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100 syndromes - Dina

Terms in this set (124)

acute intermittent porphyria
AD
clinical features- onset after puberty, acute attacks, abdominal pain, muscle weakness, neuropathy, hysteria, anxiety, hepatocellular carcinoma, NO CUTANEOUS FINDINGS
testing- increased urine delta-amonoelevulinic acid (ALA) and porphobilinogen (PBG)during acute attack
Alpha thalassemia
HBA1, HBA2
AR; -a/aa silent carrier, -a/-a (at risk for HBH disease when combined with —/aa), —/aa (at risk for HB Bart's)
clinical features- Hb Bart- loss of all 4 alpha alleles, hydrous fettles, sever hypochromic anemia, death in neonatal period; HbH disease- loss or dysfunction of 3 or 4 alpha alleles, microcytic hypo chromic hemolytic anemia, jaundice
Trait- low MCV- do Hb elect, molecular testing for common mutations (deletions)
Beta thalassemia
HBB
AR
clinical features- severe anemia, severe FTT, at risk populations- Indian, Thai, Middle east, mediterranean, Chinese, African
carriers- low MCV, do Hb elec (reduced HbA)- molecular testing for mutation
Factor V Leiden thrombophilia
F5 gene
AD (moderately increased risk for venous thromboembolism), AT (significantly increased risk for venous thromboembolism
clinical feature- deep vein thrombosis
Hemophilia A
F8 gene
X-linked
clinical features- hemarthosis, excessive bleeding, can't clot, excessive bruising
10% of carriers have symptoms
Molecular tests- intron 22 gene inversion
Hemophilia B
F9 gene
X-linked
clinical features- hemarthosis, excessive bruising, can't clot
HFE-associated hereditary hemochromatosis
HFE gene
AR
low penetrance- many individuals never develop symptoms
clinical features- high iron, storage in liver, skin, pancreas, heart, joints, testes
treat with phlebotomy
molecular- C282Y (most common mut)
22q11.2 deletion syndrome
AD, 93% de novo
clinical features- congenital heart disease (TOF, IAA, conotruncal defects), immune system dysfunction, palate abnormalities, feeding problems, developmental delay, learning difficulties, hypocalcemia
Alagille syndrome
JAG1 gene
AD
50-70% de novo
clinical features- bile duct paucity on liver biopsy + 3 of: cardiac defects (patent arterosis, TOF), cholestasis, skeletal abnormalities (butterfly vertebrae), eye, facial features, developmental delay, growth delay.
Brugada syndrome
SCN5A gene
AD
clinical features- syncope, arrhythmia, sudden death, may present as SIDS or sudden nocturnal death
clinicat tes- ECG
Hereditary Hemorrhagic Telangiectasia
ACVRL1, ENG genes
AD
clinical features- nosebleeds, mucocutaneous telangiectasia (lips, oral cavity, fingers, and nose), visceral AV malformation (pulmonary, cerebral, hepatic, spinal, gastrointestinal), hemorrhage presents as cerebral AVM
HHT is the result of haploinsufficiency
Holt-Oram syndrome
TBX5 gene
AD
clinical features- malformations of the carpal bones, radial and/or thenar bones, CHD (ASD or VSD), AV block
clinical test- hand X-ray
LEOPARD syndrome
PTPN11 gene
clinical features- Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of the genitalia, Retardation of growth, Sensorineural Deafness, Hypertrophic cardiomyopathy
Noonan syndrome
PTPN11 (50%), SOS1, KRAS, and more genes
AD
clinical features- short stature, low set ears, wide nipples, feeding problems, pulmonic stenosis, HCM, cryptorchidism, renal malformation, lymphedema, scoliosis, learning disability
Williams syndrome
contiguous gene deletion, ELN gene in critical region
AD
clinical features- supravalvar aortic stenosis (SVAS), distinctive facial features, overly friendly/cocktail personality, intellectual disability
HBOC- BRCA1/2
