13 - 75 - ALBINISM AND OTHER GENETIC ORDERS OF PIGMENTATION Flashcards
pattern of inheritance of Oculocutaneous albinism
autosomal recessive inheritance
of the 7 subtypes of OCA, which doesn’t have an identified gene yet?
OCA5
ocular albinism pattern of inheritance
X-linked
most common type of albinism in non-Hispanic white, Chinese, and Japanese patients
OCULOCUTANEOUS ALBINISM TYPE 1/ OCA1
classic tyrosinase-negative OCA, there is a complete inability to synthesize melanin in skin, hair, and eyes, resulting in the characteristic “albino” phenotype
OCA1A
- Affected individuals are born with white hair, white skin, and blue eyes, and there are no changes as they mature.
- The phenotype is the same in all ethnic groups and at all ages
- he hair may develop a slight yellow tint as a consequence of the denaturing of the hair protein from sun exposure and/or shampoo use.
- this phenotype of OCA can range from minimal hair pigment to skin and hair pigmentation approaching the normal pigment phenotype.
- Most individuals with OCA1B have very little or no pigment at birth, and develop varying amounts of melanin in the hair and skin in the first or second decade of life.
- In some cases, the melanin develops within the first year.
- The hair color changes to light yellow, light blond, or golden blond at first, as a result of residual pheomelanin synthesis, and eventually can turn dark blond or brown in adolescence and adulthood.
OCA1B
- Pigmentation is found on the **extremities where body temperature is relatively low. **
- In this variation, scalp and axillary hair remain white or slightly yellow, but a**rm and leg hair becomes pigmented. **
- The skin remains white and does not tan
variation of OCA1B, temperature-sensitive phenotype (OCA1TS)
has no eumelanogenesis but is limited to just pheomelanogenesis
OCA1 minimal pigment/ OCA1MP
- Individuals with OCA1MP show white skin and hair and severe visual impairment, resembling OCA1A, but they do develop some freckles.
protein and gene mutated in OCA1
loss-of-function of the melanocytic enzyme tyrosinase resulting from mutation of the TYR gene
gene mutated in OCA2
OCA2
gene mutated in OCA3
TYRP-1
genetic disorder characterized by decreased pigmentation of the eyes and visual disturbances
Ocular albinism (OA)
rare autosomal recessive genetic disorder characterized by hypopigmentation of skin, hair, and eyes accompanied by nonpigmentary symptoms, including bleeding diathesis, caused by platelet storage pool deficiency and **accumulation of ceroid **in tissues
Hermansky-Pudlak syndrome (HPS)
pattern of inheritance of Hermansky-Pudlak syndrome (HPS)
AR
form of Hermansky-Pudlak syndrome (HPS) frequently associated with life-threatening symptoms such as interstitial pneumonia or granulomatous colitis mimicking Crohn disease in affected individuals older than age 30 years
HPS1 and HPS4
form of Hermansky-Pudlak syndrome (HPS) associated with immunodeficiency and uncontrolled lymphocyte and macrophage activation, leading to subsequent hemophagocytic syndrome
HPS2 and HPS10
how many forms of Hermansky-Pudlak syndrome (HPS) have been identified as of this writing?
10
gold standard diagnostic finding in Hermansky-Pudlak syndrome (HPS)
By electron microscopy, platelets from individuals with HPS do not contain dense granules
pattern of inheritence of Griscelli Syndrome
autosomal recessive
rare autosomal recessive genetic disorder characterized by hypopigmentation of skin and hair, with large clumps of pigment in the hair shaft on light microscopy
Griscelli syndrome
how many forms of Griscelli syndrome (GS) have been identified?
3
form of Griscelli syndrome (GS) characterized by hypopigmentation with neurologic abnormalities
GS1
- GS1 is associated with severe developmental delay and mental retardation
form of Griscelli syndrome that is restricted to hypopigmentation.
GS3
- GS3 is restricted to hypopigmentation of skin and hair.
form of Griscelli syndrome (GS) characterized by hypopigmentation accompanied by hematologic immunodeficiency and hematologic abnormalities
GS2
- GS2 is associated with recurrent pyogenic infections and uncontrolled T-cell and macrophage activation leading to hemophagocytic syndrome, the so-called accelerated phase, which can be fatal without immunosuppressive treatment or stem cell bone marrow transplantation.
genes responsible for the 3 GS types
- MYO5A (GS1)
- RAB27A (GS2),
- MLPH (GS3)
he only method to cure the hematologic and immunologic abnormalities in Griscelli syndrome (GS)
Stem cell bone marrow transplantation
pattern of inheritance of Chediak-Higashi Syndrome
autosomal recessive
rare genetic disease with autosomal recessive inheritance characterized by reduced pigmentation of skin and eyes, silvery or metallic colored hair, and neurologic and hematologic disorders
Chédiak-Higashi syndrome
- Neurologic findings, including low IQ scores, cerebellar ataxia, and peripheral neuropathy, appear in childhood or adolescence and tend to progress gradually.
Approximately how many % of individuals with ChédiakHigashi syndrome develop lymphoproliferative syndrome, the “accelerated phase” of the disease that tends to be fatal?
