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Departement Of Departement Of Paediatrics M.L.B.M.C. Paediatrics M.L.B.M.C. Jhansi.Jhansi.
•APPROACH TO A APPROACH TO A DYSMORPHIC CHILDDYSMORPHIC CHILD
Dr.shashank kumarDr.shashank kumar
– ““if it were not for the great variability if it were not for the great variability among individuals, medicine might as among individuals, medicine might as well be a science and not and art”well be a science and not and art”
Sir william osler, Sir william osler, 18921892
• Though greater heights are being Though greater heights are being achieved in molecular diagnostics achieved in molecular diagnostics of genetic diseases ,the first step of genetic diseases ,the first step in the approach to a Dysmorphic in the approach to a Dysmorphic child still is “clinical”child still is “clinical”
DysmorphologyDysmorphology
Coined by Dr.David Smith in the Coined by Dr.David Smith in the 1966 to describe the study of 1966 to describe the study of human congenital malformation, human congenital malformation, derived from ”dys”(disordered) and derived from ”dys”(disordered) and “morph” (shape,form) .“morph” (shape,form) .
It encompass the variability of It encompass the variability of normal physical trait as well as normal physical trait as well as pathologic features resulting from pathologic features resulting from abnormal development.abnormal development.
Accurate diagnosisAccurate diagnosis
Allow for decision making and Allow for decision making and communicating in the followings:-communicating in the followings:-
Prognosis.Prognosis.Treatment options.Treatment options.
Occult abnormalities.Occult abnormalities.Recurrence risk.Recurrence risk.Pathogenesis.Pathogenesis.Natural Hx.Natural Hx.
Pre-natal vs. Post-natal Pre-natal vs. Post-natal onset of developmental onset of developmental
problemsproblemsPre-natal:Pre-natal:Alteration of pregnancy:Alteration of pregnancy:Gestational timing , onset & nature of fetal Gestational timing , onset & nature of fetal
activity and amount of amniotic fluid.activity and amount of amniotic fluid.
Alteration noted at birth:Alteration noted at birth: Increased incidence of breech presentation.Increased incidence of breech presentation.
Prenatal onset of growth deficiency.Prenatal onset of growth deficiency. Difficulty with neonatal adaptationDifficulty with neonatal adaptation..
SINGLE PRIMARY DEFECT IN SINGLE PRIMARY DEFECT IN DEVELOPMENTDEVELOPMENT
Subcategorized according to the nature Subcategorized according to the nature of error in morphogenesis which can be of error in morphogenesis which can be helpful to prognosis.helpful to prognosis.
44 modes of pathogenesis for birth modes of pathogenesis for birth defects in humans.defects in humans.
1.1. Deformation.Deformation.2.2. Disruption.Disruption.3.3. Dysplasia.Dysplasia.
4.4. MalformationMalformation..
SINGLE PRIMARY DEFECT IN SINGLE PRIMARY DEFECT IN DEVELOPMENT (cont.)DEVELOPMENT (cont.)
Malformation.Malformation.Term used for permanent changes produced by Term used for permanent changes produced by
an intrinsic abnormality of development in a an intrinsic abnormality of development in a body structure during prenatal life.body structure during prenatal life.
The actual mechanism is unknown but may The actual mechanism is unknown but may involved error in embryonic cell proliferation, involved error in embryonic cell proliferation, differentiation , migration, & programmed differentiation , migration, & programmed death as well as cell to cell communication.death as well as cell to cell communication.
e.g.. Pyloric stenosis, cleft palate,e.g.. Pyloric stenosis, cleft palate,
Cardiac septal defect.Cardiac septal defect.
SINGLE PRIMARY DEFECT IN SINGLE PRIMARY DEFECT IN DEVELOPMENT (cont.)DEVELOPMENT (cont.)
Deformation.Deformation.Those anomalies caused by unusual mechanical Those anomalies caused by unusual mechanical
pressure on the developing fetus usually pressure on the developing fetus usually during the last trimester of gestation.during the last trimester of gestation.