BRCA1/2 genes
AD
clinical features- breast and ovarian cancer, prostate cancer, melanoma, pancreatic cancer
AJ mutations- BRCA1: 185delAG, 5835insC, BRCA2: 6174delT
1/40 AJ frequency
Familial adenomatous polyposis (FAP)
APC gene
AD
clinical features- >100 polyps, 100% get colon cancer if untreated
Attenuated FAP (AFAP)
APC gene mutations in 3' and 5' ends
AD
clinical features- 10-100 polyps
Gardner syndrome
FAP +
clinical features- colon polyps, osteomas, soft tissue tumors, CHRPE, supernumerary teeth
HNPCC/Lynch syndrome
MLH1, PMS2, MSH2, MSH6, EPCAM genes
AD
clinical features- colon cancer
Amsterdam criteria- 3 or more fan members with CRC, 2 generations, 1 CRC before 50
Bethesda criteria- uses MSI and IHC, HNPCC related cancers
MSI and IHC normal- check BRAF for somatic mutations
Turcot syndrome
HNPCC + glioblastoma
Li-Farumeni syndrome
p53 gene
AD
clinical features- sarcoma, bone, brain, breast cancer, adrenocortical carcinoma, choroid plexus carcinoma, leukemia
breast cancer under 35, childhood tumors
Muir-Torre syndrome
Lynch syndrome + tumors of the sweat glands (sebaceous carcinoma)
multiple endocrine neoplasia type 1
MEN1 gene
AD
clinical features- 3 P's (tumors, not necessarily cancer)
Parathyroid
Pituitary
Pancreatic
multiple endocrine neoplasia type 2
RET gene (proto-oncgogene)
AD
clinical features- MEN2A- medullary thyroid cancer, pheochromocytoma
MEN2B- mucosal neuromas (lips and tongue), Marfanoid habitus, medullary thyroid cancer
Neurofibromatosis type II
NF2
AD
clinical features- schwannomas, meningiomas, ependymonas, astrocytoma, bilateral acoustic schwannoma, few cafe au lait
PTEN/ Cowden syndrome
PTEN gene
AD
clinical features- breast cancer, oral papules (trichellomomas), keratosis, GI polyps, macrocephaly, lipomas, usually follicular, rarely papillary, never medullary thyroid cancer.
Tuberous sclerosis
TSC1 and TSC2
AD
clinical features- Skin: hypomelanotic macules, facial angiofibromas, shagreen patch, CNS: subependymal glial nodules, cortical tubers, giant cell astrocytomas, seizures, Renal: angiomyolipomas, epithelial cysts, Heart: cardiac rhabdomyoma, Lung: lymphangiomatosis (LAM), Eye: hamartomas
TSC2 + PKD1 contiguous gene deletion
Von Hippel-Lindau syndrome
VHL gene
AD
clinical features: hemangioblastoma (cerebellum, retina, spinal cord), pheochromocytoma, clear cell renal cell carcinoma
Xeriderma Pigmentosum
XP_ genes
AR
clinical features: severe sun sensitivity
Aarskog syndrome
FGD1 gene
X-linked
clinical features- shawl scrotum, hypertelorism, brachydactyly, short stature, cryptorchidism, cervical vertebral abnormalities, MR
Antley-Bixler syndrome
POR gene
AR
clinical features- ambiguous genitalia, enlarged cystic ovaries, poor masculinization in males, maternal virilization during pregnancy with an affected fetus, craniosynostosis, choanal stenosis or atresia, hydrocephalus, bowing of long bones
Disorder of steroid and cholesterol synthesis
Bardet-Biedl syndrome
BBS1, BBS10 genes
AR
clinical features- night blindness by 7-8 years, truncal obesity, cognitive impairment, renal disease and malformation
Branchiootorenal syndrome (BOR)
EYA1, SIX1 genes
AD
clinical features- inner and outer ear abnormalities (sensorineural hearing loss), brachial fistula, renal malformations
CHARGE syndrome
CHD7 gene
AD
clinical features- Coloboma, Heart anomaly, Choanal atresia, growth and mental Retardation, Genitourinary malformations, Ear anomalies
Coffin-Lowry syndrome
RPS6KA3 gene
X-linked
clinical features- MR, short, fleshy hands, tapering fingers, short stature, microcephaly, kyphoscoliosis
Cornelia de Lange syndrome
NIPBL, SMC1L1
