Albinism Chédiak–Higashi syndrome Piebaldism Waardenburg syndrome Nevus depigmentosus Idiopathic Guttate Hypomelanosis Vogt–Koyanagi–Harada syndrome Phenylketonuria (PKU)

1. Causes of Hypomelanosis
CONT.

2. Other causes of Hypomelanosis
1. Albinism
2. Chédiak–Higashi syndrome
3. Piebaldism
4. Waardenburg syndrome
5. Nevus depigmentosus
6. Idiopathic Guttate Hypomelanosis
7. Vogt–Koyanagi–Harada syndrome
8. Phenylketonuria (PKU)

3. Albinism

4. Albinism
• From Latin albus, meaning "white“.
• DEFINITION: group of genetic disorders characterized by diffuse
pigmentary dilution due to a partial or total absence of melanin
pigment within melanocytes of the skin, hair follicles and eyes.
• Mostly autosomal recessive.
• Absence of pigmentation from birth but normal number of
melanocytes are present within the epidermis.
• The international average for albinism is about 1 in 20,000.
• Sunburns, skin cancers are common.

8. An individual can be carriers of genes
for albinism without exhibiting any
traits, albinistic offspring can be
produced by two non-albinistic parents.

11. Types of Albinism
There are two main types of albinism:
A. OCULOCUTANEOUS (OCA):
Affecting the eyes, skin and hair
people with this type of albinism have white or pink hair, skin, and
iris color, as well as vision problems.
Most severe type.
B. OCULAR (OA):
Hypopigmentation involving primarily the retinal pigment
epithelium. person's skin and eye colors are usually in the normal
range.

12. Eye affection in Albinism
1. Translucent or light-colored eyes due to
reduced pigmentation in iris
2. Light sensitivity (photophobia)
3. Reduced visual acuity or functional
blindness
4. Reduced retinal pigmentation
5. Rapid eye movements (nystagmus)
Involuntary eye movements
6. Crossed eyes (strabismus)
7. Hypoplastic foveae
8. Lack of stereopsis /binocular vision

14. OCA1A
• White hair, milky white skin, and blue–gray
eyes at birth.
• Melanocytic nevi amelanotic.
• The hair may develop a slight yellow tint due to
denaturing of hair keratins.
• Extreme sensitivity to UV light and a strong
predisposition to skin cancer.
• Reduced visual acuity is most severe, and some
patients are legally blind.

15. OCA1B
1. “Yellow albinism” dt. the eventual color
of the patient’s hair (the formation of yellow
pheomelanin requires less tyrosinase activity).
2. “Minimal pigment OCA”,
3. “Platinum OCA”
4. “Temperature-sensitive OCA”. The abnormal
tyrosinase enzyme is temperature-sensitive,
losing its activity above 35°C. As a result, melanin
synthesis does not occur in warmer areas of the body
• All of these patients have little or no pigment at birth,
but they develop some pigmentation of the hair and
skin during the first and second decades of life.
• The majority burn without tanning after sun exposure.
• Some degree of iris translucency is often present.
• Amelanotic or pigmented melanocytic nevi can develop.

16. OCA2
• Clinical spectrum is broad, ranging from minimal
to moderate pigmentary dilution of the hair, skin
and iris.
• Little to no ability to tan.
• Pigmented melanocytic nevi and lentigines may
develop in sun-exposed areas.

17. OCA3
• “Rufous” vast majority of OCA3 patients in
individuals with type III–V skin color red–
bronze skin color, ginger-red hair, and blue or
brown irides.
• “Brown” light brown skin, light brown hair and
blue–grey irides.

18. OCA4
• Most common among individuals with albinism who
are from Japan (~25% of patients)
• Hair color ranges from white to yellow–brown.
• Patients may or may not develop increased
pigmentation of the skin and hair over time.

19. OA1
• Substantial reduction in visual acuity.
• Hypopigmentation of the retina.
• Presence of macromelanosomes in the eyes.
• Affected boys have nystagmus, photophobia and foveal hypoplasia.
• Iris hypopigmentation with translucency.
• Their skin is usually clinically normal without notable pigmentary dilution.

20. Treatment of Albinism
• There is no cure for albinism.
• Treatments only ease the symptoms.
• PHOTOPROTECTION: to avoid cutaneous
photocarcinogenesis, in particular the development
of SCC;
1. Large brimmed hat.
2. Wear dark glasses.
3. Always wear sunscreen SPF > 20.
4. Special UV proof clothing/swimsuits.
5. Sun avoidance during peak hours of UV exposure.
• VISUAL REHABILITATION: with longitudinal care as required. Glasses are
often prescribed to correct vision problems and eye position. Eye muscle
surgery is sometimes recommended to correct nystagmus or strabismus.