Mechanical stress may be either extrinsic or Mechanical stress may be either extrinsic or intrinsic.intrinsic.
Recurrence risk is low.Recurrence risk is low.
SINGLE PRIMARY DEFECT IN SINGLE PRIMARY DEFECT IN DEVELOPMENT (cont.)DEVELOPMENT (cont.)
Dysplasia.Dysplasia.Structural defects resulting from abnormal Structural defects resulting from abnormal
cellular organization or function that affect cellular organization or function that affect one general tissue throughout the body.one general tissue throughout the body.
Tissue dysplasia tend to persist or even Tissue dysplasia tend to persist or even worsen with age.worsen with age.
Prognosis depend on the natural hx. Of the Prognosis depend on the natural hx. Of the diseasedisease
SINGLE PRIMARY DEFECT IN SINGLE PRIMARY DEFECT IN DEVELOPMENT (cont.)DEVELOPMENT (cont.)
Disruption.Disruption.Affect structures that had been undergoing Affect structures that had been undergoing
normal development & growth in utero.normal development & growth in utero.
Usually it is local & adjacent structure are often Usually it is local & adjacent structure are often normal.normal.
Caused by severe mechanical stress: Amniotic Caused by severe mechanical stress: Amniotic band , Viral infections , Tissue ischemia.band , Viral infections , Tissue ischemia.
Patients usually have the potential for normal Patients usually have the potential for normal intellectual development & physical growth. intellectual development & physical growth.
Most are sporadic , rec.risk is v.low.Most are sporadic , rec.risk is v.low.
Malformation Deformation
Disruption
Interrelationships between malformations,deformations,and
disruptions
ETIOLOGY ETIOLOGY PATHOGENESIS PATHOGENESIS PHENOTYPEPHENOTYPE
Autosomal dominanant Mesenchymal blastomaAutosomal dominanant Mesenchymal blastoma
genegene
Hyperthyrodism Accelerated osseous Hyperthyrodism Accelerated osseous CrainosynstosisCrainosynstosis
maturationmaturation
Microcephaly Lack of growth stretchMicrocephaly Lack of growth stretch
across suturesacross sutures
TTypes of Birth Defects:ypes of Birth Defects:
1.1. Major vs. Minor abnormalities.Major vs. Minor abnormalities.
2.2. Isolated vs. Multiple anomalies.Isolated vs. Multiple anomalies.
3.3. Associations & Complexes.Associations & Complexes.
4.4. Sequences & Syndromes.Sequences & Syndromes.
11.Major vs. Minor anomalies:.Major vs. Minor anomalies:
Major malformations.Major malformations. Those that have medical & /or social Those that have medical & /or social
implications. Often require surgical implications. Often require surgical repair.repair.
Minor malformationsMinor malformations..
Have Mostly cosmetic significance.Have Mostly cosmetic significance.
Normal variants.Normal variants.
2.Isolated vs. Multiple Anomalies:2.Isolated vs. Multiple Anomalies:
Most are isolated affecting a single body Most are isolated affecting a single body site.site.
2/3 of the major defect are isolated , 2/3 of the major defect are isolated ,
and of multifactorial inheritance with and of multifactorial inheritance with increased frequency in some families & increased frequency in some families & racial groups. racial groups.
3.Associations and complexes3.Associations and complexes::
Association:Association:Non-random combination of anomalies in Non-random combination of anomalies in
which the individual component occurs which the individual component occurs together more frequently than would be together more frequently than would be expected by chance and aren’t enough to expected by chance and aren’t enough to justify definition as a syndromejustify definition as a syndrome..
e.g.. VACTERAL , CHARGE , MURCS .e.g.. VACTERAL , CHARGE , MURCS .