90%
only treatment for hematologic and immunologic abnormalities in Chédiak-Higashi syndrome
Hematopoietic stem cell transplantation
diagnostic finding in Chédiak-Higashi syndrome
Large granules in polymorphonuclear neutrophils on blood smear are diagnostic, and pigment clumping on the hair shaft is also seen.
gene responsible for Chédiak-Higashi syndrome
LYST
characteristic finding in Chédiak-Higashi syndrome
Peroxidase-positive large inclusion bodies are seen in polymorphonuclear neutrophils and, occasionally, in lymphocytes, which is a characteristic finding in CHS
pattern of inheritance of incontinentia pigmenti
XLD
possible organs involved in incontinentia pigmenti
eye, CNS or musculoskeletal
responsible gene for incontinentia pigmenti
IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma)
patern of inheritance of piebaldism
autosomal dominant
stages of incontinentia pigmenti
Stage I (vesiculobullous stage)
* vesicular/bullous eruptions and erythema distributed in a linear or whorled pattern on the trunk and extremities (the face is usually spared)
* appear within 1 week of birth
* The eruption tends to be bilateral but can be unilateral
* Eosinophilia is seen in approximately 30% to 60% of the cases
* eosinophilic infiltration in the lesional skin is a characteristic histologic finding
Stage II (verrucous stage) f
* verrucous or lichen planus-like keratotic eruptions on the extremities, particularly the dorsal hand and foot
* the distribution of lesions does not necessarily correspond to that of the stage I eruption.
* dyskeratotic keratinocytes, hyperkeratosis, and acanthosis
* asts for a **few months and occasionally, may last up to a few years **
Stage III (hyperpigmentation stage)
* appear when individuals are 12 to 16 weeks old,
* brown to graybrown pigmentation distributed in whorled or linear patterns, respecting the Blaschko line.
* Melanophages are prominent in the upper dermis histologically
* The pigmentation disappears almost completely by 4 or 5 years of age and may leave focal hypopigmentation, atrophic scar, or alopecia
Stage IV (hypopigmentation stage)
rare genetic disorder with congenital white patches on the forehead, chest, abdomen, and extremities that result from impairment of melanoblast migration in embryonal development
Piebaldism
Piebaldism results from mutations of what gene?
c-KIT
cause failure of melanoblast migration from the neural crest to the skin.
A diamond-shaped white forelock is present in how many % of affected individuals with piebaldism?
90%
are genetic diseases with congenital pigment disorder plus sensorineural deafness.
Waardenburg and Tietz syndromes
pattern of inheritance of Waardenburg and Tietz syndromes
AD
Identify the subtype of Waardenburg Syndrome
White forelock, heterochromia irides, dystopia canthorum
WS1
Depigmented macules or patches, synophrys, broad nasal root, and nose hypoplasia are sometimes accompanying symptoms.
Identify the subtype of Waardenburg Syndrome
White forelock, heterochromia irides
*no dystopia canthorum**
WS2
Identify the subtype of Waardenburg Syndrome
White forelock, heterochromia irides, dystopia canthorum , plus axial and limb musculoskeletal anomalies
WS3
Identify the subtype of Waardenburg Syndrome
White forelock, heterochromia irides, dystopia canthorum , plus Hirschsprung disease (neonatal intestinal obstruction, megacolon)
WS4
gene mutated in Waardenburg Syndrome 1 and 3
PAX3
encodes a transcription factor regulating expression of MITF
kind of variation of Waardenburg syndrome with a diffuse pigmentary phenotype plus severe hearing loss.
Tietz syndrome
major criteria of Waardenburg Syndrome
- Characteristic white forelock
- Pigmentary anomalies of the iris
- Congenital sensorineural deafness
- Dystopia canthorum
- An affected first-degree relative
Tietz syndrome is caused by specific mutations of what?
MITF—Asn210Lys and Arg217del
RETICULATE PIGMENT DISORDERS
- dyschromatosis symmetrica hereditaria (DSH),
- dyschromatosis universalis hereditaria (DUH),
- reticulate acropigmentation of Kitamura (RAK),
- Dowling-Degos disease (DDD)
- autosomal dominant disease characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal aspects of the extremities, and freckle-like macules on the face.
- skin lesions usually appear in infancy or early childhood.
DYSCHROMATOSIS SYMMETRICA HEREDITARIA
A mixture of hyperpigmented and hypopigmented macules distributed only on the dorsal aspects of the extremities, not on the body
DYSCHROMATOSIS SYMMETRICA HEREDITARIA
mutation present in DYSCHROMATOSIS SYMMETRICA HEREDITARIA
Identification of a pathologic mutation in ADAR1 makes a definite diagnosis
asymptomatic hypopigmented and hyperpigmented macules of irregular size and shape in a generalized distribution over the trunk and limbs, and sometimes the face.
DYSCHROMATOSIS UNIVERSALIS HEREDITARIA
- characterized by angulate reticulate hyperpigmentation of the dorsum of the extremity
- palms and soles contain punctate pits and breaks in the epidermal rete ridge pattern
- Hypopigmented macules are never included in the lesions
- The phenotype appears within the first or second decade of life, and continues throughout life.
RETICULATE ACROPIGMENTATION OF KITAMURA
- rare genetic pigmentary disorder that usually shows an autosomal dominant pattern of inheritance with high penetrance
mutation seen in RETICULATE ACROPIGMENTATION OF KITAMURA
ADAM10
- Small, hyperkeratotic, dark-brown papules that affect mainly the flexures and great skin folds appear after puberty.
- Pitted perioral acneiform scars and genital and perianal reticulated pigmented lesions also have been described.
- Patients usually show no abnormalities of the hair or nails
DOWLINGDEGOS DISEASE
