123 Syndromes: Name, Gene, & Inheritance Flashcards
1
Q
Deletion on 22q11.2 (3-mB del most common) Gene: TBX1 AD, 93% de novo
A
22q11 Deletion Syndrome
2
Q
JAG1, NOTCH2 AD
A
Alagille Syndrome
3
Q
SCN5A (Pathogenic variants in 22 other genes : ABCC9, CACNA1C, CACNA2D1, CACNB2, FGF12, GPD1L, HCN4, KCND2, KCND3, KCNE5, KCNE3, KCNH2, KCNJ8, PKP2, RANGRF, SCN1B, SCN2B, SCN3B, SCN10A, SEMA3A, SLMAP, and TRPM4, each <1%) AD except KCNE5 - XLR
A
Brugada Syndrome
4
Q
BRAF, MAP2K1, MAP2K2, KRAS AD
A
Cardio-Facio-Cutaneous Syndrome
5
Q
HRAS AD
A
Costello Syndrome
6
Q
ACVRL1, ENG, GDF2, SMAD4 AD
A
Hereditary Hemorrhagic Telangiectasia
7
Q
TBX5, SALL4 (related disorder) AD
A
Hold-Oram Syndrome
8
Q
PTPN11, RAF1, BRAF, MAP2K1 AD
A
Noonan Syndrome w/Multiple Lentigines (NS-ML, formerly known as LEOPARD Syndrome)
9
Q
PTPN11, SOS1, KRAS, RAF1, NRAS, CBL, SHOC2, BRAF, RIT1, SOS2, MAP2K1 AD
A
Noonan Syndrome
10
Q
7q11.23 Deletion Contiguous gene deletion syndrome, ELN in the critical region AD most de novo
A
William Syndrome
11
Q
ATM AR (carriers have increased risk of breast, colon and pancreatic)
A
Ataxia-Telengiectasia
12
Q
BLM AR (1/100 carrier freq in Ashkenazi Jewish)
A
Bloom Syndrome
13
Q
FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG (Fanconi anemia group A, B, C, D2, E, F, and G protein; 16q24.3, Xp22.3, 9q22.3, 3p25.3, 6p22-21, 11p15, and 9p13) FA-D1 - BRCA2 (Breast cancer type 2 susceptibility protein, 13q12.3) BRIP1 (Fanconi anemia group J protein, 17q22) FANCL (E3 ubiquitin-protein ligase FANCL) AR, AD (RAD51), XLR – FA-B
A
Fanconi Anemia
14
Q
FBN2 AD
A
Congenital Contractural Arachnodactyly (Beals Syndrome)
15
Q
COL5A1 and COL5A2 AD
A
EDS Classic Type (Type I and II)
16
Q
Unknown Gene AD
A
EDS Hypermobility Type (Type III)
17
Q
COL3A1 AD
A
EDS Vascular Type (Type IV)
18
Q
PLOD1 AR
A
EDS Kyphoscoliotic Type (Type VI)
19
Q
TGFBR1, TGFBR2, SMAD3, TGFB2 AD
A
Loeys-Dietz Syndrome
20
Q
FBN1 AD
A
Marfan Syndrome
21
Q
GJB6 AD
A
Hidrotic Ectodermal Dysplasia 2
22
Q
EDA, EDAR, EDARADD XL (EDA:95%), AD or AR (5%)
A
Hypohidrotic Ectodermal Dysplasia
23
Q
IKBKG (aka NEMO) XLD (most male fetuses miscarry)
A
Incontinentia Pigmenti
24
Q
TYR (OCA1), OCA2, TRYP1, SLC45A2, GPR143 (Ocular) AR, XLR (GPR143)
A
Oculocutaneous Albinism
25
NROB1 XLR
X-Linked Adrenal Hypoplasia Congenita
26
CYP21A2 AR
21 Hydroxylase Deficiency (CAH)
27
AR XLR
Androgen Insensitivity Syndrome (Testicular Feminization)
28
KAL, FGFR1 XLR, AD
Kallman Syndrome Type 1 and 2
29
XXY
Klinefelter Syndome
30
GNAS Sporadic
McCune-Albright Syndrome
31
HYMAI, PLAGL1 UPD isodisomy chromosome 6, paternal 6q24 duplication, or 6q24 methylation defect
Transient Neonatal Diabetes Mellitus
32
X genes that escape inactivation, SHOX Sporadic