The recurrence risk is extremely lowThe recurrence risk is extremely low
Prognosis depends on the lesionsPrognosis depends on the lesions
Association contd:Association contd: • VACTERL
ASSOCIATION number of congenital
anomalies occurring together• V Vertebral anomalies• A imperforate Anus• C Cardiac abnormalities• TE Tracheo Esophageal fistula
• R Radial and Renal dysplasia• L Limb deformity
• CHARGE ASSOCIATION
• C Coloboma• H congenital Heart
disease• A Choanal Atresia• R mental Retardation• G Genito Urinary anomalies• E Ear anomalies
3.Associations and complexes 3.Associations and complexes (cont.):(cont.):
Complex:Complex:Anomalies of several different Anomalies of several different
structure all of which lie together in structure all of which lie together in the same local body region during the same local body region during embryonic development.embryonic development.
e.g. Poland anomaly , Sacral e.g. Poland anomaly , Sacral agenesis.agenesis.
POLAND ANOMALYPOLAND ANOMALY• Dextrocardia(in left-sided Poland Dextrocardia(in left-sided Poland
sequence) sequence) • Ectopic Liver tissue Ectopic Liver tissue • unilateral hypoplasia or absence of unilateral hypoplasia or absence of
pectoralis major muscle pectoralis major muscle • absence of pectoralis minor absence of pectoralis minor
muscle muscle • hypoplastic ribs hypoplastic ribs
fused ribs fused ribs• unilateral hypoplasia or absence of unilateral hypoplasia or absence of
nipple nipple unilateral hypoplasia or absence of unilateral hypoplasia or absence of areola areola unilateral absence of breast unilateral absence of breast
• hemivertebrae hemivertebrae • unilateral syndactyly unilateral syndactyly
unilateral unilateral brachydactylybrachydactyly unilateral unilateral oligodactylyoligodactyly
• hypoplasia of latissimus dorsi hypoplasia of latissimus dorsi muscle,serratus anterior muscle,serratus anterior muscle,infraspinatus muscle,infraspinatus muscle,supraspinatus,deltoid muscle,supraspinatus,deltoid musclemuscle
4.Sequences and 4.Sequences and syndromes:syndromes:
Sequence:Sequence:A single underlying abnormality give rise is A single underlying abnormality give rise is
a cascade of structural changes that a cascade of structural changes that might seem to be unrelated to each other might seem to be unrelated to each other ( Field- defect). ( Field- defect).
Original defect is malformation. e.g..NTD Original defect is malformation. e.g..NTD sequence, Potter oligohydramion sequence, Potter oligohydramion sequence.sequence.
Disruption sequence (Amniotic band).Disruption sequence (Amniotic band).
Deformation sequence.Deformation sequence.
Potter Potter oligohydramniosoligohydramnios sequence sequence• Typical physical appearance of neonate due to Typical physical appearance of neonate due to
oligohydramnios which occurs due to BILATERAL RENAL oligohydramnios which occurs due to BILATERAL RENAL AGENESIS, atresia of ureter or urethra,amnioitc rupture, AGENESIS, atresia of ureter or urethra,amnioitc rupture, uteroplacental insufficiencyuteroplacental insufficiency
• Potter facies:Potter facies: Affected infants have a flattened nose, Affected infants have a flattened nose, recessed chin, prominent epicanthal folds, and low-set recessed chin, prominent epicanthal folds, and low-set abnormal ears.abnormal ears.
• Pulmonary hypoplasia:Pulmonary hypoplasia: The degree of pulmonary hypoplasia The degree of pulmonary hypoplasia depends on the degree and duration of oligohydramnios, as well depends on the degree and duration of oligohydramnios, as well as the stage of lung development at which oligohydramnios as the stage of lung development at which oligohydramnios occurs.occurs.
• Features of Eagle-Barrett (prune belly) syndrome:Features of Eagle-Barrett (prune belly) syndrome: This is an This is an occasional cause of the Potter syndrome. Neonates have a occasional cause of the Potter syndrome. Neonates have a deficient abdominal wall, undescended testes, dilated ureters, and deficient abdominal wall, undescended testes, dilated ureters, and a renal pelvis.a renal pelvis.
• Skeletal malformations:Skeletal malformations: Hemivertebrae, sacral agenesis, and Hemivertebrae, sacral agenesis, and limb anomalies may be present.limb anomalies may be present.
