75: Albinism and Other Genetic Disorders of Pigmentation Flashcards
1
Q
What are the two main subtypes of albinism?
A
- Non-syndromic albinism: Symptoms restricted to impaired melanin biosynthesis, including hypopigmentation of skin and hair, and ocular changes such as reduced iris pigment and impaired visual acuity.
- Syndromic albinism: Includes conditions like Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, and Griscelli syndrome, which have additional non-pigmentary symptoms such as bleeding diathesis and immunodeficiency.
2
Q
What is the overall prevalence of albinism in the population?
A
The overall prevalence of albinism is approximately 1 in 10,000 to 20,000 people, with incidence varying depending on geographic region and ethnicity.
3
Q
What are the characteristics of Oculocutaneous Albinism Type 1A (OCA1A)?
A
- Classic tyrosinase-negative OCA: Complete inability to synthesize melanin in skin, hair, and eyes.
- Phenotype: Characteristic ‘albino’ phenotype with white hair, white skin, and blue eyes.
- Changes with age: No changes as they mature; phenotype remains the same across ethnic groups and ages.
- Hair and iris characteristics: Slight yellow tint of hair due to sun exposure; irides are translucent, pink early in life, changing to gray-blue.
4
Q
What are the features of Oculocutaneous Albinism Type 1B (OCA1B)?
A
- Minimal hair pigment: Retains slight TYR activity with TYR missense mutations.
- Pigmentation changes: Very little or no pigment at birth, developing varying amounts of melanin in the first or second decade of life.
- Hair color: Light yellow, light blond, or golden blond at first, transitioning to dark blond or brown in adolescence and adulthood.
- Irides: Light-tan or brown pigment, sometimes limited to the inner third, with some degree of iris translucency.
5
Q
What are the common symptoms associated with syndromic albinism?
A
Syndromic albinism can include various non-pigmentary symptoms such as:
- Bleeding diathesis
- Lung fibrosis
- Immunodeficiency
These symptoms are associated with conditions like Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, and Griscelli syndrome.
6
Q
A patient presents with white hair, white skin, and blue eyes, with no changes as they mature. What type of albinism is most likely, and what is the underlying genetic mutation?
A
The patient most likely has Oculocutaneous Albinism Type 1A (OCA1A), which is caused by a complete loss of tyrosinase (TYR) activity due to mutations in the TYR gene.
7
Q
A child with OCA1B develops dark blond hair in adolescence. What explains this change in pigmentation?
A
The child retains slight tyrosinase (TYR) activity, allowing for the gradual development of melanin in the hair and skin over time.
8
Q
What are the two main subtypes of albinism and their characteristics?
A
-
Non-syndromic albinism:
- Symptoms restricted to impaired melanin biosynthesis.
- Hypopigmentation of skin and hair.
- Ocular changes such as reduced iris pigment, nystagmus, impaired visual acuity, and foveal hypoplasia.
-
Syndromic albinism:
- Includes conditions like Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, and Griscelli syndrome.
- Associated with various non-pigmentary symptoms, including bleeding diathesis, lung fibrosis, and immunodeficiency.
9
Q
What is the overall prevalence of albinism and how does it vary?
A
The overall prevalence of albinism is approximately 1:10,000 to 20,000 people. The incidence varies depending on geographic region and ethnicity.
10
Q
Describe the characteristics of Oculocutaneous Albinism Type 1A (OCA1A).
A
OCA1A Characteristics:
- Classic tyrosinase-negative OCA.
- Complete inability to synthesize melanin in skin, hair, and eyes.
- Completely lacks TYR activity.
- Characteristic ‘albino’ phenotype: white hair, white skin, and blue eyes.
- No changes as they mature; phenotype is consistent across ethnic groups and ages.
- Slight yellow tint of hair due to sun exposure.
- Irides are translucent, pink early in life, transitioning to gray-blue.
- No pigmented lesions; normal architecture of skin and hair bulb melanocytes.
11
Q
What are the features of Oculocutaneous Albinism Type 1B (OCA1B)?
A
OCA1B Features:
- Minimal hair pigment to skin.
- Retains slight TYR activity; TYR missense mutations.
- Hair pigmentation approaches the normal pigment phenotype.
- Very little or no pigment at birth, developing varying amounts of melanin in the first or second decade of life.
- Hair color transitions from light yellow, light blond, or golden blond at first to dark blond or brown in adolescence and adulthood.
- Irides are light-tan or brown, sometimes limited to the inner third, with some degree of iris translucency.
12
Q
What are the characteristics of Oculocutaneous Albinism Type 1 (OCA1) and its subtypes?
A
OCA1 is characterized by:
- White skin and hair
- Severe visual impairment
- No eumelanogenesis, limited to pheomelanogenesis
- Freckles may develop
- Caused by mutations in the TYR gene, leading to loss of tyrosinase activity.
OCA1A: Complete absence of pigment.
OCA1B: Some pigmentation may be present in extremities, where body temperature is lower.
OCA1MP: Limited to pheomelanogenesis with white skin and hair.
13
Q
What are the phenotypic features of Oculocutaneous Albinism Type 2 (OCA2)?
A
OCA2 is characterized by:
- Creamy-white skin at birth that changes little with time.
- Hair is yellow at birth and may darken over time.
- No generalized skin pigment is present, and no tanning occurs with sun exposure.
- Irides are typically blue-gray or light tan/brown.
- Mutations occur in the OCA2 gene on chromosome 15q, affecting melanosome function and pH regulation.
14
Q
What distinguishes Oculocutaneous Albinism Type 3 (OCA3) from other types?
A
OCA3 is characterized by:
- Rare occurrence and a mild phenotype of OCA.
- Distinctive forms in Africa: Brown OCA (BOCA) and Rufous OCA (ROCA).
- Skin can be brick-red, mahogany, or bronze; hair ranges from deep mahogany to sandy red.
- Visual disturbances such as nystagmus and impaired visual acuity may be present.
- Caused by mutations in the TYRP-1 gene, affecting eumelanogenesis.
15
Q
What are the key features of Oculocutaneous Albinism Type 4 (OCA4)?
A
OCA4 is characterized by:
- Rare occurrence, found in 3% of albino individuals and 27% of Japanese albinos.
- Hair ranges from light-yellow to brown.
- Irides can be blue to red-brown with possible nystagmus.
- Skin shows severe cutaneous hypopigmentation similar to OCA1A.
- Caused by defects in the SLC45A2 gene, affecting melanosome pH and melanogenesis.