Turner Syndrome
33
FOXL2 AD, 50% de novo
Blepharophimosis, Ptosis & Epicanthus Inversus
34
GJB2 (Cx26), GJB6 (Cx30) AR
Congenital Hearing Loss – Connexin 26 and 30
35
HPS1, AP3B1, HPS3,4,5,6,7and 8, HPS9 AR
Hermansky-Pudlak Syndrome
36
KCNQ1 and KCNE1 AR (Heterozygotes at risk for AD long QT a.k.a. Romano Ward syndrome)
Jervell and Lange-Nielson Syndrome
37
MTND1, MTND4, MTND6 Mitochondrial
Lever Hereditary Optic Neuropathy
38
SLC26A4 most common, FOX11, KCNJ10 in rare cases AR
Pendred Syndrome
39
MYO7A, USH2A + multiple other genes AR
Usher Syndrome
40
PAX3 AD
Waardenburg Syndrome
41
HMBS AD
Acute Intermittent Porphyria
42
HBA1, HBA2 AR - If parents Alpha Thal trait, risk for HbH disease if one parent’s mutations are in cis, at risk for HB Bart if both parents in cis
Alpha Thalassemia
43
HBB AR
Beta-Thalassemia
44
F5 AD (moderately inc. risk VTE) AR (significantly inc .risk VTE)
Factor V Leiden Thombophilia
45
F8 XLR
Hemophilia A
46
F9 XLR
Hemophilia B
47
HFE AR (penetrance is low, a large fraction of homozygotes never develop symptoms).
HFE-Associated Hereditary Hemochromatosis
48
BTK XLR
X-Linked Agammaglobulinemia (Bruton’s Agammaglobulinemia)
49
MEFV AR
Familial Mediterranean Fever
50
FGD1 XLR (some AR, AD cases reported)
Aarskog Syndrome
51
POR AR
Antley-Bixler Syndrome
52
BBS1, BBS10 AR (though 10% BBS thought to be tri-allelic)
Bardet-Biedl Syndrome
53
EYA1, SIX1, SIX5 AD
Branchi-Oto-Renal Snydrome
54
CHD7 AD
CHARGE Syndrome
55
RPS6KA3 XLD
Coffin-Lowry Syndrome
56
NIPBL, SMC1A, SMC3, HDAC8, RAD21 AD (NIPBL and SMC3) XLR (SMC1L1)
Cornelia de Lange Syndrome
57
5p Minus Syndrome RPS14?, microRNA 145 and 146a? 12% due to unequal segregation of a translocation or recombination involving a pericentric inversion in one of the parents, 85% sporadic de novo deletions (80% are on the paternal chromosome)
Cri-Du-Chat
58
Unknown AR
Fryns Syndrome
59
GLI3 AD
Greig Cephalipolysyndactyly
60
NPHP1, AHI1, CEP290, TMEM67 and others (19 genes) AR (19 genes with rare-4% prevalence)
Joubert Syndrome
61
KMT2D (66%), KDM6A AD, XLD
Kabuki Syndrome
62
Unknown
Monosomy 1p36
63
Paternally expressed genes within the imprinted locus on 15q11-13 (SNURF-SNRPN, MKRN3, MAGEL2, and NDN) Autosomal, expressed from paternal Ch 15 3-5 Mb deletion of 15q11.2-q13 (~70%), matUPD (15%), PWS imprinting center defect (1-2%)
Prader-Willi Syndrome
64
CREBBP, EP300 AD
Rubenstein-Taybi Syndrome
65
RAI1 17p11.2 deletion (~90%) RAI1 sequencing (5-10%) AD (sporadic unless secondary to a parental balanced translocation)
Smith-Magenis Syndrome
66
69,XXY\>69,XXX (69,XYY very rare) Sporadic without inc risk of recurrence
Triploidy
67
75% are due to maternal nondysjunction 20% to a translocation 5% to mosaicism.