• Ophthalmologic malformationsOphthalmologic malformations: Cataract, angiomatous : Cataract, angiomatous malformation in the optic disc area, prolapse of the lens, and malformation in the optic disc area, prolapse of the lens, and expulsive hemorrhage may be present.expulsive hemorrhage may be present.
• Cardiovascular malformations:Cardiovascular malformations: Ventricular Ventricular septalseptal defect defect, , endocardial cushion defect, endocardial cushion defect, tetralogytetralogy of of FallotFallot, and, andpatentpatent ductusductus arteriosusarteriosus may be present. may be present.
ETIOLOGY ETIOLOGY PATHOGENESISPATHOGENESIS PHENOTYPEPHENOTYPE
Oligohydramnios Extrinsic mandibular Oligohydramnios Extrinsic mandibular
deformationdeformationNeurogenic hypotonia Lack of mandibularNeurogenic hypotonia Lack of mandibular exerciseexercise
Growth deficiency Intinsic mandibular Growth deficiency Intinsic mandibular RobinsequenceRobinsequence
hypoplasiahypoplasiaConnective tissue Intrinsic mandibularConnective tissue Intrinsic mandibular disorder hypoplasia and failuredisorder hypoplasia and failure of connective tissueof connective tissue penetration across palatepenetration across palate
4.Sequences and syndromes 4.Sequences and syndromes (cont.):(cont.):
Syndrome(“running together” in greek):Syndrome(“running together” in greek):A recognized pattern of cong. Abnormalities whose A recognized pattern of cong. Abnormalities whose
unique combination of features set it apart from all unique combination of features set it apart from all other patterns.other patterns.
Most dysmorphic syndromes are a constellation of Most dysmorphic syndromes are a constellation of major and minor anomalies butmajor and minor anomalies but
NO one congenital malformation is pathognomonic NO one congenital malformation is pathognomonic for specific syndrome.for specific syndrome.
Syndrome diagnosis relies on the ability of the Syndrome diagnosis relies on the ability of the clinician to detect and correctly interpret physical & clinician to detect and correctly interpret physical & developmental findings and to recognize pattern in developmental findings and to recognize pattern in them.them.
Down’s syndromeDown’s syndrome
• Most common abnormality of Most common abnormality of autosomal chromosomesautosomal chromosomes
• Trisomy 21Trisomy 21• Incidence- 1 in 600-800 live birthsIncidence- 1 in 600-800 live births• Incidence rises with advanced Incidence rises with advanced
maternal age to 1 in 20 by age 45 maternal age to 1 in 20 by age 45 yearsyears
• Affected fetuses have increased risk Affected fetuses have increased risk or spontaneous abortionor spontaneous abortion
Down’s syndrome Down’s syndrome (contd.)(contd.)- Developmental delay- Developmental delay-- Short statureShort stature-- ObesityObesity• HEENT Features HEENT Features -- Flat occiput, 3Flat occiput, 3rdrd fontanelle, fontanelle,-- Microcephaly, small midface, Microcephaly, small midface, -- Small mandible and maxillaeSmall mandible and maxillae-- Upslanting palpebral fissuresUpslanting palpebral fissures-- Epicanthal foldsEpicanthal folds-- Speckled iris (Brushfield spots)Speckled iris (Brushfield spots)
--Refractive errors and strabismusRefractive errors and strabismus- Furrowed prominent tongueFurrowed prominent tongue- High arched palateHigh arched palate-- Ear anomaliesEar anomalies-- Frequent AOMFrequent AOM- Hearing problemsHearing problems
• CVS:CVS: Congenital heart defects (50%), particularly Congenital heart defects (50%), particularly septal defects (VSD)septal defects (VSD)