AD, X-linked
clinical features- growth retardation, low hairline, synophrys, diaphragmatic hernia, upper limb abnormalities, ptosis, nystagmus, pulmonary valve stenosis or VSD
Cri du chat
5p-
AD (12% due to unequal segregation of a translocation or from pericentric inversion in 1 parent)
clinical features- cat-like cry, slow growth, microcephaly, MR, hypotonia, strabismus
Fryns syndrome
AR (no known gene)
clinical features- coarse face, cleft lip/palate, diaphragmatic defect, distal digital hypoplasia, MR, agencies of corpus callosum, optic and olfactory tract hypoplasia, GU abnormalities
Majority are stillborn
Greig Cephalopolysyndactyly (GCPS)
GLI3 gene
AD
clinical features- major findings: macrocephaly, ocular hypertelorism, pre axial polydactyly, cutaneous syndactyly, developmental delay, MR, seizures
Pallister-Hall syndrome caused by GLI3 mutations
Joubert syndrome
NPHP1, CEP290, TMEM67
AR
clinical features- Molar tooth sign on U/S during pregnancy (in brain), hypotonia in infancy, MR, pigmentary retinopathy, renal disease
1p36 deletion
most common terminal deletion syndrome
clinical features- hypotonia, developmental delay, growth retardation, obesity, microcephaly, orofacial crediting, cardiomyopathy, seizures, SNHL
Prader-Willi syndrome
15q11-13 maternally imprinted (prader lacks father (deletion on father's gene))- deletion (70%), mat UPD 15% of time, PWS imprinting center defect (1-2%)
clinical features- neonatal hypotonia, developmental delay, hyperphagia leading to obesity, short stature, small hands and feet
Rubenstein-Taybi syndrome
CREBBP, EP300 gene
AD (de novo)
clinical features- microcephaly, beak nose, broad thumbs and toes, cryptorchidism, growth delay, severe MR, congenital heart defect, strabismus, ptosis, sleep apnea, tumors, behavior problems
Smith-Magenis syndrome
RAI1
AD (sporadic unless secondary to parental balanced translocation)
clinical features- early speech delay, sleep problems, stereotypic maladaptive behaviors (self injurious behaviors), self-hugging
Triploidy
69, XXX/XXY/XYY (rare)
sporadic without increased risk of recurrence
majority end in first trimester loss
Parent of origin: maternal- small placental, IUGR with large head, paternal- large placenta, mod symmetric IUGR, microcephalic head
Low hCG during pregnancy)
Gynogenic triploidy- digyny (polar body retention)
Androgenic triploidy- diandry (dispermy)
Trisomy 13, Patau syndrome
20% due to translocation, majority- nondisjuntion
clinical features- holoprosencephaly, polydactyly, seizures, hearing loss, microcephaly, midline defects (cleft lip/palate), omphalocele, cardiac and renal anomalies, MR
Trisomy 18, Edwards syndrome
less than 1% due to translocation
clinical features- DOLL-LIKE clenched hands, 2/5 finger overlap, IUGR, rocker bottom feet, micrognathia, VSD/ASD/PDA, renal anomalies, MR
maternal serum screen- low AFP, hCG, UE3 (estriol)
majority due to maternal nondisjunction
Trisomy 21, Down syndrome
95% de novo, 5% due to robertsonian translocation
clinical features- MR, hypotonia, growth delay, adult cataracts, heart defect, hearing loss, duodenal atresia, early onset Alzheimers, ALL
maternal serum screen- high hCG and inhibit, low PAPP-A, estriol
VACTERL (VATER) association
Vertebral anomalies
Anal atresia
Cardiac malformations (VSD, PDA, TOF, TOV)
Tracheoesophageal fistula
Esophageal atresia
Renal anomalies
Limb anomalies
diagnosis- need 3/7
Wolf-Hirschorn syndrome
4p-
WHSC1/2 genes
87% de novo, 13% due to unbalanced translocation from a balanced parent
clinical features- greek warrior helmet appearance, microcephaly, growth deficiency, MR, seizures, facial asymmetry, ptosis, IgA deficiency, cleft lip/palate, CHD (ASD)