Trisomy 13, Patau Syndrome
68
Less than 1% due to a translocation Maternal nondysjunction (90%), mosaicism (10%)
Trisomy 18, Edwards Syndrome
69
90% due to maternal meiosis nondisjunction (3⁄4 MI error, 1⁄4 MII error)
Trisomy 21, Down Syndrome
70
unknown (HOXD13 21 bp deletions: 1 case report), FGF8?, PTF1A? Isolated inheritance
VACTERL (VATER) Syndrome
71
4p deletion Critical region includes two genes, WHSC1 and WHSC2 of unknown significance 87% de novo, 13% due to unbalanced translocation from a balanced parent
Wolf-Hirschorn Syndrome
72
ABCD1 XLR
X-Linked Adrenoleukodystrophy
73
PSEN1, APP, PSEN2 AD
Early Onset Familial Alzheimer Disease
74
UBE3A 4-6 Mb del (65-75%) UBE3A mutation (11%) Imprinting defect (2.5%) Unbal chrom transloc (\<1%) Pat UPD 15 (\<1%) Del of imprinting center (0.5%)
Angelman Syndrome
75
NOTCH3 AD
CADASIL
76
ASPA AR
Canavan Disease
77
IKBKAP AR
Familial Dysautonomia
78
FMR1 X-linked Triple Repeat, CGG
Fragile X
79
HD AD
Huntington Disease
80
GALC AR
Krabbe Disease
81
NF1 AD
Neurofibromatosis Type I
82
Multiple, main gene PARK2 AD, AR, multifactorial
Parkinson Disease
83
MECP2 XLD
Rett Syndrome
84
ATP7B AR
Wilson Disease
85
SOD1 (rare: SETX, VAPB, BSCL2, VCP, ALS2, SPG20, others) AD (AR ALS2 and SPG20)
Amyotrophic Lateral Sclerosis
86
CMT1: Abnormal myelin, AD, 50% of all CMT, PMP22 (17p11.2), MPZ (1q22), LITAF (16p13.1-p12.3), EGR2 (10q21.1-q22.1), NEFL (8p21) CMT2: Axonopathy, AD, 20-40% of all CMT, KIF1B and MFN2 (1p36.2), RAB7 (3q21), LMNA (1q21.2), GARS (7p15), NEFL (8p21), HSPB1 (7q), MPZ (1q22), GDAP1 (8q12-q21.1) CMT Intermediate Form: Combination of myelinopathy and axonopathy, AD, rare cause of CMT, DNM2 (19p12-p13.2), YARS (1p34-p35) CMT 4: Either myelinopathy or axonopathy, AR, rare cause of CMT, GDAP1 (8q13-q21.1), MTMR2 (11q22), CMT4B2 (11p15), SH3TC2 (5q32), NDRG1 (8q24.3), EGR2 (10q21.1-q22.1), PRX (19q13.1- q13.2 CMTX: Axonopathy with secondary myelin changes, XLD, 10-20% of all CMT, GJB1 (Xq13.1).
Charcot Marie Tooth Disease
87
DMD XLR
Duchenne and Becker Muscular Dystrophy
88
FRDA AR
Friedrich Ataxia
89
PMP22 AD
Hereditary Neuropathy with Liability to Pressure Palsies
90
CAPN3, FKRP, LMNA, SGCA, SGCB, SGCD, SGCG, DYSF Most AR, some AD
Limb-Girdle Muscular Dystrophy
91
DMPK AD
Myotonic Dystrophy Type 1
92
ACTA1, NEB, TNNT1, TPM2, TPM3 RARE: CFL2, KBTBD13, KHLH40, KHLH41 AR or AD
Nemaline MyopathySpinal Muscular Atrophy
93
(Fukuyama (FCMD), Muscle‐Eye‐Brain (MEB), Walker‐Warburg (WWS), Congenital Muscular Dystrophy Type 1D (MDC1D) Responsible gene (protein, cytogenetic locus): FCMD; FCMD (Fukutin, 9q31); MEB: POMGNT1 (protein O‐ mannosidase beta‐1,2‐N‐acetylglucosaminyltransferase, 1p34‐p33); WWS: POMT1 and POMT2 (Protein O‐ mannosyltransferase 1 and 2, 9q34.1, and 14q24.3); MDC1D (LARGE, glycosyltransferase‐like protein LARGE, 22q12.3‐q13.1
Syndromic Congenital Muscular Dystrophy
94