16
Q
What are the clinical features of Oculocutaneous Albinism Type 5 (OCA5)?
A
OCA5 is characterized by:
- Golden-colored hair.
- White skin.
- Associated with nystagmus, photophobia, foveal hypoplasia, and impaired visual acuity.
- Caused by mutations in the 4q24 locus.
17
Q
What are the distinguishing features of Oculocutaneous Albinism Type 6 (OCA6)?
A
OCA6 is characterized by:
- Occurs in 3% of European albino populations.
- Phenotype varies, similar to OCA2 and OCA4.
- Hair can be light-brown to platinum blonde.
- Skin shows a lighter complexion with or without tanning ability.
- Individuals may experience mild to moderate visual impairment and some may gain pigmentation later in life.
- Caused by mutations in the SLC24A5 gene.
18
Q
A patient with OCA1TS has pigmented arm and leg hair but white scalp hair. What explains this distribution?
A
The TYR protein in OCA1TS is thermolabile, retaining activity in cooler body regions like the extremities.
19
Q
A patient with OCA2 has pigmented nevi and freckles despite generalized hypopigmentation. What explains this phenomenon?
A
Cutaneous melanocytes in OCA2 retain some ability to synthesize melanin later in life, leading to localized pigmentation.
20
Q
A patient with OCA2 has creamy-white skin and yellow hair at birth. What is the role of the P protein in this condition?
A
The P protein regulates the pH of melanosomes, affecting eumelanin synthesis. Mutations in the OCA2 gene lead to hypopigmentation.
21
Q
A patient with OCA3 has brick-red skin and deep mahogany hair. What gene is implicated in this condition, and what is its role?
A
OCA3 is caused by mutations in the TYRP-1 gene, which is involved in the eumelanogenesis pathway and stabilizes tyrosinase.
22
Q
A Japanese patient with OCA4 shows mild pigmentation recovery as they age. What gene is responsible for this condition?
A
OCA4 is caused by mutations in the SLC45A2 gene, which encodes a melanosomal transporter protein involved in pH control and melanogenesis.
23
Q
A patient with OCA1MP has severe visual impairment and white skin. What type of melanin is produced in this condition?
A
OCA1MP is limited to pheomelanogenesis, with no eumelanin production.
24
Q
What are the clinical features of Oculocutaneous Albinism Type 1 (OCA1) and how do they differ from OCA1MP?
A
OCA1 features include:
- White skin and hair
- Severe visual impairment
- No eumelanogenesis, limited to pheomelanogenesis
- Skin remains white and does not tan
- Develops some freckles
OCA1MP differs by having:
- White skin and hair
- Severe visual impairment similar to OCA1A
- Limited to pheomelanogenesis only, with some freckles developing.
25
How does the phenotype of Oculocutaneous Albinism Type 2 (OCA2) vary among different ethnic groups?
In OCA2:
- **African and African American individuals**:
- Hair: Yellow at birth, may darken over time
- Skin: Creamy-white at birth, changes little with time
- Irides: Blue-gray or light tan/brown
- **White and Asian individuals**:
- Hair: Very lightly pigmented at birth, may darken over time
- Skin: Creamy-white, tanning ability varies
- Irides: Blue-gray or lightly pigmented; translucency correlates with iris pigment development.
26
What are the key characteristics and genetic implications of Oculocutaneous Albinism Type 3 (OCA3)?
OCA3 is characterized by:
- Rare occurrence
- Mild phenotype of OCA
- Distinctive forms in Africa: Brown OCA (BOCA) and Rufous OCA (ROCA)
- Skin: Brick-red, mahogany, or bronze; Hair: Deep mahogany to sandy red
- Visual disturbances: Nystagmus and mild visual acuity impairment
Genetic implications include mutations in the **TYRP-1 gene**, which affect the eumelanogenesis pathway and can disrupt melanin production.
27
What are the clinical features and genetic basis of Oculocutaneous Albinism Type 4 (OCA4)?
OCA4 is characterized by:
- Rare occurrence (3% of albino individuals)
- 27% of Japanese albinos
- Hair: Light-yellow to brown
- Irides: Blue to red-brown, may have nystagmus
- Skin: Severe cutaneous hypopigmentation, indistinguishable from OCA1A to mild diluted pigmentation with some tanning ability
The genetic basis involves a defect in the **SLC45A2 gene**, which affects melanosome pH and melanogenesis.
28
Describe the visual and skin characteristics of Oculocutaneous Albinism Type 5 (OCA5) and its genetic implications.
OCA5 is characterized by:
- Hair: Golden-colored
- Skin: White
- Visual issues: Nystagmus, photophobia, foveal hypoplasia, and impaired visual acuity
The genetic implication is linked to the **4q24 locus**, which is responsible for the observed phenotypic features.
29
What are the phenotypic features of Oculocutaneous Albinism Type 6 (OCA6) and its genetic basis?
OCA6 features include:
- Occurrence in 3% of European albino populations
- Phenotype varies, similar to OCA2 and OCA4
- Hair: Light-brown to platinum blonde
- Skin: Lighter complexion with or without tanning ability
- Visual impairment: Mild to moderate
Genetically, it is associated with the **SLC24A5 gene**, and some individuals may gain pigmentation later in life.
30
What is the role of C10orf11 in Oculocutaneous Albinism Type 7?
C10orf11 is responsible for melanocyte differentiation and is associated with melanocyte migration. It is crucial for the proper development and function of melanocytes, which are responsible for pigment production.
31
What are the primary eye symptoms associated with Oculocutaneous Albinism Type 7?
The primary eye symptoms include:
- Nystagmus
- Iris transillumination
- Extremely sparse pigmentation of the peripheral ocular fundus
- Severe visual impairment, contrasting with relatively mild hypopigmentation of skin and hair.
32
What are the recommended management strategies for individuals with Oculocutaneous Albinism?
Management strategies include:
1. Early diagnosis to initiate appropriate interventions for skin and eye symptoms.
2. Sun protection through protective clothing and sunscreen application.
3. Regular skin checkups for skin cancer, especially in cases of severe hypopigmentation.
4. Early referral to an ophthalmologist for corrective interventions.
5. Use of dark sunglasses to alleviate photophobia.
33
What is the significance of genetic analysis in diagnosing Oculocutaneous Albinism?
Genetic analysis is necessary for definitive diagnosis, as it can identify mutations in known albinism-related genes. It is noted that no mutations have been detected in approximately 20% of affected individuals, indicating the importance of genetic testing in understanding the condition.
