165
XP patients have been described with several different clinical phenotypes; may have cutaneous XP with late onset of neurologic abnormalities in their second decade of life or XP with no neurologic abnormalities; may have CS, TTD or COFS syndrome with XP
Complementation Group D
166
XP patients found in 1 kindred in Europe and several in Japan; no neurologic involvement
Complementation Group E
167
XP patients have been found mainly in Japan; most patients have mild clinical symptoms without neurologic abnormalities or skin cancer; residual rate of DNA repair is very low (only 10-20% of normal)
Complementation Group F
168
There is a large variation in clinical features among
these XP patients; had clinical features of both XP and severe CS with cachexia and death in the first decade; had no neurologic abnormalities
Complementation Group G
169
Have normal DNA NER but defect in an error-prone, translesional DNA damage bypass polymerase; Have clinical XP with no neurologic abnormalities.
Xeroderma Pigmentosum Variant
170
A very rare, autosomal recessive degenerative dis- ease with cutaneous, ocular, neurologic, and somatic abnormalities characterized by cachectic dwarfism, deafness, and pigmentary retinal degeneration with a characteristic “salt and pepper” appearance of the retina with marked loss of subcutaneous fat, resulting in a “wizened” appearance with typical “bird-headed” facies and prominent “Mickey Mouse” ears
Cockayne syndrome
171
Rare autosomal recessive disorder that is characterized by sulfur deficient, brittle hair and includes a broad spectrum of clinical abnormalities that may include photosensitivity, ichthyosis, intellectual impairment, short stature, microcephaly, characteristic facial features (protruding ears, micrognathia), recurrent
infections, bilateral cataracts, dystrophic nails, and bone abnormalities
Trichothiodystrophy
172
Diagnosis: Trichothidystrophy
Based on examination of hair shafts: display tiger tail banding under polarizing microscopy
173
Rare, autosomal recessive disorder caused by mutations in BLM gene which encodes a RecQ helicase, characterized by growth deficiency, unusual facies, sun-sensitive telangiectatic erythema, immunodeficiency, and predisposition to a variety of different cancers; most frequent among Ashkenazi Jews
Bloom syndrome
174
Diagnosis: Bloom syndrome
Observation of quadriradial chromosomes (0.5-14% of lymphocytes of BS patients)
10-fold increased frequency of spontaneous sister chromatid exchanges
175
Rare, autosomal recessive disorder, caused by a mutation in WRN, which encodes a RecQ helicase, characterized by several features of premature aging including including graying and thinning of hair, loss of subcutaneous fat, wrinkling of skin, type 2 diabetes, osteoporosis and cardiovascular disease secondary to atherosclerosis, and an increased cancer risk with death usually occurs before the age of 50 years due
Werner syndrome
| Adult progeria
176
Hallmark of Rothmund-Thomson syndrome
Poikiloderma with variegated cutaneous pigmentation, atrophy, and telangiectasias beginning in infancy
177
Rare, autosomal recessive disorder with mutations in the helicase RecQL4, characterized by photosensitivity and development of prominent erythema and facial swelling on sun exposure, which may be accompanied by blister formation; have sparse scalp hair, eyebrows, and eyelashes, juvenile cataracts, stunted growth, skeletal abnormalities including radial bone defects, and a pre- disposition for cancer ( osteosarcomas)
Rothmund-Thomson syndrome
178
An autosomal recessive disease characterized by diffuse hyperpigmentation from birth or early childhood accentuated over the neck, joints, and trunk, café-au-lait spots and achromic lesions, progressive pancytopenia, growth retardation, various congenital abnormalities of the heart, kidney, and limbs, and a predisposition to cancer
Fanconi anemia
179
Diagnosis: Fanconi anemia