Hidrotic Ectodermal Dysplasia
GJB6 (connexin 30)
AD
clinical features- malformed, thickened, small nails, hypotrichosis (partial or total alopecia), palmoplantar hyperkeratosis, normal sweating and teeth
common mutations- G11R, A88V, V37E
Hypohidrotic Ectodermal Dysplasia (HED)
EDA, EDAR
X-linked (majority)
clinical features-peeling skin at birth, sparse scalp and body hair, inability to sweat, few teeth and conical shape
carriers show mosaicism
Incontinentia Pigmenti
IKBKG (NEMO)
X-linked dominant (most male fetuses miscarry)
clinical features- 4 stages of skin changing, small or malformed teeth, alopecia or woolly hair, nail ridging or pitting, retinal issues
Oculocutaneous Albanism
TYR and OCA2
AR
clinical features- ocular problems, white hair and skin issues
Amyotrophic Lateral Sclerosis (AML/Lou Gehrig Disease)
SOD1 gene
AD
clinical features- increased muscle tone, weakness, muscle wasting, muscle cramps, frontotemperal dementia
Toxic gain of function
Charcot Marie Tooth disease
AD (majority)
PMP22 duplication (most common)
Multiple types- CMT1, 2, Intermediate form, 4, X
clinical features- slowly progressive weakness and atrophy of distal muscles in feet and hands- beginning in 1st-3rd decade, hearing loss, hip dysplasia, foot defority
Duchenne and Becker Muscular Dystrophy (DMD/BMD)
DMD gene (dystrophin protein)
X-linked
clinical features- DMD: symptoms present before age 5, progressive muscle weakness, calf hypertrophy, DCM
BMD: later onset, less sever weakness of quads, activity induced cramping, preservation of neck muscles
Causes: DMD frameshift mutation
BMD: in-frame deletion
Friedreich's Ataxia
FXN gene
AR
clinical features- progressive degeneration of the dorsal root ganglia, spinal cord and cerebellum, progressive limb and gait ataxia before 25 years old, HCM
GAA triplet repeat expansion (66-1700 repeats- disease causing)
Disease mechanism- expansion forms a stable DNA structure that interferes with transcription
Hereditary Neuropathy with Liability to Pressure Palsies (HNPP)
PMP22 gene
AD
clinical features- adult with recurrent focal pressure palsies, mild polyneuropathy, absent ankle reflexes
Limb-Girdle Muscular Dystrophy
CAPN3, FKRP, LMNA, SGCA, DYSF gene
most AR, rare AD subtypes
clinical features- proximal limb weakness, difficulty running and walking, calf hypertrophy, childhood onset (majority)
Myotonic Dystrophy Type 1
DMPK gene (CTG triplet disorder)- gain of function RNA
AD
Mild- 50-150 repeats, cataract and mild myotonia
Classic- 100-1000 repeats, muscle weakness and wasting, myotonia, cataract, and arrhythmia, grip myotonia
Congenital- >2000 repeats, hypotonia, and severe generalized weakness at birth, respiratory insufficiency, early death, MR
Nemaline Myopathy
ACTA1, NEB, TNNT1, TPM2/3 gene
AR or AD
diagnostic features- weakness (face and neck and proximal limb muscles), hypotonia
Spinal Muscular Atrophy
SMN1 and SMN2 genes
AR
clinical features- arthryogryposis, peripheral nerve hypomyelination
SMA Type 1- onset 0-6 months, muscle weakness, early death
SMA Type 2- muscle weakness, onset after 6 months, hypotonia
SMA Type 3- weakness leads to frequent falls, difficulty climbing stairs, onset 2-3 years, SMA Type IV- adult-onset
Majority due to deletions of exon 7 of SMN1 gene, type determined by copy number of SMN2
Congenital Muscular Dystrophy
Types: Fukuyama, Muscle-Eye-Brain, Walker-Warburg, Congenital Muscular Dystrophy
AR
clinical features-muscle weakness at birth, hypotonia, joint contractures
Tay-Sachs disease
HEXA
AR
Lysosomal storage disease