34
What are the potential risks associated with albinism in terms of skin health?
Individuals with albinism face increased risks for skin health, including:
35
What are the potential risks associated with albinism in terms of skin health?
Individuals with albinism face increased risks for skin health, including:
- Higher incidence of skin cancers such as squamous cell carcinoma and basal cell carcinoma.
- Controversial incidence rate of melanoma, with a noted increase in risk due to the lack of melanin, which normally helps protect against skin damage.
36
What gene is responsible for OCA6 and what is its role?
OCA6 is caused by mutations in the SLC24A5 gene, which acts as an ion transporter on melanosomal membranes.
37
What gene is responsible for OCA7 and what is its phenotype?
OCA7 is caused by mutations in the C10orf11 gene, which is involved in melanocyte differentiation and migration.
38
What could explain a patient with albinism having no mutations in known albinism-related genes?
Genetic alterations in noncoding regions near albinism-related genes or single nucleotide polymorphisms in regulatory regions may be involved.
39
What preventive measures could have reduced the risk of squamous cell carcinoma in a patient with OCA?
Preventive measures include sun protection (e.g., sunscreen, protective clothing) and regular skin checkups to monitor for skin cancer.
40
What are the key visual symptoms associated with Oculocutaneous Albinism Type 7?
Key visual symptoms of Oculocutaneous Albinism Type 7 include:
- Nystagmus
- Iris transillumination
- Extremely sparse pigmentation of the peripheral ocular fundus
- Severe visual impairment
In contrast, skin symptoms are relatively mild hypopigmentation compared to the significant visual impairment.
41
What is the role of the C10orf11 gene in Oculocutaneous Albinism Type 7?
The C10orf11 gene is responsible for melanocyte differentiation and migration. Its implications include the presence of C10orf11-positive cells (melanoblasts) in the dermis, which migrate from the neural crest, indicating its critical role in the development and function of melanocytes in individuals with OCA7.
42
What are the recommended management strategies for individuals with Oculocutaneous Albinism?
Early diagnosis is crucial for initiating appropriate interventions for skin and eye symptoms. Recommended management strategies include:
1. Sun protection: Wearing protective clothing and applying sunscreen to prevent sunburn and skin changes.
2. Regular skin checkups: Especially for adults with OCA to monitor for skin cancer.
3. Referral to an ophthalmologist: For corrective glasses or surgical interventions for strabismus and nystagmus.
4. Use of dark sunglasses: To alleviate photophobia.
5. Prenatal diagnosis: If pathologic mutations are detected in affected family members.
43
What are the potential social implications faced by individuals with albinism?
Individuals with albinism may face social stigma and discrimination, which can lead to lower socioeconomic status and lack of access to healthcare. These factors contribute to increased mortality rates compared to those without albinism and delayed presentation of symptoms due to inadequate resources and preventive measures.
44
What are the differences in skin pigmentation and visual symptoms between Oculocutaneous Albinism and Ocular Albinism?
Differences include:
| Feature | Oculocutaneous Albinism (OCA) | Ocular Albinism (OA) |
|-----------------------------|--------------------------------|-------------------------------|
| Skin Pigmentation | Significant hypopigmentation | Usually mild hypopigmentation |
| Visual Symptoms | Severe visual impairment | Impaired visual acuity, nystagmus |
| Extraocular Symptoms | Present | Sensorineural deafness, congenital malformations |
OCA typically presents with more pronounced skin and visual symptoms compared to OA, which may have milder skin manifestations and additional systemic symptoms.
45
What are the clinical features of Hermansky-Pudlak Syndrome (HPS)?
The clinical features of HPS include:
- Hypopigmentation in the retinal pigment epithelium and iris
- Nystagmus
- Photophobia
- Impaired visual acuity
- Foveal hypoplasia
- Misrouting of the optic nerve in the chiasm
- Symptoms greatly overlap with those of Oculocutaneous Albinism (OCA).
46
What is the etiology and pathogenesis of Hermansky-Pudlak Syndrome?
The etiology and pathogenesis of HPS include:
- Defective G-protein–coupled receptor 143 gene (GPR143) located on chromosome Xp.22.2.
- Involvement in melanosome biogenesis during melanocyte differentiation.
- Prevalence: 1:60,000 (Danish) and 1:50,000 (U.S.).
- GPR143 regulates melanosome size and number via activation of the microphthalmia-associated transcription factor (MITF).
47
What are the diagnostic criteria for Hermansky-Pudlak Syndrome?
The diagnostic criteria for HPS include:
- Exclusion of the absence of hypopigmentation of skin and hair.
- Genetic analysis of the GPR143 and OCA genes to obtain a definitive diagnosis.
48
What is the management approach for individuals with Hermansky-Pudlak Syndrome?
Management for HPS includes:
1. Early referral to an ophthalmologist for appropriate intervention.
2. Corrective glasses for visual impairment.
3. Dark sunglasses to alleviate photophobia.
4. Surgical correction for strabismus and nystagmus.
5. Regular ophthalmologic examinations.
6. Understanding that visual acuity is usually stable throughout life and nystagmus may improve but is unlikely to disappear.
49
What are the nonpigmentary symptoms associated with Hermansky-Pudlak Syndrome?
Nonpigmentary symptoms associated with HPS include:
- Bleeding diathesis due to platelet storage pool deficiency.
- Accumulation of ceroid in tissues.
- Life-threatening symptoms such as interstitial pneumonia and granulomatous colitis mimicking Crohn disease, especially in HPS1 and HPS4.
50
What is the significance of the absence of platelet dense granules on electron microscopy in a patient with HPS?
The absence of platelet dense granules is a gold standard diagnostic finding for Hermansky-Pudlak Syndrome.
51
What gene is defective in ocular albinism (OA1) and what symptoms does it cause?
OA1 is caused by mutations in the GPR143 gene, which regulates melanosome size and number.
52
What types of Hermansky-Pudlak Syndrome are associated with granulomatous colitis and interstitial pneumonia?
HPS1 and HPS4 are associated with granulomatous colitis and interstitial pneumonia.
53
What are the key clinical features of Hermansky-Pudlak Syndrome that overlap with Oculocutaneous Albinism?
The key clinical features of Hermansky-Pudlak Syndrome that overlap with Oculocutaneous Albinism include:
- Hypopigmentation in the retinal pigment epithelium and iris
- Nystagmus
- Photophobia
- Impaired visual acuity
- Foveal hypoplasia
- Misrouting of the optic nerve in the chiasm.