Western blot: inability of FA cells to ubiquitinate the FANCD2 protein after exposure to DNA cross-linking agents
180
Most common features of Dyskeratosis congenita (triad)
1. Reticulated hyperpigmentation
2. Dystrophic nails
3. Mucosal leukoplakia
181
An X-linked multisystem disease, defect in gene DKC1 encoding dyskerin, with cutaneous, mucosal, ocular, gastrointestinal, and hematologic abnormalities and an increased incidence of cancer
Dyskeratosis congenita
182
Present in all patients of Dyskeratosis congenita
Nail dystrophy
183
Main cause (71%) of early death in Dyskeratosis congenita
Bone marrow failure
184
Beighton Criteria for Joint Hypermobility
1. Passive dorsiflexion of the fifth finger >90'
2. Passive apposition of the thumbs to the flexor aspect of the forearm (Beighton sign)
3. Hyperextension of the elbow >10'
4. Hyperextension of the knees >10'
5. Ability of the palms to completely touch the floor during forward flexion of the trunk with knees fully extended
185
AD with hyperextensible skin, easy bruising, wide, atrophic scars and hypermobile joints
Collagen type V - COL5A1, COL5A2
Classical Ehlers-Danlos syndrome
186
AD/AR with smooth, velvety skin; joint hypermobility
| Collagen type III; tenascin XB - COL3A1; TNXB
Hypermobility type Ehlers-Danlos syndrome
187
AD with thin, translucent skin with easy bruising, arterial and visceral rupture and typical facies
Collagen type III - COL3A1
Vascular type Ehlers-Danlos syndrome
188
AR with atrophic scars, easy bruising, neonatal hypotonia, scoliosis, ocular rupture and Marfanoid habitus
Lysyl hydroxylase - PLOD1
Kyphoscoliosis type Ehlers-Danlos syndrome
189
AD with hyperextensible and fragile skin, severe joint hypermobility and congenital hip dislocation
Collagen type I - COL1A1; COL1A2
Arthrochalasia type Ehlers-Danlos syndrome
190
AR with severely fragile, sagging, redundant skin; hernias and premature rupture of fetal membranes
Procollagen I N-peptidase - ADAMTS2
Dermatosparaxis
191
Presents with asymptomatic, flat-topped yellowish papules and nodules, which, when grouped, form large plaques several centimeters in diameter often on the proximal extremities, truncal which is symmetric and may be more widespread associated with osteopoikilosis, fractures in Buschke-Ollendor syndrome due to LEMD3 (MAN1) mutations; histopathology showing increased elastic tissue
Dermatofibroma lenticularis
192
Presents with asymptomatic, coalescing yellow macules and papules, occasional reticulate or checkered pattern with lax, redundant areas often on neck, axillae, groin, flexural surfaces, and exposed areas associated with older age and exposure to saltpeter fertilizer in Norwegian farmers; histopathology showing fragmented, thickened, mineralized elastic fibers in mid- and deep-reticular dermis
Localized acquired cutaneous Pseudoxanthoma Elasticum
193
Presents with asymptomatic or pruritic, erythematous lesions that progress to hyperpigmented plaques, with central atrophy, a red, scaly border, and peripheral hyperkeratotic papules, sometimes expressing elastotic debris often on periumbilical or breast area associated with multiparity, ascites, abdominal surgery; uremia, and hyperphosphatemia in chronic renal failure; histopathology showing elimination of basophilic, elastotic debris through channels in addition to thickened and mineralized elastic fibers in mid- and deep reticular dermis
Perforating periumbilical Pseudoxanthoma Elasticum
194
With caried presentations; may resemble pseudoxanthoma elasticum, elastosis perforans serpiginosa, cutis laxa, and anetoderma associated with use of D-penicillamine; histopathology showing thickened elastic bundles with prominent lateral protrusions (“bramble-bush”), granulomatous dermal inflammation, infrequent calcification, and transepidermal elimination of elastic fibers
Long-term penicillamine therapy
195
Presents with numerous small, asymptomatic, discrete, white papules often on neck of middle aged to elderly individuals
Actinic damage to neck
196
