GENETIC/CHROMOSOMAL SYNDROMES
Fetal alcohol Pierre Robin Stickler Treacher Collins
DiGeorge Marfan syndrome
spectrum disorder sequence syndrome syndrome
heterozygous chromosomal
hypoplasia of the mandible
deletion at 22q11.2® Defective prenatally exposed to alcohol autosomal dominant CT autosomal-dominant disorder
that occurs before 9th week Inherited CT disorder
development of the pharyngeal (time, amount) disorder of fibrillin gene of craniofacial development
of development
pouch system
• Marfanoid habitus (tall, • Malar hypoplasia
CATCH-22 • Macrocephaly • Flat face
long limbs + high arched • Cleft palate • Down slanting palpebral
• Cardiac (TOF – cyanotic + FTT) • Intrauterine growth • Upturned nose
palette) • Micrognathia fissures
• Abnormal facies restriction (IUGR) • Prominent eyes
• Hypermobility • Glossoptosis • Lower lip defect
(micrognathia, inward eyes) • Smooth philtrum • Hypotonia
• Arachnodactyly (test) (tongue back in mouth) • Ear + eye abnormality
• Thymus absent (?MG) • Joint abnormality • Hypermobility
• Tricuspid valve prolapse • Cleft palate
• Cleft palette
• Murmur = MVP, AR
• HypoPTH = hypoCa • inattentive
• Aortic dissection
• Chr 22 • Lung hypoplasia • Underdevelopment of the
Other: • Pneumothorax • Feeding/ breathing
• Altered surfactant facial bones + airway can
• Chest wall deformities difficulties
• Recurrent chest infections production lead to airway obstruction
(kyphoscoliosis, pectus • Scoliosis
• Larynx-trachea-oesophageal • Poor academics, impulse • Colobomas (defect in iris)
excavatum)
anomalies control
• Upward lens dislocation
Rx:
Ø BB and ARB for HTN
Ø PT = strengthen joints
Ø Genetic counsel
Ø Yearly ECHO and
ophthal reiew
Cause Physical dysmorphia Assoc Mx
• Low set ears, • ENT –conductive hearing loss (recurrent otitis Ante-natal screening
• epicanthic folds, media, glue ear) • NIPT
• upslanting palpebral fissures, • Vision loss (myopia, cataracts, strabismus) • NT scan
• single palmar crease • CVS: AVSD (ASD, VSD), PDA, TOF, aberrant SCA • Biochemical (B-HCG, PAPP-A)
Down’s Trisomy 21
• clinodactyly (bending of 5th finger) • Resp: small nose ® OSA, Recurrent chest infections • CVS or amniocentesis
• inguinal hernia (crypto-orchidism) • GIT: Duodenal atresia, Hirschsprungs disease
• Endo: hypothyroidism (10-20%)
• Cancers = leukeamia
• small eyes, cleft palette and lip • structural brain defect ® learning delay
Patau Trisomy 13
• polydactyly • cardiac and renal malformations
• Prominent occiput and micrognathia
• LBW
Edward Trisomy 18 • Rocker bottom feet
• cardiac and renal malformations
• Flexed overlapping fingers
• Short stature • Recurrent AOM and UTI • GH therapy (for short stature)
• webbed neck + widely spaced nipples • Aortic Coarctation • E2 + PG (for 2nd sex characteristics
Turner 45XO • wide carrying angle (cubitus valgus) • Hypothyroidism and regulate [periods)
• koilonychia • HTN, DM, OP, obesity • Fertility support
• Ovary dysgenesis = amenorrhoea, early miscarriage
• Tall thin men • Seminiferous tubules dysgenesis ® Infertile • TT injections
o XS central adiposity • Reduced libido • Breast reduction surgery
Klinefelter 46XXY
• Wide hips + less facial/body hair • Learning difficulties (e.g. dyslexia and shy • MDT – speech path, OT, PT,
• small testes + gynecomastia • COMP (rare) è BC, OP, DM, anxiety and depression educational support