54
What is the genetic basis of Hermansky-Pudlak Syndrome and its role in melanosome biogenesis?
Hermansky-Pudlak Syndrome is associated with a defect in the G-protein–coupled receptor 143 gene (GPR143) located on chromosome Xp.22.2. This gene is involved in melanosome biogenesis during melanocyte differentiation and regulates the size and number of melanosomes via activation of the microphthalmia-associated transcription factor (MITF), which is crucial for melanocyte differentiation.
55
What are the management strategies for patients with Hermansky-Pudlak Syndrome?
Management strategies for Hermansky-Pudlak Syndrome include:
1. Early referral to an ophthalmologist for appropriate intervention.
2. Corrective glasses for visual impairment.
3. Dark sunglasses to alleviate photophobia.
4. Surgical correction for strabismus and nystagmus.
5. Regular ophthalmologic examinations.
6. Monitoring visual acuity, which is usually stable but may improve gradually until adulthood.
7. Understanding that nystagmus tends to improve as individuals mature, but is unlikely to disappear.
56
What are the life-threatening symptoms associated with HPS1 and HPS4 in Hermansky-Pudlak Syndrome?
HPS1 and HPS4 frequently manifest life-threatening symptoms such as:
- Interstitial pneumonia
- Granulomatous colitis mimicking Crohn disease
- Cardiomyopathy (rarely)
These symptoms highlight the severe complications that can arise in individuals with these specific types of Hermansky-Pudlak Syndrome.
57
How does the prevalence of Hermansky-Pudlak Syndrome vary geographically?
The estimated prevalence of Hermansky-Pudlak Syndrome varies geographically:
- General prevalence: 1:500,000 to 1:1,000,000
- Highest known prevalence: Puerto Rico, where 1 in 1800 persons is affected and 1 in 22 is a carrier.
This variation is significant as it may indicate a higher genetic predisposition in certain populations, necessitating targeted screening and awareness in those regions.
58
What are the three forms of Griscelli syndrome and their associated symptoms?
1. GS1: Hypopigmentation with neurologic abnormalities.
2. GS2: Hypopigmentation accompanied by hematologic immunodeficiency and hematologic abnormalities.
3. GS3: Restricted to hypopigmentation of skin and hair.
59
What is the role of BLOC-1 in Griscelli syndrome?
BLOC-1 is a large complex consisting of at least 9 subunits, including HPS7, HPS8, and HPS9, and is involved in the trafficking of TYR and TYRP-1 in cooperation with AP-1 and AP-3. A deficiency in BLOC-1 leads to prominent hypopigmentation.
60
What are the clinical features associated with GS2 of Griscelli syndrome?
GS2 is associated with recurrent pyogenic infections and uncontrolled T-cell and macrophage activation leading to hemophagocytic syndrome, which is considered the accelerated phase and can be fatal without immunosuppressive treatment or stem cell bone marrow transplantation.
61
What genetic defects are associated with the different forms of Griscelli syndrome?
1. MYO5A (GS1): Binds to actin filaments; defect leads to severe neurologic deterioration.
2. RAB27A (GS2): Connects to melanosomes; defect leads to immunodeficiency and fatal hemophagocytic syndrome.
3. MLPH (GS3): Connects RAB27A and MYO5A, involved in melanosome transport.
62
What is the significance of the presence of large clumps of pigment in the hair shaft in diagnosing Griscelli syndrome?
The presence of large clumps of pigment in the hair shaft is diagnostic for Griscelli syndrome, indicating the underlying genetic defects affecting melanosome transport and pigmentation.
63
What gene is mutated in GS1 and what is its role?
GS1 is caused by mutations in the MYO5A gene, which is associated with neurologic development and function.
64
What molecular complex is defective in HPS2?
HPS2 involves a defect in the AP-3 complex, specifically the β3A subunit encoded by the AP3B1 gene.
65
What gene is mutated in GS2 and what is its role?
GS2 is caused by mutations in the RAB27A gene, which is involved in the release of lytic granules from CD8+ T cells.
66
What molecular complex is affected in HPS1?
HPS1 involves disruption of the BLOC-3 complex, which affects organelle distribution and motility.
67
What are the clinical features associated with GS2 of Griscelli syndrome?
GS2 is associated with:
- Recurrent pyogenic infections.
- Uncontrolled T-cell and macrophage activation leading to hemophagocytic syndrome, considered the 'accelerated phase'.
- Fatal without immunosuppressive treatment or stem cell bone marrow transplantation.
68
What genetic defects are associated with the different forms of Griscelli syndrome?
1. **MYO5A (GS1)**: Binds to actin filaments; defect leads to severe neurologic deterioration.
2. **RAB27A (GS2)**: Connects to melanosomes; defect results in immunodeficiency and uncontrolled T-cell activation, leading to fatal hemophagocytic syndrome.
3. **MLPH (GS3)**: Connects RAB27A and MYO5A, involved in melanosome transport.
69
What is the significance of the presence of large clumps of pigment in the hair shaft in diagnosing Griscelli syndrome?
The presence of large clumps of pigment in the hair shaft is a diagnostic feature of Griscelli syndrome, indicating the underlying genetic defects affecting melanosome transport and pigmentation.
70
What is the inheritance pattern of Chédiak-Higashi syndrome?
Chédiak-Higashi syndrome is inherited in an **autosomal recessive** manner.
71
What are the clinical features of Chédiak-Higashi syndrome?
The clinical features include:
- Various degrees of **hypopigmentation** of skin and eyes.
- **Silvery or metallic colored hair**.
- **Immunodeficiency**.
- **Neurologic findings** such as low IQ scores, cerebellar ataxia, and peripheral neuropathy.
- 90% develop **lymphoproliferative syndrome** which is fatal in the accelerated phase.
72
What is fatal in the accelerated phase?
The condition is fatal in the accelerated phase.
73
What is the only treatment for hematologic and immunologic abnormalities in Chediak-Higashi syndrome?
The only treatment is **hematopoietic stem cell transplantation (HSCT)**.
74
What genetic mutation is associated with Chediak-Higashi syndrome?
The genetic mutation associated with Chediak-Higashi syndrome is in the **LYST gene** located at 1q42.3, which encodes a lysosomal trafficking regulator.
75
What diagnostic finding is characteristic of Chediak-Higashi syndrome?