Presents with asymptomatic, firm, nonfollicular 1-5 mm whitish papules on trunk and upper extremities often on chest, abdomen, shoulders, back, and proximal extremities; histopathology shows loss of elastic tissue in reticular dermis (relative increase in fibrillar component) and fragmentation, with occasional perivascular mixed infiltrate
Papular elastorrhexis
197
AD disorder with cellular defect of abnormal elastic fibers (ELN/FBLN5 - elastin/fibulin); with features of a later onset, primarily cutaneous, hernias, rare vascular complications, and normal life expectancy
Autosomal Dominant Cutis Laxa
198
XLR disorder with cellular defect of copper metabolism (ATP7A - α-polypeptide of Cu2+ transporting ATPase) usually congenital, distal skin laxity, characteristic facies, coarse cry from vocal cord redundancy, brittle hair, mild joint laxity, occipital exostosis, skeletal abnormalities, failure to thrive, diarrhea and GU diverticulae
X-linked Recessive Cutis Laxa
199
AR disorder with cellular defect abnormal protein folding (FBLN5 - Fibulin 5) or severely underdeveloped elastic fibers (FBLN4 - Fibulin 4) usually congenital, severe, with loose hanging redundant skin, early lethality, emphysema, cor pulmonale, hernias, mucosal prolapse, no mental retardation, cardiovascular abnormalities are rare, no hip dislocation, arachnodactyly, vascular anomalies, increased dissection risk, diaphragmatic abnormalities and GI/GU diverticulae
Autosomal Recessive Cutis Laxa I
200
AR disorder with congenital disorder of glycosylation (CDG-II) leading to abnormal pH regulation of Golgi compartments then leading to impaired Golgi trafficking then reduced collagen bundle size and underdeveloped elastic fibers (ATP6V02a - α2 subunit of V-type H+-ATPase with microcephaly, developmental delay, hypotonia, congenital hip dislocation, mental retardation. delayed fontanel closure, progressive neurologic abnormalities, CL improving after puberty and dental carries
Autosomal Recessive Cutis Laxa II (Debre type)
201
AR disorder with abnormal mitochondrial proline metabolism (PYCR1 - Pyrroline-5-carboxylate reductase 1) with progeroid appearance, osteopenia, variable connective tissue weakness, wrinkly lax skin over hands, finger contractures, triangular facies with mandibular hypoplasia causing prognathism, variable mental retardation, and agenesis of corpus callosum
Autosomal Recessive Cutis Laxa with Progeroid features
202
AR disorder with soluble protein present in both skin and osteoblasts interacting with Rab6, which interacts with conserved oligomeric Golgi complex (COG complex) disrupting the Golgi trafficking presents (GORAB - SCYL1-binding protein 1) with progeroid features, malar/mandibular hypoplasia, joint laxity, short stature, dwarfism, normal mental development, osteoporosis thus with frequent fractures especially vertebral, usually progressive
Gerodermia osteodysplastica
203
AR disorder with frayed elastic fibers presents with cutis laxa, significant mental retardation, eye anomalies, dystonia, progeroid features and usually progressive
De Barsy syndrome
204
AR disorder subtype of Cutis Laxa with cardiac anomalies and osteochondrodysplasia
Cantu syndrome
205
AR disorder with (PYCR1 - Pyrroline-5-carboxylate reductase 1 or ATP6V0A2 - α2 subunit of V-type H+- ATPase)
Wrinkly skin syndrome
206
AR disorder with increased TGFβ activity thus with impaired elastic fiber assembly presents with
Latent transforming growth factor binding protein 4 (LTBP4) deficiency
207
AR disorder subtype of Cutis Laxa with GI and GU abnormalities, respiratory dysfunction, early lethality, prematurely aged appearance, distinctive facies, normal mental development, mild cardiovascular lesions and growth delay
Transaldolase deficiency
208
Able to extend the tongue to touch the tip of the nose in EDS
Gorlin's sign
209
Consistent and unifying finding in all forms of EDS
Generalized joint hypermobility
210
Most clinically significant EDS subtype due to risk of arterial or major organ rupture