• GIT: GIT: -- Duodenal/esophageal/anal atresiaDuodenal/esophageal/anal atresia-- TE fistulaTE fistula-- Hirschsprung diseaseHirschsprung disease-- Chronic constipationChronic constipation
• Musculoskeletal system: Musculoskeletal system: -- Lax joints including dysplastic hipsLax joints including dysplastic hips-- Vertebral anomaliesVertebral anomalies-- Atlantoaxial instabilityAtlantoaxial instability -- Wide gap between 1st and 2nd toesWide gap between 1st and 2nd toes
• Genitourinary system: Genitourinary system: - Cryptorchidism- Cryptorchidism• Dermatology: Dermatology: -- Simian (palmar) creaseSimian (palmar) crease-- Abnormal dermatoglyphicsAbnormal dermatoglyphics
• Hematology: Hematology: -- 1% lifetime risk of leukemia1% lifetime risk of leukemia
• Endocrine: Endocrine: -- HypothyroidismHypothyroidism
Some Clinical Features suggest a Some Clinical Features suggest a specific specific diagnosis. (pearls ofdiagnosis. (pearls of dysmorphology ):dysmorphology ):
Pursed up lips – Whistling face syndrome.Pursed up lips – Whistling face syndrome. Broad thumbs/great toes – Rubinstein Taybi Broad thumbs/great toes – Rubinstein Taybi
syndrome , Pfeiffer syndrome, Fanconi anaemia.syndrome , Pfeiffer syndrome, Fanconi anaemia. Absent clavicles – Cleidocranial dysostosis.Absent clavicles – Cleidocranial dysostosis. Heterochromia iridis – Waardenburg syndrome.Heterochromia iridis – Waardenburg syndrome. Mitten hands – Apert syndrome.Mitten hands – Apert syndrome. Inverted nipples – Congenital disorder of Inverted nipples – Congenital disorder of
glycosylation.glycosylation. Webbing of neck – Turner and Noonan Webbing of neck – Turner and Noonan
syndrome.syndrome. Eversion of the lateral third of the lower eyelid – Eversion of the lateral third of the lower eyelid –
Kabuki make-up syndrome Kabuki make-up syndrome..
APPROACH TO THE DYSMORPHIC APPROACH TO THE DYSMORPHIC CHILD CHILD
Gathering information:Gathering information:1. History:1. History: personal (family history) & personal (family history) & Pregnancy history.Pregnancy history.
2. 2. Clinical assessmentClinical assessment::
a.Visual assessment.a.Visual assessment. b. b. Measurement.Measurement. cc.Consultation.Consultation
with a Specialist in other field like, dysmorphology,with a Specialist in other field like, dysmorphology, Ophtholmology eg. Rieger syndrome Ophtholmology eg. Rieger syndrome
d.d.Camera!Camera! It plays the role of stethoscope in field of dysmorphologyIt plays the role of stethoscope in field of dysmorphology
e.e.Radiography Radiography eg.skeletal dysplasias eg.skeletal dysplasias
3.Recognizing a genetic syndrome3.Recognizing a genetic syndrome: reaching diagnosis: reaching diagnosis
Smith’s approach,Smith’s approach,Bryan D. hall’s approachBryan D. hall’s approach..
4.Laboratory evaluation4.Laboratory evaluation: like karyotyping, F.I.S.H. genetic tests. Prenatal diagnosis : like karyotyping, F.I.S.H. genetic tests. Prenatal diagnosis
4. 4. Counselling.Counselling.5. 5. Follow-up Follow-up. .
HistoryHistory
Pedigree DrawingPedigree Drawing
Three generations is required Three generations is required to be constructed.to be constructed.
The male line on the left.The male line on the left.
Roman numerals are used for Roman numerals are used for defining generation.defining generation.
Arabic numerals are used to Arabic numerals are used to indicate each individual within indicate each individual within a generation.a generation.