A characteristic diagnostic finding is the presence of **peroxidase-positive large inclusion bodies** in polymorphonuclear neutrophils and occasionally in lymphocytes.
76
What are the differential diagnoses for Chediak-Higashi syndrome?
Differential diagnoses include:
- **Nonsyndromic Oculocutaneous Albinism (OCA)**: restricted to hypopigmentation and ocular symptoms without immunodeficiency.
- **Hermansky-Pudlak Syndrome (HPS)**: includes neutropenia and immunodeficiency in addition to albinism.
- **Griscelli Syndrome (GS)**: symptoms similar but lacks large inclusion bodies in polymorphonuclear neutrophils.
77
What is the pathogenesis of the finding of large inclusion bodies in neutrophils in Chediak-Higashi syndrome?
Chediak-Higashi syndrome involves lysosome dysfunction due to mutations in the LYST gene, leading to the accumulation of large inclusion bodies.
78
What gene is responsible for the condition in a patient with Chediak-Higashi syndrome who has silvery hair and large granules in neutrophils?
Chediak-Higashi syndrome is caused by mutations in the **LYST gene**, which encodes a lysosomal trafficking regulator.
79
What does the LYST gene encode?
The LYST gene encodes a lysosomal trafficking regulator.
80
What is the significance of early intervention in the management of Chédiak-Higashi syndrome?
Early intervention is crucial for managing hypopigmentation of skin and visual impairment in Chédiak-Higashi syndrome, as it can help alleviate symptoms and improve quality of life.
81
Is there a curative treatment for the neurologic symptoms of Chédiak-Higashi syndrome?
There is no curative treatment for the neurologic symptoms, which require rehabilitation.
82
How does the presence of peroxidase-positive large inclusion bodies in polymorphonuclear neutrophils aid in the diagnosis of Chédiak-Higashi syndrome?
The presence of peroxidase-positive large inclusion bodies is a characteristic diagnostic finding for Chédiak-Higashi syndrome, indicating lysosomal dysfunction and aiding in differentiating it from other conditions with similar symptoms.
83
What are the potential outcomes for patients with Chédiak-Higashi syndrome who do not undergo hematopoietic stem cell transplantation (HSCT)?
Patients with Chédiak-Higashi syndrome who do not undergo HSCT may die within the early part of their first decade of life. However, those with mild symptoms may survive longer, though they may experience debilitating neurologic abnormalities.
84
What are the differential diagnoses to consider when evaluating a patient with hypopigmentation of skin, hair, and eyes?
Differential diagnoses include nonsyndromic Oculocutaneous Albinism (OCA), Hermansky-Pudlak Syndrome (HPS), and Griscelli Syndrome (GS).
85
What are Pudlak Syndrome (HPS) and Griscelli Syndrome (GS)?
These conditions may show hypopigmentation but lack the immunodeficiency and neurologic abnormalities characteristic of Chédiak-Higashi syndrome, which also presents with large inclusion bodies in neutrophils.
86
What are the major clinical features of Piebaldism?
Piebaldism is characterized by:
1. **Multiorgan disorder** affecting skin, eye, CNS, and musculoskeletal systems.
2. **Cutaneous lesions** that are self-healing but may leave scars.
3. **Four stages of lesions:**
- **Stage I (vesiculobullous stage):** Vesicular eruptions, erythema, and eosinophilia.
- **Stage II (verrucous stage):** Verrucous eruptions, particularly on the hands and feet.
- **Stage III (hyperpigmentation stage):** Brown to gray-brown pigmentation with linear patterns.
- **Stage IV:** Further complications may arise, including serious eye and CNS abnormalities.
87
What is the genetic basis of Piebaldism?
Piebaldism is associated with mutations in the **IKBKG gene** located on Xp28. This gene is responsible for the function of nuclear factor κB, which is crucial for cellular responses.
88
What are the genetic implications of Piebaldism?
80% of cases involve a deletion of exons 4 to 10 of IKBKG, leading to loss of function. Cells with aberrant IKBKG are sensitive to proapoptotic stimuli and prone to apoptosis. Eosinophilic infiltration is common, with eosinophilia present in **30% to 60%** of cases.
89
What are the diagnostic criteria for Piebaldism according to Landy and Donnai?
The diagnostic criteria for Piebaldism as per Landy and Donnai (1993) include:
1. **Major criterion:** Presence of cutaneous lesions.
90
What is the major criterion for Piebaldism?
Presence of cutaneous lesions that occur from infancy to adulthood.
91
What are the minor criteria for Piebaldism?
Presence of dental, hair, nail, and retinal abnormalities.
92
How can genetic analysis confirm the diagnosis of Piebaldism?
Genetic analysis of IKBKG can confirm the diagnosis.
93
What are the potential complications associated with Piebaldism?
Complications of Piebaldism can include:
- **Secondary infections** and strong inflammation, particularly in Stage I lesions.
- **Serious eye and CNS abnormalities** that can lead to blindness and death.
- **Scarring** or hair loss due to self-healing lesions.
- **No curative treatment** is available, but routine follow-up is essential for managing extracutaneous lesions.
94
What stage of the disease is characterized by whorled hyperpigmentation along Blaschko lines?
This is Stage III (hyperpigmentation stage) of Incontinentia Pigmenti.
95
What gene is implicated in Incontinentia Pigmenti?
IP is caused by mutations in the IKBKG gene, which affects the function of nuclear factor kB.
96
What are the major clinical features of Piebaldism?
Piebaldism is characterized by:
- **Cutaneous lesions**: Various skin manifestations including erythema, vesicles, hyperkeratotic papules, and hyperpigmentation that can heal with focal hypopigmentation, scarring, or alopecia.
- **Extracutaneous symptoms**: Involvement of the eye, CNS, and musculoskeletal system, leading to serious consequences for vision and overall health.
97
What does management of Piebaldism include?
Management includes:
- Regular follow-up for skin lesions to monitor for complications.
- Topical treatments for secondary infections.
98
What is the purpose of monitoring in the context of complications?
To monitor for complications.
99
What are topical treatments used for?
Topical treatments are used for secondary infections and inflammation.
100
Why is awareness of potential serious impacts important?
Awareness of potential serious impacts on vision and CNS function necessitates early intervention.
101
What are the stages of cutaneous lesions in Piebaldism?
Piebaldism has four stages of cutaneous lesions.
102
Describe Stage I of cutaneous lesions in Piebaldism.
Stage I (vesiculobullous stage): Vesicular/bullous eruptions and erythema. Typically appears within 1 week of birth, often bilateral. Eosinophilia present in 30% to 60% of cases.