Vascular type EDS
211
Classic quadrad of Vascular type EDS
1. Characteristic facial appearance (thin nose and upper lip, small earlobes, sunken pigmented periocular regions)
2. Thin, translucent skin with prominent venous pattern
3. Extensive bruising or hematoma
4. Vascular or visceral rupture
212
Most common cause of death in Vascular type EDS
Arterial rupture
213
Most productive approach to the management of EDS
Multidisciplinary preventive strategy
214
Most common finding in EDS of most types present in 3/4s of patients but common in Hypermobility type EDS
Fatigue
215
Defect/Mutation (gene - protein)
| Marfan syndrome
FBN1 - fibrillin 1
| chormosome 15q21.1
216
Angiotensin blocker that blocks TGF-B and decreases phosphorylation of Smad2 independent of its TGF-B effects
Losartan
217
AD generalized connective tissue disorder affected 3 organs: ocular (lens dislocation), skeletal (excessive extremity length, loose joints, anterior chest deformities and kyphoscoliosis), and cardiovascular (aortic aneurysm and MV redundancy)
Marfan syndrome
218
Characteristically dolichostenomelic (tall and thin), with a lower body segment (pubic symphysis to floor) that is longer than the upper segment (height minus lower segment) with the arm span exceeds the person’s height by several centimeters, distal bones are excessively long (arachnodactyly), bone overgrowth and joint laxity
Marfanoid habitus
219
Thoracic cage abnormalities in Marfan syndrome from excessive rib cage overgrowth
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Pectus excavatum (sternal depression)
Pectum carinum (sternal projection)
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220
First sign of Marfan syndrome
Dislocation of the hip
221
The thumb extends well beyond the ulnar border of the hand when overlapped by the fingers
Steinberg (or thumb) sign
222
The thumb overlaps the fifth finger as they grasp the opposite wrist
Walker-Murdoch (or wrist) sign
223
Responsible for the majority of the morbidity and mortality in Marfan patients
Cardiovascular abnormalities
224
Most common cardiovascular defect in Marfan syndrome
Medial necrosis of the aorta --> Diffuse dilatation of the proximal segment of the ascending aorta with aortic regurgitation
225
Administered to prevent aortic dilatation by decreased myocardial contractility used in Marfan syndrome
Propanolol
226
Rare AR multisystem disorder exhibiting progressive calcification of elastic tissue defect presents with the skin changes demonstrating yellowish, flat-topped, discrete, and confluent papules in the skin creases of the sides and nape of the neck, perineum, axillae, umbilicus, and flexural folds with skin redundancy that increases with advancing age ("plucked chicken skin”)
Pseudoxanthoma Elasticum
| Grönblad–Strandberg syndrome
227
Defect/Mutation (gene - protein)
| Pseudoxanthoma Elasticum
ABCC6 - MRP6
| chromosome 16p13.1
228
Most common ophthalmologic finding in Pseudoxanthoma Elasticum which are radial curvilinear extension of gray, brown or reddish discoloration from the optic disc aused by visualization of the choroid through tears in the elastic-rich Bruch’s membrane that develop during 3rd-4th decade
Angioid streaks
229
More common ocular finding in children with Pseudoxanthoma Elasticum which is characteristic irregular retinal epithelial mottling is commonly seen resulting from degenerated elastic tissue
Peau d’orange retinal changes
230
Common and potentially serious complication of Pseudoxanthoma Elasticum
Calcification of degenerated elastic tissue of the internal lamina of blood vessels
231
Sites of early manifestations of the calcification of degenerated elastic tissue, which often presents as acute-onset hemorrhage in the 2nd to 4th decade
Renal vasculature
| GI vasculature
232
Histopathology: Distinctive broken curls of basophilic elastic fibers with routine hematoxylin and eosin or Verhoeff-van Gieson staining
Electron microscopy: calcification in a centripetal pattern within elastic fibers