clinical features- infantile (weakness starts at 6 months, exaggerated startle, seizures, vision loss, neurodegeneration, cherry red spot in eye, death in toddler years, juvenile, chronic and adult onset forms
Accumulation of GM2 gangliosides in the brain
Beckwith-Wiedemann syndrome
CDKN1C, H19, KCNQ1OT1 genes
11p15.5
AD (15%)
clinical features-hemihyperplasia, macrosomia, macroglossia, visceromegaly, embryonal tumors (Wilms tumor, neuroblastoma), omphalocele, renal abnormalities
Loss of methylation at DMR2
paternal UPD
mutations in CDKN1C
Sotos syndrome
NSD1 gene
AD
clinical features- macrocephaly, pointed chin, tall stature, delayed motor skills, delayed cognitive, verbal and social development, possible increased risk of tumors- teratoma, neuroblastoma
clinical test- bone age
Ataxia-Telangiectasia
ATM gene
AR (carriers may be at increased risk for cancer)
clinical features- progressive cerebellar ataxia, oculomotor apraxia, conjunctival telangiectasia, immunodef., ionizing radiation sensitivity, cancer risks- lymphoma, leukemia
Amish founder mutation
Bloom syndrome
BLM gene
AR (1/100 carrier frequency in AJ)
clinical features- IUGR, hyper and hypo pigmentation, butterfly distribution sun sensitive telangiectasia, microcephaly, high voice, immunodeficiency, POF/azoospermia
DNA replication and repair error
Fanconi anemia
FAN_ genes, BRCA2 gene
AR
clinical features- short stature, abnormal pigmentation, radial bone abnormality, GU, ear, heart, GI, CNS malformation, hearing loss, developmental delay, progressive bone marrow failure, aplastic anemia
Chromosome breakage test
X-linked Adrenoleukodystrophy
ABCD1 gene
X-linked
clinical features- childhood cerebral: ADHD, total disability within 2 years
adrenomyeloneuopathy insufficiency- late 20's progressive paralysis
adrenocortical insufficiency- majority by age 7.5
increased VLCFA
Peroxisomal disorder
Early Onset Alzheimer Disease
PSEN1 (most common), PSEN2, APP genes
AD
clinical features- dementia, confusion, poor judgement, language disturbance, onset before 50
Angelman syndrome
UBE3A gene
AD- loss of maternally imprinted region (angelman misses mom)- paternal UPD
15q11q13
clinical features- severe developmental delay or MR, severe speech impairment, gait ataxia, inappropriate happy demeanor (frequent laughter), microcephaly, seizures
maternal deletion (65-75%), UBE3A mut (11%), imprinting defect (2.5%), pat UPD (<1%)
CADASIL
NOTCH3 gene
AD
clinical features-Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy
stroke-like episodes before 60, cognitive disturbances, behavioral abnormalities
Canavan disease
ASPA gene
AR
clinical features- macrocephaly, lack of head control, developmental delays, severe hypotonia, never sit or walk or speak
High urine N-acetyl aspartic acid (NAA)
common in AJ population
Familial Dysautonomia
IKBKAP gene
AR
clinical features- progressive, GI dysfunction, vomiting crises, recurrent pneumonia, altered sensitivity to pain and temp., autonomic crises, hypotonia, decreased life expectancy
common in AJ population
Fragile X syndrome
FMR1 gene
X-linked
clinical features- delayed motor and verbal development, MR, prominent jaw and forehead, autistic behavior
carrier females- 20% have POF, FXTAS
carrier males- FXTAS
normal: 5-44
grey zone: 45-54
premutation: 55-199
affected: >200
Huntington Disease
HTT gene (triplet repeat)
AD
clinical features- progressive motor disability, involving both involuntary and voluntary movement, cognitive decline, psychiatric disturbances
Krabbe disease
GALC gene
AR
clinical features- infantile form: irritability to sensory stimuli, muscled hypertonicity, progressive neurologic deterioration, peripheral neuropathy, white matter disease