21. Chédiak–Higashi syndrome
(CHS)

22. CHS
• Rare AR disorder characterized by;
1.OCA with a silvery-gray cast to the hair,
photophobia, nystagmus and ocular
hypopigmentation.
2.An admixture of hyper- and
hypopigmentation may be evident in
chronically sunexposed skin, especially in
patients with relatively dark constitutive
pigmentation.
3.Bleeding diathesis due to diminished function
of platelet dense granules.
4.Progressive neurologic dysfunction.
5. Severe immunodeficiency due to abnormal
lytic granules in lymphocytes, NK cells and
neutrophils ( phagocytosis).
6.Accelerated phase, lymphoma-like-syndrome
usually life-threatening in childhood.

24. CHS
• A hallmark of the disorder is the presence
of giant lysosome-related organelles,
including melanosomes, platelet dense
granules and neutrophil granules.
Examination of a peripheral blood smear for
the latter represents a simple method of
screening for this condition.
• CHS is caused by mutations in the
lysosomal trafficking regulator gene
(LYST), which encodes a cytoplasmic
protein that regulates fission/fusion of
lysosome-related organelles.

26. Treatment of CHS
• There is no specific treatment.
• Bone marrow transplants appear to have been successful in
several patients.
• Infections are treated with antibiotics and abscesses are
surgically drained when appropriate.
• Antiviral drugs such as acyclovir have been tried during the
terminal phase of the disease.
• Cyclophosphamide and prednisone have been tried.
• Vitamin C therapy has improved immune function and clotting in
some patients

27. Piebaldism

28. Piebaldism
• Rare, AD with variable phenotype, presenting at
birth characterized by; poliosis and congenital,
stable, circumscribed areas of leukoderma due to
an absence of melanocytes within involved sites.
• Mutations in the KIT proto-oncogene (encodes a
member of the tyrosine kinase family of
transmembrane receptors). A functioning KIT
receptor is required for the normal development
of melanocytes, both immediately before
melanoblast migration from the neural crest and
postnatally.

30. C/P of Piebaldism
• White forelock (~90%) triangular or
diamond-shaped, and often symmetrical.
The apex can reach the vertex posteriorly,
and the affected area may extend to the root
of nose and include medial third of eyebrows.
• Poliosis of the eyebrows and eyelashes is a
common finding.

32. C/P of Piebaldism
• Leukoderma favors midline & static and
occur on the central anterior trunk, mid
upper arm to wrist, mid-thigh to mid-calf,
and shins classically spare the
posterior midline (hands and feet are
not usually affected) .
• Leukodermic patches are irregular,
well-circumscribed and milk-white.
• Characteristic feature is the presence of
normally pigmented or
hyperpigmented islands within the
areas of lack of pigmentation and on
normal skin.

36. Tx of Piebaldism
• Photoprotection.
• Cosmetic camouflage.
• Autografts of normal skin into amelanotic areas, same techniques used in
vitiligo.

37. Waardenburg syndrome
(WS)

38. WS
• Is a rare autosomal dominant or autosomal recessive disorder that is
characterized by various combinations of the following features:
1. Achromia of the hair, skin or both
in the same pattern as Piebaldism.
2. Congenital deafness.
3. Partial or total heterochromia
irides (including isohypochromia).
4. Medial eyebrow hyperplasia
(synophrys).
5. A broad nasal root.
6. Dystopia canthorum (an increase
in the distance between the inner
canthi, with a normal inter-pupillary
distance).

39. Clinical Classification of WS
Type 1 Dystopia canthorum
Type 2 No dystopia canthorum
Type 3
Type 1 + upper limb abnormalities (e.g. hypoplasia, syndactyly)+
unilateral upper lid ptosis
Type 4 Type 2 + Hirschsprung disease

46. Nevus depigmentosus

47. Nevus depigmentosus
• Pigmentary Mosaicism disorder.
• Usually single hypopigmented patch at any site of body.
• Stable areas of leukoderma are actually hypomelanotic
rather than amelanotic due to block in transfer of
melanosomes from melanocytes to keratinocytes
melanocyte count is overall stable with only a  in melanin.
• Most lesions measure a few centimeters in diameter
and have serrated irregular but well-defined borders,
often breaking apart into smaller macules at periphery.
• Configuration may be geographic, quasidermatomal
distribution or systematized (multiple streaks following the
lines of Blaschko).
• Can be distinguished from a nevus anemicus by diascopy.
• Sporadic occurrence, no medical significance and no
treatment required assurance is sufficient.