• Short stature • POOR FEEDING – FTT , puberty delay MDT and supportive Rx:
• Broad forehead • CHD (ASD, pulm. Stenosis, HOCM) • ECHO referral for CHD
• webbed neck + widely spaced nipples • Renal malformation • Audiology assessment
Noonan AD mutation • hypertelorism (wide space between eyes) • Hearing loss • FBC + APTT
• Downsloping eyes + ptosis • Behavioural problems • Yearly check up
• Lymphodema • Crypto-orchidism – infertility • Plot growth curves – need GH
• COMP (rare) è Leukaemia and neuroblastoma supplementation
• Cleft palette • Cardiac malformation (Carotid artery anomaly) • FISH to diagnose
Velocardiofacial • High-arched palette • ADHD • CMP – (check for hypoCa)
AD mutation
syndrome • Broad nose ridge • Assoc. PTH and thymus hypoplasia (DiGeorge • FBC + complement
Syndrome)
• Broad forehead, short nose, • VERY SOCIABLE PERSONALITY No cure ® MDT approach
• Starburst eyes (star-like pattern on iris) • Hypercalcemia ® Nephrocalcinosis • BP monitor
Williams
Chr 7 deletion • WIDE MOUTH + big smile • Supravalvular AS • ECHO
syndrome
• ADHD • Low Ca diet
• HTN
Cri du chat Chr 5 deletion • Developmental, delay • MDt
• Learning and speech delay
(part only)
• Big head + big testes (macro-orchid) • Genetic test – measure # of CGG
• CVS – MVP
• Long face + large everted ears (mickey repeats > 50)
Fragile X Tri-repeat • MSK – scoliosis, joint laxity (hypotonia)
mouse) • MDT approach ® e.g. Speech path
syndrome FMR1 • Intellectual disability– ADHD, hyperactive (IQ 20-80)
• Large testes after puberty • OCD = SSRI
• Seizures
• ADHD - Stimulants
Charcot- Chr 17 • Pes cavus (high foot arch) •
• Sensory and motor neuropathy
Marie-Tooth duplicate
• Blond hair, blue eyes and fair skin No cure- MDT approach
Angelman • “happy puppet demeanour
Chr 15 – both • Microencephaly, sunken nasal ridge • Parental education
syndrome • Wide-based ataxic gait + flexed elbows and wrist
copies from • Widely spaced teeth • PT, OT, psychology, social worker
(UBE3A gene) • Severe intellectual disability (non-verbal) – ADHD,
father • Prominent lower lip and small chin • Anti-epileptics if needed
MALE epilepsy
• Fascination with water
• Narrow forehead + almond shaped eyes No cure – supportive care (control wt)
• Initially feeding difficulties ®FTT + Neonatal
Prader-Willi Chr 15 – both • Triangular mouth • Give GH – for muscle development
hypotonia
syndrome copies from • Short stature and small hands/feet • Dietician (control diet)
• After – constant hyperphagia ® XS wt gain
[FEMALE] mother • Underdeveloped genitals= infertility • Social workers
• MH issues + moderative learning disability
• PT, OT, psychologists
Beckwith- Macroglossia • Omphalocele •
Overgrowth Hypoglycemia
Wiedemann • Hyperinsulinemia (B-cell hyperplasia)
disorder
syndrome • Wilms’ tumour & Kidney anomalies
Alagille JAG1 mutant • Prominent forehead, bulbous nose tip • Biliary atresia – Jaundice (conj. Bilirubin)
syndrome gene • Pointed chin, deep set eyes • Also: PS, ToFallot
Variant globin • Chipmunk face – XS bone turnover and
Thalassemia • Massive splenomegaly
gene proliferation of bone marrow
*****Other chr. Issue = Translocation e.g. AML T9:22 (ph chromosome) + | Mosaicism = Chromosomal abnormality occurs after conception *****
Down’s Patau Edward Turner Klinefelter Fragile X William’s Alagille