103
Describe Stage II of cutaneous lesions in Piebaldism.
Stage II (verrucous stage): Verrucous or lichen planus-like keratotic eruptions, particularly on the hands and feet. Histopathology shows dyskeratotic keratinocytes and hyperkeratosis.
104
Describe Stage III of cutaneous lesions in Piebaldism.
Stage III (hyperpigmentation stage): Brown to gray-brown pigmentation with whorled patterns. Melanophages prominent in the upper dermis, with potential for scarring.
105
Describe Stage IV of cutaneous lesions in Piebaldism.
Stage IV: Not explicitly detailed but involves chronic changes and potential complications.
106
What is the clinical significance of the lesions in Piebaldism?
The clinical significance lies in the self-healing nature of these lesions, but they may leave scars or lead to secondary infections, impacting patient quality of life.
107
What is the genetic basis of Piebaldism?
Piebaldism is caused by mutations in the IKBKG gene located on Xp28, which is crucial for the function of nuclear factor kB.
108
What are the implications for patient prognosis in Piebaldism?
Implications include:
**Inheritance**: X-linked dominant inheritance pattern, affecting males and females differently.
**Clinical outcomes**: Patients with aberrant IKBKG are sensitive to proapoptotic stimuli, leading to increased risk.
109
What is the risk associated with sensitivity to proaptotic stimuli?
Increased risk of complications such as secondary infections and severe eye/CNS abnormalities.
110
What is the prognosis for lesions in Wardenburg syndrome?
While many lesions are self-healing, the potential for serious impacts on vision and life necessitates ongoing management and monitoring.
111
What are the clinical features of Wardenburg syndrome?
Autosomal dominant inheritance.
112
What are common skin manifestations in Wardenburg syndrome?
Congenital white forelock, scattered hypopigmented macules, and a triangular-shaped white patch on the forehead.
113
Where are typical sites of skin manifestations in Wardenburg syndrome?
Forehead, chest, abdomen, and extremities.
114
What do white patches indicate in Wardenburg syndrome?
Complete depigmentation (absence of melanocytes) and are often symmetrical.
115
What do hyperpigmented macules resemble in Wardenburg syndrome?
Café-au-lait spots.
116
What is the shape of the white forelock in Wardenburg syndrome?
Diamond-shaped white forelock occurs in 90% of cases.
117
How does lesion distribution change over time in Wardenburg syndrome?
Lesion distribution remains stable throughout life with intrafamilial variability in severity.
118
What is the etiology of Wardenburg syndrome?
Associated with the KIT gene.
119
Where do melanocytes originate in vertebrate embryos?
From the dorsal portions of the closing neural tube.
120
How do progenitor melanoblasts migrate during development?
They migrate dorsolaterally between mesodermal and ectodermal layers to reach their final destinations, including the skin.
121
What is required for early melanoblast development?
Stem cell factor (SCF) expressed by epidermal keratinocytes and its receptor c-KIT on melanoblasts.
122
What happens when there are mutations in c-KIT?
They lead to failure of melanoblast migration from the neural crest to the skin.
123
Which aspect of the body is more frequently affected in Wardenburg syndrome?
The ventral aspect due to its distance from the neural crest.
124
What mutation can cause piebaldism?
Mutation in SNai2.
125
What can cause piebaldism?
SNAI2
126
How is Waardenburg syndrome diagnosed?
Diagnosis is straightforward and includes:
1. **Complete depigmentation** in the chest, abdomen, and extremities
2. **Characteristic white forelock**
3. **Family history** of the condition
4. **Skin biopsy** showing absence of melanin and melanocytes
5. **Mutation of c-KIT** for definitive diagnosis.
127
What are the differential diagnoses for Waardenburg syndrome?
Differential diagnoses include:
- **Vitiligo**
- **Vogt-Koyanagi-Harada disease**
- **Nevus depigmentosus**
- **Hypomelanosis of Ito**
- **Tuberous sclerosis**
- **Waardenburg syndrome** itself.
128
What is the clinical course and management of Waardenburg syndrome?
- The **distribution, size, and shape** of lesions typically do not change during life.
- **Islands of repigmentation** may develop in the white patch on the forehead after sun exposure.
- Characteristic of **typical piebaldism** but may show progressive depigmentation.
- **Epidermal transplantation** may be considered for management.
129
What explains the finding of hyperpigmented macules within depigmented areas in a patient with piebaldism?
Hyperpigmented macules within depigmented areas are due to islands of melanocytes that remain functional.
130
What is piebaldism?
A patient with piebaldism has a white forelock and symmetrical depigmented patches.
131
What gene mutation is responsible for piebaldism?
Piebaldism is caused by mutations in the KIT gene, which affects melanoblast migration during embryonic development.
132
What are the key clinical features of Waardenburg syndrome?
- **Autosomal dominant** inheritance
- **Congenital white forelock**
- **Scattered hypopigmented macules**
- **Triangular-shaped white patch** on the forehead
- **Typical sites**: forehead, chest, abdomen, and extremities
- **White patches**: complete absence of melanocytes, often symmetrical
- **Hyperpigmented macules** similar to café-au-lait spots
- **Diamond-shaped white forelock** in 90% of cases
- **Distribution** of lesions remains for the entire life of affected individuals
- **Intrafamilial variability** in the degree of lesions is significant
133
How does the etiology of Waardenburg syndrome relate to melanoblast migration?
Waardenburg syndrome is associated with mutations in the **KIT gene**.
## Footnote
Melanocytes originate from the dorsal portions of the closing neural tube in vertebrate embryos.
134
What is the role of progenitor melanoblasts in Waardenburg syndrome?
Progenitor melanoblasts migrate dorsolaterally between mesodermal and ectodermal layers to reach their final destinations, including the skin.
135
What is required for early melanoblast development?
Early melanoblast development requires the presence of **stem cell factor (SCF)** expressed by epidermal keratinocytes and its receptor **c-KIT** on melanoblasts.
136
What happens when there are mutations in c-KIT?
Mutations in **c-KIT** lead to failure of melanoblast migration from the neural crest to the skin, affecting the ventral aspect of the body more frequently than the dorsal aspect.
137
What is more frequent in the body than the dorsal aspect?
Body.
138
What are the differential diagnoses for Waardenburg syndrome?