decreased GALC enzyme activity
Neurofibromatosis 1
NF1 gene
AD
clinical features- 2 or more CAL, 2 or more fibromas, 1 plexiform neurofibroma, axillary or inguinal freckling, optic glioma, Lisch nodules, sphenoid dysplasia
Parkinson Disease
PARK2 (main gene)
AD, AR, multifactorial
clinical features- bradykinesia, rigidity, tremor, asymmetric limb involvement
Juvenile onset- AR- features onset 20-40 years
Rett syndrome
MECP2 gene
X-linked dominant
clinical features- MR, developmental regression (especially lang and hand use), hand wringing, acquired microcephaly, hyperventilation
Wilson disease
ATP7B gene
AR
clinical features- liver disease, jaundice, self-limited hepatitis-like illness, neurologic presentation- movement disorder, disorganization of personality
increased copper storage, high urine copper
X-linked agammaglobinemia (immune deficiency)
BTK gene
X-linked
clinical features- pneumonia, sinusitis, sepsis, meningitis, (infections)
low IgG, <1% B-cells
Familial Mediterranean Fever
MEFV
AR
clinical features- Type 1: recurrent febrile episodes with inflammation of peritoneal, synovial lining, pleuritis
Type 2: amyloidosis
Alpha-1-antitrypsin deficiency
SERPINA1
AR
clinical features- adult COPD, childhood and adult liver disease, increased risk for cirrhosis, age of onset: 40-50 if a smoker
CFTR-related disorders (Cystic fibrosis)
CFTR gene
AR
clinical features- chronic airway infection, chronic sinusitis, maconeum ileum, malabsorption due to pancreatic insufficiency, CBAVD in males
tests: sweat test, sequencing, common muts
Blepharophimosis, Ptosis, Epicanthus Inversus (BPES)
FOXL2 gene
AD (50% de novo)
clinical features- Blepharophimosis (eye findings), ptosis, epicanthys inverses, telecanthus
Nonsyndromic hearing loss
GJB2, GJB6 (connexon 26 and 30)
AR
clinical features- SNHL
Hermansky-Pudlak syndrome
HPS1, AP3B1, and more
AR
clinical features- oculocutaneous albinism and bleeding diathesis, hypopigmentation of the skin and hair, nystagmus, reduced iris pigment, foveal hyperplasia, can develop skin cancer
Jervell and Lange-Nielsen syndrome
KCNQ1 and KCNE1
AR
clinical features- long QT and hearing loss
Leber Hereditary Optic Neuropathy
MTND1, MTND4, MTND5, MTND6
Mitochondrial inheritance
clinical features- blurred/clouded vision progressing to degeneration of the retinal nerve, optic atrophy- lots of eye findings
Pendred syndrome
SLC26A4
AR
clinical features- bilateral SNHL, temporal bone abnormalities (aqueductal stenosis), vestibular abnormalities, goiter, abnormal thyroid function
Usher syndrome
11 USH genes
AR
clinical features- congenital profound hearing loss, balance problems, retinitis pigments (RP)
Waardenburg syndrome
PAX3
AD
clinical features- SNHL, heterchromic irides, white forelock, early graying, leukodermia, dystrophia canthorum, neural tube defect
4 types of Waardenburg
Type 4 + Hirschprung disease
Achondroplasia
FGFR3 (G1138A)
AD (80% de novo)
clinical features- short stature, rhizomelic shortening, trident hand, frontal bossing, mid face hypoplasia, macrocephaly, spinal cord depression
Cleidocranial dysplasia
RUNX2
AD
clinical features- delayed closure of the cranial sutures, hypo plastic or aplastic clavicles, multiple dental abnormalities, large anterior fontanel, mid face hypoplasia, brachydactyly, hearing loss, normal intellect
Diastrophic Dysplasia
SLC26A2
AR
clinical features- limb shortening, normal-sized skull, hitchhiker thumbs, small chest, large joint contracture, cleft palate, cystic ear swelling, ulnar deviation of fingers, clubfoot, low tone