Fetal alcohol Pierre Robin Stickler Treacher Collins
DiGeorge Marfan syndrome
spectrum disorder sequence syndrome syndrome
heterozygous chromosomal
hypoplasia of the mandible
deletion at 22q11.2® Defective prenatally exposed to alcohol autosomal dominant CT autosomal-dominant disorder
that occurs before 9th week Inherited CT disorder
development of the pharyngeal (time, amount) disorder of fibrillin gene of craniofacial development
of development
pouch system
• Marfanoid habitus (tall, • Malar hypoplasia
CATCH-22 • Macrocephaly • Flat face
long limbs + high arched • Cleft palate • Down slanting palpebral
• Cardiac (TOF – cyanotic + FTT) • Intrauterine growth • Upturned nose
palette) • Micrognathia fissures
• Abnormal facies restriction (IUGR) • Prominent eyes
• Hypermobility • Glossoptosis • Lower lip defect
(micrognathia, inward eyes) • Smooth philtrum • Hypotonia
• Arachnodactyly (test) (tongue back in mouth) • Ear + eye abnormality
• Thymus absent (?MG) • Joint abnormality • Hypermobility
• Tricuspid valve prolapse • Cleft palate
• Cleft palette
• Murmur = MVP, AR
• HypoPTH = hypoCa • inattentive
• Aortic dissection
• Chr 22 • Lung hypoplasia • Underdevelopment of the
Other: • Pneumothorax • Feeding/ breathing
• Altered surfactant facial bones + airway can
• Chest wall deformities difficulties
• Recurrent chest infections production lead to airway obstruction
(kyphoscoliosis, pectus • Scoliosis
• Larynx-trachea-oesophageal • Poor academics, impulse • Colobomas (defect in iris)
excavatum)
anomalies control
• Upward lens dislocation
Rx:
Ø BB and ARB for HTN
Ø PT = strengthen joints
Ø Genetic counsel
Ø Yearly ECHO and
ophthal reiew
Cause Physical dysmorphia Assoc Mx
• Low set ears, • ENT –conductive hearing loss (recurrent otitis Ante-natal screening
• epicanthic folds, media, glue ear) • NIPT
• upslanting palpebral fissures, • Vision loss (myopia, cataracts, strabismus) • NT scan
• single palmar crease • CVS: AVSD (ASD, VSD), PDA, TOF, aberrant SCA • Biochemical (B-HCG, PAPP-A)
Down’s Trisomy 21
• clinodactyly (bending of 5th finger) • Resp: small nose ® OSA, Recurrent chest infections • CVS or amniocentesis
• inguinal hernia (crypto-orchidism) • GIT: Duodenal atresia, Hirschsprungs disease
• Endo: hypothyroidism (10-20%)
• Cancers = leukeamia
• small eyes, cleft palette and lip • structural brain defect ® learning delay
Patau Trisomy 13
• polydactyly • cardiac and renal malformations
• Prominent occiput and micrognathia
• LBW
Edward Trisomy 18 • Rocker bottom feet
• cardiac and renal malformations
• Flexed overlapping fingers
• Short stature • Recurrent AOM and UTI • GH therapy (for short stature)
• webbed neck + widely spaced nipples • Aortic Coarctation • E2 + PG (for 2nd sex characteristics
Turner 45XO • wide carrying angle (cubitus valgus) • Hypothyroidism and regulate [periods)
• koilonychia • HTN, DM, OP, obesity • Fertility support
• Ovary dysgenesis = amenorrhoea, early miscarriage
• Tall thin men • Seminiferous tubules dysgenesis ® Infertile • TT injections
o XS central adiposity • Reduced libido • Breast reduction surgery
Klinefelter 46XXY
• Wide hips + less facial/body hair • Learning difficulties (e.g. dyslexia and shy • MDT – speech path, OT, PT,
• small testes + gynecomastia • COMP (rare) è BC, OP, DM, anxiety and depression educational support