- **Vitiligo**
- **Vogt-Koyanagi-Harada disease**
- **Nevus depigmentosus**
- **Hypomelanosis of Ito**
- **Tuberous sclerosis**
- **Waardenburg syndrome itself**
139
What is the clinical course and management for individuals with Waardenburg syndrome?
- The **distribution, size, and shape** of the lesions typically do not change during life.
- **Islands of repigmentation** may develop in the white patch on the forehead after sun exposure.
- Characteristic of **typical piebaldism** but with progressive depigmentation.
- **Epidermal transplantation** may be considered for management.
140
What are the clinical features of Waardenburg Syndrome type 1 (WS1)?
- **White forelock** (hair depigmentation)
- **Pigmentary anomalies of the iris**
- **Congenital sensorineural deafness**
- **Dystopia canthorum**
- Depigmented macules or patches, synophrys, broad nasal root, and sometimes nose hypoplasia.
141
What are the major criteria for the diagnosis of Waardenburg Syndrome?
The major criteria for diagnosing Waardenburg Syndrome include:
1. **Characteristic white forelock**
2. **Pigmentary anomalies of the iris**
3. **Congenital sensorineural deafness**
4. **Dystopia canthorum**
5. **Affected first-degree relative**
Diagnosis requires either 2 major criteria or 1 major and 2 minor criteria.
142
What is the genetic basis of Tietz Syndrome?
Tietz Syndrome is caused by specific mutations in the **MITF** gene, specifically **Asn210Lys** and **Arg217del**. These mutations have a dominant-negative effect, leading to a distinct phenotype.
143
What is the dominant-negative effect in Dyschromatosis Symmetrica Hereditaria?
It leads to a distinct phenotype characterized by hypopigmentation and severe hearing loss.
144
What are the clinical features of Dyschromatosis Symmetrica Hereditaria?
Clinical features include:
- **Reticulate acropigmentation of Dohi**
- **Autosomal dominant inheritance**
- **Mixture of hyperpigmented and hypopigmented macules** on dorsal aspects of the extremities
- **Freckle-like macules** on the face
- Typically presents in **infancy or early childhood** with usually no complications.
145
What are the key features of Reticulate Pigment Disorders?
Key features include:
- Involvement of multiple diseases such as:
1. Dyschromatosis symmetrica hereditaria (DSH)
2. Dyschromatosis universalis hereditaria (DUH)
3. Reticulate acropigmentation of Kitamura (RAK)
4. Dowling-Degos disease (DDD)
- These disorders can be genetically differentiated and often have autosomal dominant inheritance patterns.
146
What gene is most likely mutated in patients with WS2?
WS2 is most commonly caused by mutations in the MITF gene.
147
What mutation is responsible for neurological symptoms in patients with DSH?
Neurological symptoms in DSH are caused by the Gly1007Arg mutation in the ADAR1 gene.
148
What gene is mutated in patients with Waardenburg Syndrome Type 1 (WS1)?
WS1 is caused by mutations in the PAX3 gene, which regulates the expression of MITF.
149
What gene mutations are associated with Waardenburg Syndrome Type 4 (WS4)?
WS4 is associated with Hirschsprung disease.
150
What gene mutations are associated with Type 4 (WS4) Hirschsprung disease?
WS4 is associated with mutations in the EDNRB, EDN3, and SOX10 genes.
151
What gene mutation is responsible for Tietz Syndrome?
Tietz Syndrome is caused by specific mutations in the MITF gene, such as Asn210Lys and Arg217del.
152
What gene is mutated in Dyschromatosis Symmetrica Hereditaria (DSH)?
DSH is caused by mutations in the ADAIR1 gene, which encodes an RNA-specific adenosine deaminase.
153
What are the clinical features of Waardenburg Syndrome type 1 (WS1)?
WS1 is characterized by:
- **White forelock** (hair depigmentation)
- **Pigmentary anomalies of the iris**
- **Congenital sensorineural deafness**
- **Dystopia canthorum**
## Footnote
Additional features may include depigmented macules or patches, synophrys, broad nasal root, and nose hypoplasia.
154
How do the clinical features of Waardenburg Syndrome type 2 (WS2) differ from those of type 1 (WS1)?
WS2 clinical features are similar to WS1, except for the absence of:
- **Dystopia canthorum**
- **Facial abnormalities**
## Footnote
This means WS2 presents with white forelock, sensorineural deafness, and pigmentary anomalies of the iris without the additional features seen in WS1.
155
What is the significance of mutations in the MITF gene in Waardenburg Syndrome type 2 (WS2)?
Mutations in the **MITF gene** (89.6% of cases) are significant because:
- MITF is a member of the Myc supergene family of transcription factors.
- It plays a crucial role in **melanogenesis** and the survival of melanocytes.
156
What is the role of MITF in melanogenesis?
MITF plays a crucial role in melanogenesis and the survival of melanocytes.
157
What are the symptoms associated with defects in MITF?
Defects in MITF lead to pigmentary and hearing symptoms associated with Waardenburg Syndrome Type 2.
158
What are the major criteria for diagnosing Waardenburg Syndrome?
The major criteria for diagnosing Waardenburg Syndrome include:
1. **Characteristic white forelock**
2. **Pigmentary anomalies of the iris**
3. **Congenital sensorineural deafness**
4. **Dystopia canthorum**
## Footnote
Diagnosis requires either 2 major criteria or 1 major and 2 minor criteria.
159
What are the clinical features of Tietz Syndrome?
Tietz Syndrome is characterized by:
- Specific mutations in **MITF** (Asn210Lys and Arg217del)
- A **dominant-negative effect**, leading to a distinct phenotype
- **Hypopigmentation** that presents as a diffuse pigmentary phenotype similar to that found in OCA2, not patchy as in WS2
- **Severe hearing loss** is also a common feature.
160
What are the key features of Dyschromatosis Symmetrica Hereditaria (DSH)?
Dyschromatosis Symmetrica Hereditaria (DSH) features include:
- **Reticulate acropigmentation of Dohi**
- **Autosomal dominant inheritance**
- A mixture of **hyperpigmented and hypopigmented macules** on the dorsal aspects of the extremities
- **Freckle-like macules** on the face
- Typically presents in **infancy or early childhood** with usually no complications.
161
What are the characteristic features of Dyschromatosis Universalis Hereditaria?
Dyschromatosis Universalis Hereditaria features include:
- Asymptomatic hypopigmented and hyperpigmented macules
- Irregular size and shape
- Generalized distribution over the trunk and limbs, sometimes face
- Early in life
- Abnormalities of hair and nails may be reported
- Associated with abnormalities of dermal connective tissue.