HEXA Follow enzyme testing with DNA testing (some with a positive enzyme assay have a pseudodeficiency allele that does not cause Tay Sachs). HEXA 6 common mutation panel: 92% of Ashkenazi Jewish AR
Tay-Sachs Disease
95
BRCA1 and BRCA2 AD
BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer
96
APC AD (15-30% new mutation)
Familial Adenomatous Polyposis
97
MLH1 (3p21.3, DNA mismatch repair protein MLH1) MSH2 (2p22-p21, DNA mismatch repair protein Msh2) MSH6 (2p16, DNA mismatch repair protein MSH6) PMS2 (7p22, PMS1 protein homolog 2) AD
Hereditary Non-Polyposis Colon Cancer (Lynch Syndrome)
98
TP53 AD
Li-Fraumeni Syndrome
99
MEN1 AD
MEN Type 1 (Multiple Endocrine Neoplasia Type 1)
100
RET Exon 10 and 11 (95% MEN2A), Exon 16 (95% MEN2B) AD
MEN Type 2
101
NF2 AD
Neurofibromatosis Type 2
102
PTEN AD
PTEN Hamartoma Tumor Syndrome
103
TSC1 and TSC2 AD (2/3 de novo)
Tuberous Sclerosis Complex
104
VHL AD
Von Hippel-Lindau Syndrome
105
XPA, XPC, ERCC2, POLH AR
Xeroderma Pgimentosum
106
Imprinting of 11p15.5 CDKN1C, H19, KCNQ1OT1 AD (15%)
Beckwith-Wiedemann Syndrome
107
NSD1 5q35 microdeletion including NSD1: ~15% (70% in Japanese). NSD1 sequencing: 27-93% (12% in Japanese) AD
Sotos Syndrome
108
APTX, SETX AR
Ataxia with Oculomotor Apraxia Type 1 and Type 2
109
ERCC6 (75%), ERCC8 (25%) AR
Cockayne Syndrome
110
LMNA AD (all de novo, paternal age effect)
Hutchinson-Gilford Progeria Syndrome
111
SERPINA1 AR
Alpha-1-Antitrypsin Deficiency
112
CFTR AR
CFTR-Related Disorders
113
XL: COL4A5 (80-100%) AR: COL4A3 and COL4A4 AD: COL4A3 and COL4A4
Alport Syndrome and Thin BM Nephropathy
114
PKD1, PKD2 and PKHD1 AD (PKD1, PKD2) AR (PKHD1)
Polycystic Kidney Disease
115
FGFR3 98% FGFR3 G1138A; ~1% FGFR3 G1138C AD, 80% de novo
Achondroplasia
116
RUNX2 Microdeletions (60-70%) AD
Cleidocranial Dysplasia
117
SLC26A2 AR
Diastrophic Dysplasia
118
FGFR1, FGFR2, FGFR3
FGFR-Related Craniosynostosis
119
EXT1, EXT2 AD
Hereditary Multiple Osteochondromas Syndrome
120
FGFR3 N540K (C1620A) (49%) N540K (C1620G) (21%). Exon 9, 10, 13, or 15 sequencing (80%) AD
Hypochondroplasia
121
COL1A1 and COL1A2 AD and rare AR
Osteogenesis Imperfecta
122
TWIST1 AD
Saethre-Chotzen Syndrome
123
SMN1, SMN2 AR
Spinal Muscular Atrophy
124
CAG Triplet Repeats
Huntington Disease
125
Kayser-Fleisher ring
Wilson Disease
126
GAA Triplet Repeat
Friedrich Ataxia
127
FGFR1 sequencing
5% Pfeiffer 1
128
FGFR2 sequencing
100% Crouzon, Jackson- Weiss, Apert, Pfeiffer 2 and 3, and FGFR2-related isolated coronal synostosis
129
FGFR3 sequencing
100% Crouzon with Acanthosis Nigricans
130
FGFR3 targeted mutation analysis
100% Muenke
131
PAFAH1B1
Miller-Dieker
132
Heterozygous deletion of chromosome 22q13.3 with involvement of at least part of SHANK3
Phelan-McDermid Syndrome
133
STK11 AD
Peutz-Jeghers syndrome
134
FGFR3 pathogenic variant c.749C\>G (p.Pro250Arg)
Muenke Syndrome
135
SALL1
Townes-Brocks Syndrome
136
TCOF1 - AD: 63-93% POLR1D - AD/AR: 6% POLR1C - AR: 1.2%
Treacher-Collins Syndrome
137
NBN AR
Nijmegen Breakage Disorder
138
ZEB2 (also known as ZFHX1B or SIP-1)
Mowat Wilson
