Disordes Of Hearing And Vision: 100 Syndromes

Front 1

BLEPHAROPHIMOSIS, PTOSIS, and EPICANTHUS INVERSUS (BPES)
Gene, Chromosome, Inheritance

Back 1

VISION

FOXL2 gene
3q23
Autosomal DOMINANT (50% de novo)

Front 2

BLEPHAROPHIMOSIS, PTOSIS, and EPICANTHUS INVERSUS (BPES)
Clincial Features

Back 2

Blepharophimosis, ptosis, epicanthus inversus, and telecanthus.
Type I includes the four major features and premature ovarian failure (POF);
Type II includes only the four major features.

Front 3

BLEPHAROPHIMOSIS, PTOSIS, and EPICANTHUS INVERSUS (BPES)
Molecular testing

Back 3

Combination of seq analysis and deletion testing

Front 4

CONGENITAL HEARING LOSS- Connexin 26 and 30
Gene, Chromosome, Inheritance

Back 4

HEARING
GJB2 (Cx26), GJB6 (Cx30)
13q11-12
Autosomal RECESSIVE

Front 5

CONGENITAL HEARING LOSS- Connexin 26 and 30
Clinical Features

Back 5

Congenital mild-profound SNHL.

Rare patients can have AD Cx26 HL which can include skin findings: palmarplanter keratoderma, KID syndrome

Front 6

CONGENITAL HEARING LOSS- Connexin 26 and 30
Molecular Testing

Back 6

GJB2: sequencing of exon 2 and exon 1 for splice site mutation (4th most common mutation).
35delG common in caucasians,
235delC in Asians, 167delT,
del35Gand Cx30 gene deletion in Ashkenazi Jewish. GJB6-D13S1830 deletion: deletion that includes Cx30, causes HL if homozygous or combined with single Cn26 mutation.

Front 7

HERMANSY-PUDLAK SYNDROME
Gene, Chromosome, Inheritance

Back 7

VISION
HPS1
AP3B1
HPS3,4,5,6,7and 8
HPS 3,4,5,and 6
AUTOSOMAL RECESSIVE

Front 8

HERMANSY-PUDLAK SYNDROME
Clinical Features

Back 8

Oculocutaneous albanism and a bleeding diathesis: hypopigmentation of the skin and the hair, nystagmus, reduced iris pigment, reduced retinal pigment, foveal hypoplasia, increased crossing of optic nerve fibers. Can develop skin cancer, pulmonary fibrosis, colitis

Front 9

HERMANSY-PUDLAK SYNDROME
Molecular Test

Back 9

Del/Dup analysis HPS1 (~75% Puerto Rican HPS), HPS3 (~25% Puerto Rican HPS). Targeted mutation analysis HPS3 (~5% non Puerto Rican HPS)

Front 10

JERVELL and LANGE-NIELSEN SYNDROME
Gene, Chromosome, Inheritance

Back 10

HEARING (KCNQ1 and KCNE1
11p15.5, 21q22.1-q22.2
Autosomal RECESSIVE
(Heterozygotes at risk for AD long QT a.k.a. Romano Ward syndrome)

Front 11

JERVELL and LANGE-NIELSEN SYNDROME
Clinical Features

Back 11

Congenital severe- profound bilateral SNHL and prolonged QT interval.
At risk for arrhythmia, syncope, and sudden death

Front 12

JERVELL and LANGE-NIELSEN SYNDROME
Molecular Test

Back 12

KCNQ1 sequencing (90%), KCNE1 (10%)

Front 13

LEBER HEREDITARY OPTIC NEUROPATHY
Gene, Chomosome, Inheritance

Back 13

VISION
MTND1, MTND4, MTND5, MTND6
Proteins: Complex I subunits of the mitochondrial respiratory chain
Cytogenetic loci: Mitochondrial
Inheritance: Mitochondrial

Front 14

LEBER HEREDITARY OPTIC NEUROPATHY
Clinical Features

Back 14

Blurred or clouded vision progressing to degeneration of the retinal nerve and then optic atrophy.
Fundus: vascular tortuosity of central retinal vessels, circumpapillary telangiectatic macroangiopathy, and swelling of the retinal nerve fibers

Front 15

LEBER HEREDITARY OPTIC NEUROPATHY
Molecular Testing

Back 15

Targeted mutation analysis: G11778A (70% cases), G3460A, T14484C (15%)

Front 16

PENDRED SYNDROME
Gene, Chromosome, Inheritance

Back 16

HEARING
SLC26A4 (PDS)
7q31
Autosomal RECESSIVE

Front 17

PENDRED SYNDROME
Clinical Features

Back 17

Bilateral severe SNHL,
temporal bone abnormalities,
VESTIBULAR abnormalities,
Goiter in 75% though (10% have abnormal thyroid function.)

Front 18

PENDRED SYNDROME
Molecular Testing

Back 18

l236P, T416P, H723R, IVS8+G>A represent 50% of all mutations. SLC26A4 sequencing available.

Front 19

USHER SYNDROME
Gene, Chromosome, Inheritance

Back 19

HEARING ( and RP)
11 genes, majority of cases due to MYO7A, USH2A
11q13.5, 1q41
Autosomal RECESSIVE

Front 20

USHER SYNDROME
Clinical Features

Back 20

Type I congenital profound HL, congenital balance problems,
Retinitis Pigmentosa (RP) onset pre- puberty.
Type II congenital mild-severe HL, normal balance, RP onset in teens-20’s, Type III progressive later onset HL, progressive balance problems, variable onset RP.

Front 21

USHER SYNDROME
Molecular Testing

Back 21

Type I MYO7A sequence analysis (40-50%) Type II USH2A sequencing (65%)

Front 22

WAARDENBURG SYNDROME
Gene, Chromosome, Inheritance

Back 22

HEARING
PAX3
Cytogenetic locus: 2q35
Autosomal DOMINANT

Front 23

WAARDENBURG SYNDROME
Clinical Features

Back 23

WS1: SNHL, heterochromic irides, white forelock, early graying, leukoderma, dystrophia canthorum, neural tube defect.
WS2: WS1 without dystrophia canthorum
WS3: WS1 features and limb hypoplasia or contracture, carpal bone fusion, or syndactyly WS4: WS1 with Hirschprung disease

Front 24

WAARDENBURG SYNDROME
Molecular Testing

Back 24

PAX3 gene sequencing (90% WS1)

Disease Mechanism: Haploinsufficiency.