Craniosynostosis (FGFR-related)
FGFR1, FGRF2, FGFR3
AD
clinical features- bicoronal craniosynostosis or cloverleaf skull, hand abnormalities (Apert syndrome- mitten hands and feet), developmental delays/MR, hearing loss, visual impairment
FGFR1- Pfeiffer
FGFR2- Crouzon, Jackson-Weiss, Apert, Pfeiffer 2 and 3
FGFR3- Crouzon
Hypochondrplasia
FGFR3 gene
AD
clinical features- short stature, stocky build, rhino or mesomelia, brachydactyly, mild joint laxity, macrocephaly, scoliosis, mild-mod MR (more mild Achondroplasia)
Multiple Exostoses syndrome
EXT1, EXT2 genes
AD
clinical features- boney growths (exostoses/osteochondromas), limb length inequity and bowed long bones
Osteogenesis Imperfecta
COL1A1, COL1A2 genes
AD (rarely AR)
clinical features- multiple bone fractures or breaks, short stature, blue sclera, dentinogenesis imperfect
Type 2- perinatal lethal, hips in frog-leg position (little budda)
Type 3- sever, skull descends on cervical spine, obstructive hydrocephalus
Saethre-Chotzen syndrome
TWIST1 gene
AD
clinical features- coronal synostosis, facial asymmetry, ptosis, 2/3 hand syndactyly, short stature, radioulnar synostosis, cleft palate, maxillary hypoplasia, congenital heart defects
Congenital Contractural Arachnodactyly (Beels syndrome)
FBN2 gene
AD
clinical features- marfanoid appearance, long fingers, "heel ear" (crumpled ear), joint contracture, heart defect
Ehlers-Danlos syndrome (EDS) Types 1 and 2- Classic Type
COL5A1, COL5A2
AD
clinical features- skin hyper extensibility, widened atrophic scars, joint hypermobility, smooth velvety skin, easy bruising, hypotonia, chronic pain, aortic root dilatation
EDS Type 3- Hypermobility type
TNXB gene (research basis)
AD
clinical features- joint hypermobility, smooth velvety skin, chronic pain, easy bruising, recurrent dislocation, aortic root dilatation and MVP
EDS Type IV- Vascular type
COL3A1 gene
AD
clinical features- arterial rupture, intestinal rupture, uterine rupture during pregnancy
minor criteria- thin, translucent skin, easy bruising, thin lips, small chin, thin nose, large eyes, aged appearance on hands, pneumothorax, joint mobility, tendon/muscle rupture, varicose veins, CHD, clubfoot
EDS type VI- Kyphoscoliotic type
PLOD1 gene
AR*
clinical features- hyper extensible skin, thin scars, easy bruising, generalized joint laxity, severe muscle hypotonia, progressive, scoliosis
Minor features- widened scars, marfanoid habits, rupture of medium-sizes arteries
Marfan syndrome
FBN1 gene
AD
clinical features- 2 body systems and minor involvement of a 3rd
Major: dilatation or dissection of the ascending aorta, pectus carnitum or excavatum, reduced upper:lower segment or arm span: height, scoliosis, pea plans, high palate, reduced elbow extension, octopi, lentis, lumbosacral dural ectasia, FBN1 mutation
Ataxia with Oculomoter Apraxia Type 1 and 2
APTX and SETX gene
AR
clinical features- childhood onset of slowly progressive cerebral ataxia, followed by oculomoter apraxia and a severe primary motor peripheral axonal motor neuropathy- progresses to external ophlamoplegia
Cockayne syndrome
ERCC6, ERCC8 genes
AR
clinical features- Type 1: normal prenatal growth, severe FTT, progressive deterioration of vision, hearing, CNS, peripheral nervous system
Type 2: growth failure at birth, little or no neurological development, kyphosis, scoliosis, joint contracture
Type 3: normal growth and development or late onset, XP, early skin cancer, MR, spasticity, short stature, hypogonadism
Hutchinson-Gilford Progeria syndrome
LMNA
AD (all de novo, APA)