• Short stature • POOR FEEDING – FTT , puberty delay MDT and supportive Rx:
• Broad forehead • CHD (ASD, pulm. Stenosis, HOCM) • ECHO referral for CHD
• webbed neck + widely spaced nipples • Renal malformation • Audiology assessment
Noonan AD mutation • hypertelorism (wide space between eyes) • Hearing loss • FBC + APTT
• Downsloping eyes + ptosis • Behavioural problems • Yearly check up
• Lymphodema • Crypto-orchidism – infertility • Plot growth curves – need GH
• COMP (rare) è Leukaemia and neuroblastoma supplementation
• Cleft palette • Cardiac malformation (Carotid artery anomaly) • FISH to diagnose
Velocardiofacial • High-arched palette • ADHD • CMP – (check for hypoCa)
AD mutation
syndrome • Broad nose ridge • Assoc. PTH and thymus hypoplasia (DiGeorge • FBC + complement
Syndrome)
• Broad forehead, short nose, • VERY SOCIABLE PERSONALITY No cure ® MDT approach
• Starburst eyes (star-like pattern on iris) • Hypercalcemia ® Nephrocalcinosis • BP monitor
Williams
Chr 7 deletion • WIDE MOUTH + big smile • Supravalvular AS • ECHO
syndrome
• ADHD • Low Ca diet
• HTN
Cri du chat Chr 5 deletion • Developmental, delay • MDt
• Learning and speech delay
(part only)
• Big head + big testes (macro-orchid) • Genetic test – measure # of CGG
• CVS – MVP
• Long face + large everted ears (mickey repeats > 50)
Fragile X Tri-repeat • MSK – scoliosis, joint laxity (hypotonia)
mouse) • MDT approach ® e.g. Speech path
syndrome FMR1 • Intellectual disability– ADHD, hyperactive (IQ 20-80)
• Large testes after puberty • OCD = SSRI
• Seizures
• ADHD - Stimulants
Charcot- Chr 17 • Pes cavus (high foot arch) •
• Sensory and motor neuropathy
Marie-Tooth duplicate
• Blond hair, blue eyes and fair skin No cure- MDT approach
Angelman • “happy puppet demeanour
Chr 15 – both • Microencephaly, sunken nasal ridge • Parental education
syndrome • Wide-based ataxic gait + flexed elbows and wrist
copies from • Widely spaced teeth • PT, OT, psychology, social worker
(UBE3A gene) • Severe intellectual disability (non-verbal) – ADHD,
father • Prominent lower lip and small chin • Anti-epileptics if needed
MALE epilepsy
• Fascination with water
• Narrow forehead + almond shaped eyes No cure – supportive care (control wt)
• Initially feeding difficulties ®FTT + Neonatal
Prader-Willi Chr 15 – both • Triangular mouth • Give GH – for muscle development
hypotonia
syndrome copies from • Short stature and small hands/feet • Dietician (control diet)
• After – constant hyperphagia ® XS wt gain
[FEMALE] mother • Underdeveloped genitals= infertility • Social workers
• MH issues + moderative learning disability
• PT, OT, psychologists
Beckwith- Macroglossia • Omphalocele •
Overgrowth Hypoglycemia
Wiedemann • Hyperinsulinemia (B-cell hyperplasia)
disorder
syndrome • Wilms’ tumour & Kidney anomalies
Alagille JAG1 mutant • Prominent forehead, bulbous nose tip • Biliary atresia – Jaundice (conj. Bilirubin)
syndrome gene • Pointed chin, deep set eyes • Also: PS, ToFallot
Variant globin • Chipmunk face – XS bone turnover and
Thalassemia • Massive splenomegaly
gene proliferation of bone marrow
*****Other chr. Issue = Translocation e.g. AML T9:22 (ph chromosome) + | Mosaicism = Chromosomal abnormality occurs after conception *****
Down’s Patau Edward Turner Klinefelter Fragile X William’s Alagille