Personal & family historyPersonal & family history::
• Elderly mother ; Down’s syndromeElderly mother ; Down’s syndrome• Elderly father ; new autosomal dominant mutation Elderly father ; new autosomal dominant mutation
eg.Achondroplasia , marfan’s syndromeeg.Achondroplasia , marfan’s syndrome• Maternal disease ; known associated fetal Maternal disease ; known associated fetal
abnormalities eg. Maternal Diabetes with Sacral abnormalities eg. Maternal Diabetes with Sacral agenesisagenesis
• Poor social history ; alcohol ingestion, drug Poor social history ; alcohol ingestion, drug ingestioningestion
• Racial Origin ; Ellis-Van-Crevald syndrome in AMISHRacial Origin ; Ellis-Van-Crevald syndrome in AMISH• Parental Consanguinity; Autosomal recessive Parental Consanguinity; Autosomal recessive
disordersdisorders
Pregnancy historyPregnancy history• Maternal drug or, alcohol ingestionMaternal drug or, alcohol ingestion• Exposure to radiation; possible mutagenic or Exposure to radiation; possible mutagenic or
teratogenic effects.teratogenic effects.• OLIGOHYDRAMNIOS: Renal AgenesisOLIGOHYDRAMNIOS: Renal Agenesis• POLYHYDRAMNIOS : Esophageal atresia, POLYHYDRAMNIOS : Esophageal atresia,
neuromuscular disordersneuromuscular disorders• Breech presentation : neuromuscular disordersBreech presentation : neuromuscular disorders• Antenatal Ultrasound ; gives clue to diagnosisAntenatal Ultrasound ; gives clue to diagnosis• Early rupture of membranes : possible fetal Early rupture of membranes : possible fetal
compression leading to Deformationcompression leading to Deformation
Clinical assessmentClinical assessment
Visual assessmentVisual assessmentWhenever a anomaly is noted it Whenever a anomaly is noted it should be described in following should be described in following
directivedirectiveoAppropriate terminologyAppropriate terminology
oMinor or majorMinor or majoroMalformation/disruption/Malformation/disruption/
deformationdeformationoTime of onsetTime of onset
AnthropometryAnthropometry
Measurements
Measurements
Measurements
Measurements
Common Facial Common Facial MeasurementMeasurement
(1)(1) Interpupillary Interpupillary distance,distance,
(2)(2) inner canthal inner canthal distance,distance,
(3)(3) outer canthal outer canthal distance,distance,
(4)(4) interalar distance, interalar distance,(5)(5) philtral length, philtral length,(6)(6) upper lip thickness, upper lip thickness,(7)(7) lower lip lower lip
thickness,andthickness,and(8)(8) intercommisural intercommisural
distance.distance.
Primary telecanthus,secondary Primary telecanthus,secondary telecanthus, and hypertelorismtelecanthus, and hypertelorism
(A)(A)Normal interocular distance.Normal interocular distance.(B)(B)Primary telecanthus.The Primary telecanthus.The
inner canthi are far apart, inner canthi are far apart, although the outer canthi are although the outer canthi are normally spaced.normally spaced.
(C)(C)True ocular True ocular hypertolrism,both inner hypertolrism,both inner &outer canthi are abnormally &outer canthi are abnormally far apart.far apart.
(D)(D)True ocular hypertelorism True ocular hypertelorism together with secondary together with secondary telecanthus.telecanthus.
Recognition of Genetic Recognition of Genetic syndromes :syndromes :
• Gestalt Diagnosis :Gestalt Diagnosis :
some syndromes are so striking to eye that some syndromes are so striking to eye that diagnosis is made instantaneously by diagnosis is made instantaneously by general gist of pt. this is called as ‘’Gestalt general gist of pt. this is called as ‘’Gestalt diagnosis’’ .diagnosis’’ .
• for expertise in this mode one need to have for expertise in this mode one need to have vast experiencevast experience
Useful handles in Useful handles in diagnosisdiagnosis• Head: Head: abnormal hair , abnormal hair ,
Scalp defects, Scalp defects, Craniosynostosis, Craniosynostosis, Encephalocele, Encephalocele, MicrocephalyMicrocephaly
• Eyes: Eyes: Coloboma, small Coloboma, small or absent eyes, Cataractor absent eyes, Cataract
• Ears: Ears: Deafness, Deafness, malformed pinna, malformed pinna, Preauricular tags.Preauricular tags.