Pseudoxanthoma Elasticum
233
Calcium deposition on elastic fibers can be easily detected with
von Kossa stain
234
A heterogeneous group of disorders that results from abnormalities in elastic tissue which is characterized by widespread laxity of skin and, some other organs; AD, AR, and X-linked forms exist, with recessive forms the most common
Cutis Laxa
235
Composed of an amorphous elastin component (90% of fibril) surrounded by a microfibrillar sheath based on fibrillin; do not spontaneously assemble
Elastic fibers
236
Presents with inelastic and pendulous skin which is hyperextensible, but does not resume its normal shape after stretching; often described as having a bloodhound-like facial appearance with loose skin of the face, neck, shoulders, and thighs
Cutis Laxa
237
Associated with X-linked Cutis Laxa
Occipital horn syndrome
| Menkes disease
238
Stains for elastic tissue
Verhoeff-van Gieson stain
239
Presents with ill-defined areas of loose skin appear insidiously but progressively with elastolysis involving the head and neck and progressing in a cephalocaudal direction usually preceded by an inflammatory eruption (urticaria, erythema multiforme, eczematous eruption) and usually begins in adulthood; pulmonary involvement presents as emphysema and is the most frequent cause of death
Type I Acquired Cutis Laxa
240
Postinflammatory elastolysis characterized by more localized, well-demarcated, nonpruritic erythematous plaques that extend peripherally and have a hypopigmented center appearing in crops over a period of days to weeks, often in association with fever, malaise, and peripheral eosinophilia; occur at sites of previous inflammation; fatal aortitis
Type II Acquired Cutis Laxa (Marshall syndrome)
241
One of the primary presenting features of hereditary gelsolin amyloidosis (AGel amyloidosis), an AD condition resulting from mutations in gelsolin, an actin modulating protein
Acquired Cutis Laxa
242
Acquired Cutis Laxa may develop after drug exposure to
Penicillin
D-penicillamine
Isoniazid
243
Most commonly AD with defect in procollagen I presents with hyperextensible skin and blue sclerae also with increased fractures, dentinogenesis imperfecta, ligament laxity, triangular facies, short stature, hearing impairment, and wormian bones; with 7 sbutypes ranging from mild to lethal
Osteogenesis Imperfecta
244
AD disorder from loss of function mutations in the LEMD3 (also called MAN1) which antagonize both bone morphogenetic protein (BMP) and TGF-β signaling pathways leading to association of connective tissue nevi that appear as collections of skin-colored to yellow papules or plaques (dermatofibrosis lenticularis disseminata) ost commonly located on the buttocks, proximal trunk, and limbs and osteopoikilosis
Buschke-Ollendorff sydrome
245
Defect/Mutation (gene - protein)
| Lipoid Proteinosis
ECM-1 - ECM protein 1
| chromosome 1q21
246
Most reliable clinical signs for diagnosing Lipoid Proteinosis
Hoarse voice
| Thickened sublingual frenulum
247
Earliest finding in Lipoid Proteinosis
Hoarseness from vocal cord infiltration (occurs at birth)
248
Classical finding in Lipoid Proteinosis of beaded papules along the eyelid margins
Moniliform blepharosis
249
AR disorder presents with hoarse voice and thickened sublingual frenulum, which prevents patients from protruding the tongue, beaded eyelid papules, in ltration of warty papules of the skin around the elbows and extensor forearms, and mild alopecia; increased scarring and photoaging of sun-exposed skin may be seen
Lipoid Proteinosis
250
Inherited disorders of the immune system that result in an increased susceptibility to infection and an increased morbidity and mortality
Primary immunodeficiency diseases
251
Classification of Primary immunodeficiency diseases
1. Antibody deficiencies
2. Cellular deficiencies
3. Combined antibody and cellular deficiencies
4. Disorders of phagocytosis and cell killing
5. Complement defects
