What's new AAPOS 2008 - The Private Eye Clinic

Orphanet J Rare Dis 2007 Nov; 2(1):43.
This is an excellent review article of OCA, a disorder of melanin biosynthesis. They
note that 1 in 70 people carry a gene for OCA. The prevalence varies worldwide with
OCA2 the most prevalent form. The diagnosis of OCA is based on clinical findings of
hypopigmentation of hair and skin as well as the characteristic ocular features
(congenital nystagmus, iris transillumination, hypopigmentation of RPE, foveal
hypoplasia and misrouting of optic fibers). However, due to clinical overlap between the
OCA subtypes, molecular diagnosis is necessary to establish the gene defect and OCA
subtype. Molecular genetic testing of TYR and OCA2 are available on a clinical basis,
whereas currently analysis of TYRP1 and MATP is on a research basis only. Carrier
detection and prenatal diagnosis is possible when the mutation has been identified in
the family.
Gene Gene Product Chr.
Localization
Size Disease name Prevalence
TYR Tyrosinase (TYR) 11q14.3 65 kb (529aa) OCA1
1:40,000
OCA1A
OCA1B (Yellow alb.)
OCA2
(p gene)
OCA2 15q11.2-q12 345 kb
(838aa)
OCA2 (Brown OCA in
Africans)
1:36,000 (white Europeans
1:3,900-10,000 (Africans)
TYRP1 Tyrosinase-related protein 1
(TYRP1)
9p23 17 kb (536aa) OCA3 (Rufous OCA) Rare (white Europeans, Asians)
1:8,500 (Africans)
MATP
Membrane-associated
transporter protein (MATP)
5p13.3 40 kb (530aa) OCA4 Rare (white Europeans)
1:85,000 (Japanese)
They briefly review Hermansky-Pudlak syndrome with the accumulation of ceroid in
tissues and exhibiting severe immunologic deficiency. They may develop interstitial
lung fibrosis, granulomatous colitis and mild bleeding problems due to a deficiency of
granules in platelets. Whereas Chediak-Higashi syndrome shows increased
susceptibility to bacterial infections, prolonged bleeding time and peripheral neuropathy,
Griscelli syndrome has immune impairment and /or neurological deficit in addition to the
hypopigmentation. The authors recommend sunscreen, as the incidence of skin cancer
may be increased.
Fraser syndrome: A clinical study of 59 cases and evaluation of diagnostic
criteria
Van Haelst MM, Scambler JP, Fraser Syndrome Collaboration Group, Hennekam RC.
Am J Med Genet A 2007; 143(24):3194-203.
This is the largest series to date of 59 patients with Fraser syndrome, an autosomal
recessive congenital malformation syndrome by cryptophthalmos, syndactyly, and
urogenital defects. They compared the existing diagnostic criteria (1986) to the present
data from these patients. The authors suggest an adaptation of the diagnostic criteria
for FS by adding airway tract and urinary tract anomalies as major criteria.
Major Criteria
Syndactyly
Cryptophthalmos spectrum
Urinary tract abnormalities
Ambiguous genitalia
Minor Criteria
Anorectal defects
Dysplastic ears
Skull ossification defects
Umbilical abnormalities
66