162
What is associated with Dowling-Degos Disease?
Associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications.
163
Where is Dowling-Degos Disease most commonly reported?
Most commonly reported in East Asia, particularly Japan and China.
164
What is the genetic basis of Dowling-Degos Disease?
Genetic heterogeneity with 4 types: DDD1, DDD2, DDD3, and DDD4.
165
What is DDD1?
Heterozygous mutation in the KRT5 gene on chromosome 12q13.
166
What is DDD2?
Mutation in the POFUT1 gene on chromosome 20q11.
167
What is DDD3?
Mutation on chromosome 17p33.3.
168
What is DDD4?
Mutation in the POGUT1 gene on chromosome 3q13.
169
What roles do POFUT1 and POGUT1 play?
Play important roles in the Notch receptor signaling pathway.
170
What are the clinical features of Reticulate Acropigmentation of Kitamura?
Rare condition with autosomal dominant inheritance and high penetrance.
171
What is a characteristic feature of Reticulate Acropigmentation of Kitamura?
Angulated reticulate hyperpigmentation on the dorsum of the extremity.
172
What skin findings are associated with Reticulate Acropigmentation of Kitamura?
Punctate pits and breaks in the epidermal rete ridge pattern on palms and soles.
173
What is not included in Reticulate Acropigmentation of Kitamura?
Hypopigmented macules are never included.
174
When do symptoms of Reticulate Acropigmentation typically appear?
Symptoms typically appear within the first or second decade of life and continue throughout life.
175
What is the diagnosis process for Dyschromatosis Universalis Hereditaria?
Clinical diagnosis based on the mixture of hypopigmented and hyperpigmented macules all over the body, which is characteristic of the phenotype.
176
What is helpful for the diagnosis of Dyschromatosis Universalis Hereditaria?
Gene analysis is helpful for diagnosis.
177
What are the histological findings in Dowling-Degos Disease?
Thin branch-like patterns.
178
What is a characteristic finding in the histopathology of Dowling-Degos Disease?
Filiform epithelial downgrowth of epidermal rete ridges.
179
What is observed in the histopathology of Dowling-Degos Disease?
Concentration of melanin at the tips of the rete ridges.
180
What histopathologic findings are characteristic of a patient with DUH?
Histopathology shows a pigmented basal layer of the epidermis.
181
What does topathology show?
Topathology shows a pigmented basal layer of the epidermis, pigmented incontinence in the papillary dermis, and melanophages in the upper dermis.
182
What staining technique confirms hypermelanosis in the lower epidermis in a patient with RAK?
Fontana-Masson staining confirms hypermelanosis in the lower epidermis in RAK.
183
What gene mutation is responsible for Reticulate Acropigmentation of Kitamura (RAK)?
RAK is caused by heterozygous mutations in the ADAM10 gene.
184
What genes are implicated in Dowling-Degos Disease (DDD)?
DDD is associated with mutations in the KRT5, POFUT1, and POGULUT1 genes.
185
What are the subtypes of Dyschromatosis Universalis Hereditaria (DUH)?
DUH has three subtypes: DUH1 (autosomal dominant, 6q24.2-q25.2), DUH2 (autosomal recessive, 12q21-q23), and DUH3 (heterozygous mutation in ABCB6 on chromosome 2q35).
186
What histologic features are characteristic of DDD?
Histology shows thin branch-like patterns, filiform epithelial downgrowth of epidermal rete ridges, and melanin concentration at the tips.
187
What are the characteristic features of DUH?
DUH presents with asymptomatic hypopigmented and hyperpigmented macules of irregular size and shape, distributed over the trunk and limbs, sometimes affecting the face.
188
What is the genetic basis of Reticulate Acropigmentation of Kitamura (RAK)?
RAK is associated with heterozygous mutations in the **ADAM10** gene.
189
What are the clinical features of Reticulate Acropigmentation of Kitamura (RAK)?
RAK is characterized by:
- **Reticulate hyperpigmentation** on the dorsum of the extremities.
- **Punctate pits** and breaks in the epidermal rete ridge pattern on palms and soles.
- **Hypopigmented macules** are never included.
## Footnote
It typically appears within the first or second decade of life and continues throughout life.
190
What are the clinical features of Dowling-Degos Disease (DDD)?
DDD is characterized by:
- **Reticulate hyperpigmentation** that is progressive.
- **Small, hyperkeratotic, dark-brown papules**, mainly on flexures and great skin folds.
- **Pitted perioral acneiform scars** and genital/perianal reticulated pigmented lesions.
- No abnormalities of hair or nails.
191
What are the genetic types of Dowling-Degos Disease (DDD)?
DDD has four types based on mutations:
1. **DDD1** - Mutation in the **KRT5** gene on chromosome 12q13.
2. **DDD2** - Mutation in the **POFUT1** gene on chromosome 20q11.
3. **DDD3** - Chromosome 17p33.3.
4. **DDD4** - Mutation in the **POGLUT1** gene on chromosome 3q13.
192
What is the role of POFUT1 and POGLUT1?
POFUT1 and POGLUT1 play important roles in the Notch receptor signaling pathway.
193
What are Reticulate Pigmentary Disorders?
Reticulate Pigmentary Disorders are characterized by a variety of genetic mutations that lead to distinct clinical features.
194
What do the inheritance patterns of Reticulate Pigmentary Disorders include?
The inheritance patterns can vary, including autosomal dominant (AD) and autosomal recessive (AR) forms.
195
Why is understanding inheritance patterns crucial?
Understanding these patterns is crucial for genetic counseling and management of affected individuals.
196
What are some examples of disorders and their associated genes?
| Disorder | Inheritance | Gene(s) |
|---------|-------------|---------|
| Disorder 1 | AD | Gene A |
| Disorder 2 | AR | Gene B |
| Disorder 3 | AD | Gene C |
197
What are the clinical features of different Reticulate Pigmentary Disorders?
The clinical features can include various symptoms and severity, often requiring genetic analysis for accurate diagnosis.
198
What are the key features of specific disorders?
| Disorder | Key Features | Inheritance Type |
|---------|--------------|-----------------|
| Disorder 1 | Feature A, Feature B | AD |
| Disorder 2 | Feature C, Feature D | AR |
| Disorder 3 | Feature E, Feature F | AD |
199
How does the comparison of clinical features assist in diagnosis?
This comparison helps in differential diagnosis and management strategies.