50. Nevus depigmentosus: (a) Well demarcated hypopigmented macular
patch on the flank. (b) Non-inflammatory, no dermal pigment (H and E,
×100). (c) Epidermal hypomelanosis (Masson Fontana stain, ×100)

51. Idiopathic Guttate
Hypomelanosis (IGH)

52. IGH
• Very common acquired disorder of unknown cause,
but sun exposure probably plays a role.
• Usually occurs after age 40 seen in up to 80% of
patients over the age of 70 years.
• Occurs in all races and skin types, apparent female
predominance is due to  perception of a cosmetic
problem.
• Lesions occur on the shins and extensor forearms; are
multiple usually small (0.5-8mm), and never occur on
the face or trunk.
• Lesions are irregularly shaped and very sharply
defined smooth porcelain white macules, and are only
of cosmetic significance.
• Once present, they do not change in size or coalesce.
• Rx: Photoprotection / Cryotherapy or dermabrasion.

55. HP of IGH
• Flattening of the dermal–epidermal
junction (most consistent histologic
features).
• Moderate to marked reduction or focal
absence of melanin granules in the basal
and suprabasal layers.
• Basket-weave hyperkeratosis.
• There is a moderate to relatively marked
reduction in the number of DOPA-positive
epidermal melanocytes (10–50%
compared with normal skin), but these
cells are never totally absent.

56. Vogt–Koyanagi–Harada
syndrome (VKHS)

57. VKHS
• Rare multisystemic disease
involving various melanocyte-containing
organs, such as eyes,
meninges, central nervous system,
skin, membranes, mucosa and
inner ear.

58. Etiology of VKHS
• Unknown. An abnormal response to a virus, and immunological
mechanisms, have been postulated.

59. Major features of VKHS

65. C/P of VKHS
• Mainly affects dark-skinned people or white people with dark pigmentation. It is
rare but widely distributed.
• Most cases occur in the third and fourth decades but children may be affected. It
affects the skin, eyes, inner ears and meninges.
• CRITERIA FOR DIAGNOSIS ARE AS FOLLOWS:
1. No history of ocular trauma or surgery preceding the initial onset of
uveitis.
2. No clinical or laboratory evidence suggestive of ocular disease entities.
3. Bilateral ocular involvement: an early sign is diffuse choroiditis; a late
sign is ocular depigmentation.
4. Neurological findings: meningismus, CSF pleocytosis
5. Auditory findings: tinnitus, labyrinthine deafness.
6. Skin and hair changes: alopecia areata, vitiligo, poliosis.
• Typically, this condition is first diagnosed by ophthalmologists as the uveitis starts
the march of symptoms and signs.

66. Histologic examination VKHS
• Amelanotic skin (which often appears after the systemic symptoms)
demonstrates absence of melanocytes + mononuclear infiltrate
consisting primarily of CD4+ lymphocytes, suggesting a prominent role
for cell-mediated immunity i.e. autoimmune disease, with the melanocyte,
tyrosinase or tyrosinase-related protein as targets. Colloid–amyloid bodies
are also found at the dermal–epidermal junction.

67. Phenylketonuria (PKU)

68. PKU
• PKU is an inherited disorder that increases the levels of phenylalanine in
the blood.
• Due to defective hepatic enzyme PHENYLALANINE HYDROXYLASE
(PAH) necessary to metabolize the amino acid phenylalanine ('Phe') to the
amino acid tyrosine.

71. C/P of PKU
• Early diagnosis is essential because symptoms are not
obvious in a newborn infant.
• Mental retardation may develop gradually.
• An early clue to the disease is lighter color of the skin and
hair than unaffected family members, eczema and a
musty odor.
• Delayed mental and social skills.
• Head size significantly below normal (microcephaly).
• Hyperactivity.
• Jerking movements of the arms or legs.
• Seizures.
• Skin rashes.
• Unusual positioning of hands.

73. Dx of PKU
• PKU is normally detected using the HPLC test
• Guthrie test: Devised by Dr. Robert Guthrie (1916 - 1995) after the birth of
his own child with PKU. The test has been widely used throughout North
America and Europe as one of the core newborn screening tests since the
late 1960s.
• In recent years it is gradually being replaced in many areas by newer
techniques such as tandem mass spectrometry that can detect a wider
variety of congenital diseases.

74. Guthrie test
A small drop of blood is taken from the heel of a newborn and applied to a card
A small portion of the dried disc is incubated on a petri dish plated with Bacillus subtilis bacteria in the
presence of a growth inhibitor, B-2-thienyl-alanine.
The presence of high levels of Phe in the blood sample overcomes the inhibition, and allows the
bacteria to grow.

75. Treatment

78. References
• Dr. Angelo Smith M.D WHPL
• Mohammad Jafferany Ajyad general hospital Makkah.
• Bolognia 3rd ed.
• http://www.edoj.org
• http://www.e-ijd.org
• http://www.medscape.com
• Google Images