clinical features- short stature, head large for face, diminished fat, generated alopecia, delayed and crowded teeth, delayed fontanelle closure, small chin, thin limbs, tight joints, sclerodermatou skin changes over lower abdomen and thighs
Aging disease
X-linked Adrenal Hypoplasia Congenita
NROB1
X-linked
clinical features- acute onset adrenal insufficiency, crytptochidism, delayed puberty
carrier females- may have adrenal insufficiency or hypogonadotrophic hypogonadism
1/3 contiguous gene deletion with DMD gene
2/3 isolated CAH (half de novo)
21-Hydroxylase-deficienct CAH
CYP21A2 gene
AR
clinical features- salt wasting, virilized female, precocious puberty or adrenarche, childhood variation in males
Non-classic form: variable postnatal virilization, no salt wasting
Androgen Insensitivity Syndrome (AIS)
AR gene
X-linked
clinical features- evidence of feminization (undermasculinization) of the external genitalia, abnormal secondary sexual development, infertility for 46, XY karyotype
Spectrum- complete AIS- with typical female genitalia
Partial AIS- female, male, or ambiguous genitalia
Mild AIS- with normal male genitalia
Kallman syndrome
KAL1 and FGFR1
X-linked, AD
clinical features- hypogonadotrophic hypogonadism and anosmia- present with delayed puberty development
Type 1: can also include miss or hand movements, ataxia, GU anomaly, high palate, pea caves
Type 2: MR, cleft lip/palate, cryptorchidism, choanal atresia, CHD, SNHL
Low FSH and LH, low testosterone in males
Klinefelter syndrome
XXY (55% due to maternal nondisjunction)
clinical features- tall stature, slightly delayed motor and language skills, increased risk for learning difficulty, small testes, azoospermia and infertility, gynecomastia, increased risk for germ cell tumors (1%)
McCune-Albright syndrome
GNA5 gene
sporadic inheritance
clinical features- irregular cafe au lait spot ("coast of Maine"), polyostotic fibrous dysplasia, pathological fracture, can have deafness and blindness, precocious puberty, hyperthyroidism, ovarian cyst
Transient Neonatal Diabetes Mellitus
HYMAI, PLAGL1 genes
UPD isodisomy chromosome 6, paternal dup on chrom 6, methylation defect
clinical features- diabetes in the first 6 weeks of life, severe IUGR, dehydration, hyperglycemia, occasional macroglossia and umbilical hernia
Turner syndrome
45,X (SHOX gene)
majority paternal in origin
clinical features- short stature, congenital lymphedema, growth failure, normal intelligence (10% have sig. delays), coartation of the aorta, bicuspid aortic valve, HLHS (hypo plastic left heart syndrome), gonadal dysgenesis, hypothyroidism, diabetes, strabismus, SNHL, Crohns, renal malformation, osteoporosis, wide-spaced nipples, webbed neck
Alport syndrome
COL4A5- X-linked (majority)
COL4A3 and COL4A4- AR
clinical features- progressive renal disease with cochlear and ocular abnormalities to isolated hematuria with a benign coarse
Polycystic Kidney Disease
PKD1, PKD2- AD
PKHD1- AR
clinical features- AD form: enlargement of both kidneys, renal cysts, hematuria, polyuria, kidney stones, UTI, liver cysts, pancreas and intestine, heart valve defects, intracranial aneurysm
AR form: fetal or neonatal death, impaired lung formation, pulmonary hypoplasia due to oligohydramnios, renal failure, hepatic fibrosis, most present prenatally or early infancy
Galactosemia
GALT gene
AR
carrier frequency: 1/60
Duarte: N314D common mutation, makes 25% enzyme activity
Classic: Q188R common mutations in caucasians, 0% enzyme activity, K285N common mutation in Eastern European, 0% enzyme activity
Treat with low galactose diet
clinical features- lethargy, jaundice, FTT, liver damage, sepsis, cataracts
THIS SET IS OFTEN IN FOLDERS WITH...