• Skin: Skin: white patches, white patches, pigmented patchespigmented patches
• Genitalia: Genitalia: micropenismicropenis
• MouthMouth: : cleft lip, cleft cleft lip, cleft palate , absent or palate , absent or abnormal teethabnormal teeth
• LimbsLimbs: : partial or total partial or total absence, joint absence, joint webbing ,short limb dwarfwebbing ,short limb dwarf
• Digits: Digits: syndactyly, syndactyly, polydactyly, polydactyly, arachnodactyly, arachnodactyly, brachydactyly brachydactyly
• Nails: Nails: DymorphicDymorphic
• Once handle is identified , reference Once handle is identified , reference should be made to standard should be made to standard monograms on syndromology or monograms on syndromology or computer databases.computer databases.
• These Databases are system for These Databases are system for experts and not EXPERT SYSTEMexperts and not EXPERT SYSTEM
•Enter one or more search terms.
•Use Limits to restrict your search by search field, chromosome, and other criteria.
•Use Index to browse terms found in OMIM records.
•Use History to retrieve records from previous searches, or to combine searches.
Smith’sSmith’s approachapproach•Very small stature not Very small stature not
skeletal dysplasia :skeletal dysplasia :
eg. eg. Seckel syndrome Seckel syndrome It contains It contains
• severe mental retardation,severe mental retardation,• achondroplasia,achondroplasia,• microcephaly,microcephaly,• Pancytopenia,Pancytopenia,• Cryptorchdism,Cryptorchdism,• Unsually large eyes,low set ears, small chinUnsually large eyes,low set ears, small chin
Moderate short Moderate short stature, facial +/- stature, facial +/- genitalgenitalAarskog-scott syndrome:Aarskog-scott syndrome:• X linked recessive, mother carrierX linked recessive, mother carrier• Short statureShort stature• Rounded face,widow’s peak hairline, hypertelorism, Rounded face,widow’s peak hairline, hypertelorism,
droopy eyelids(blepharoptosis), downslanting droopy eyelids(blepharoptosis), downslanting palpebral fissures, anteverted nostrils, broad palpebral fissures, anteverted nostrils, broad philthrum, underdeveloped maxillaphilthrum, underdeveloped maxilla
• Joint laxityJoint laxity• Simian crease,brachydactyly, clinodactyly, mild Simian crease,brachydactyly, clinodactyly, mild
interdigital webbinginterdigital webbing• Mild pectus excavatum Mild pectus excavatum • Shawl scrotum, undescended testisShawl scrotum, undescended testis• Inguinal herniasInguinal hernias• Mental retardationMental retardation
William syndromeWilliam syndrome
• characteristic faciescharacteristic facies: short upturned nose, : short upturned nose, flat nasal bridge, long philthrum, flat malar area, flat nasal bridge, long philthrum, flat malar area, wide mouth, full lips, dental malocclussion and wide mouth, full lips, dental malocclussion and widely spaced teeth, micrognathia, periorbital widely spaced teeth, micrognathia, periorbital fullness.fullness.
• Short statureShort stature• Stellate lacy pattern of irisesStellate lacy pattern of irises• Microcephaly , post natal failure to thriveMicrocephaly , post natal failure to thrive• Idiopathic hypercalcaemiaIdiopathic hypercalcaemia• Cardiac lesions: supravalvular aortic stenosis, Cardiac lesions: supravalvular aortic stenosis,
pulmonary stenosis, mitral regurgitationpulmonary stenosis, mitral regurgitation• Generalised hypotoniaGeneralised hypotonia
Senile like Senile like appearanceappearanceWerner syndrome (adult progeria):Werner syndrome (adult progeria):• Autosomal recessiveAutosomal recessive• Premature agingPremature aging• Typically develop normally till they reach pubertyTypically develop normally till they reach puberty• Age of onset variable, Age of onset variable, early sign is ‘lack of early sign is ‘lack of
teenage growth spurt’ teenage growth spurt’ which results in short which results in short staturestature
• Symptoms appear generally when they are Symptoms appear generally when they are in there twenties/thirtiesin there twenties/thirties
• Charecteristic Charecteristic “bird like”“bird like” facial facial appearance appears when they reach there appearance appears when they reach there thirties.thirties.
Unusual brain and or Unusual brain and or neuromuscular findingsneuromuscular findings
Acrocallousal syndrome:Acrocallousal syndrome:• Autosomal recessiveAutosomal recessive
• Carpus callosum agenesis Carpus callosum agenesis
• Post axial PolydactylyPost axial Polydactyly
• Hallux duplicationHallux duplication
• Multiple dysmorphic featuresMultiple dysmorphic features
• Motor and Mental retardationMotor and Mental retardation
Early overgrowth with Early overgrowth with associated defectsassociated defectsMarshall Smith syndromeMarshall Smith syndrome::• Accelrated skeletal maturation Accelrated skeletal maturation
usually started before birthusually started before birth• Prominent eyes, Bluish sclera, Coarse Prominent eyes, Bluish sclera, Coarse
eyebrow, Upturned noseeyebrow, Upturned nose• Accelerated osseous maturation Accelerated osseous maturation • Phalangeal abnormalities Phalangeal abnormalities • Tubular thinning of the long bones Tubular thinning of the long bones • Skull abnormalitiesSkull abnormalities
Facial defects as major Facial defects as major featurefeatureFrontonasal dysplasia syndrome (Klippel feil Frontonasal dysplasia syndrome (Klippel feil
syndrome):syndrome):• EyesEyes Hypertelorism’Lateral displacement of inner canthiHypertelorism’Lateral displacement of inner canthi• Forehead:Forehead:Widow'sWidow's peak,Defect in midline frontal bone (cranium bifidum peak,Defect in midline frontal bone (cranium bifidum
occultum)occultum)
• Nose:Varies from notched broad nasal tip,divided nostrils Nose:Varies from notched broad nasal tip,divided nostrils with hypoplasia, absence of prolabium and premaxilla with with hypoplasia, absence of prolabium and premaxilla with cleft lip,Broad nasal roo,Lack of formation of nasal tipcleft lip,Broad nasal roo,Lack of formation of nasal tip
• Occassional abnormalitiesOccassional abnormalities– Accessory nasal tagsAccessory nasal tags– Anomalies of optic disk, optic nerve, retina, or eye Anomalies of optic disk, optic nerve, retina, or eye
(colobomas, cataracts)(colobomas, cataracts)– Preauricular tags, low-set earsPreauricular tags, low-set ears– Conductive deafnessConductive deafness– Mental deficiency (8-20%)Mental deficiency (8-20%)– Frontal cutaneous lipoma or lipoma of corpus callosumFrontal cutaneous lipoma or lipoma of corpus callosum– Agenesis of corpus collosumAgenesis of corpus collosum– Anterior basal encephaloceleAnterior basal encephalocele– Tetralogy of FallotTetralogy of Fallot– Cleft lip and/or cleft palateCleft lip and/or cleft palate
Facial limb defects as major Facial limb defects as major featurefeature
Hay-wells syndrome:Hay-wells syndrome:• Ankyloblepharon filiforme adanatumAnkyloblepharon filiforme adanatum• Hair are coarse and sparseHair are coarse and sparse• Eyelashes are sparse or absentEyelashes are sparse or absent• Nails are absent or malformedNails are absent or malformed• Hypohidrosis; fewer than normal sweat glandsHypohidrosis; fewer than normal sweat glands• Chronic dermatitis of scalpChronic dermatitis of scalp• Bilateral cleft lip and cleft palateBilateral cleft lip and cleft palate• Broad nasal bridgeBroad nasal bridge• Supernumerary nipplesSupernumerary nipples
Limb defects as major Limb defects as major featurefeature
Femoral hypoplasia (unusual Femoral hypoplasia (unusual facies syndrome):facies syndrome):
• Short broad tipped noseShort broad tipped nose
• Long philtrumLong philtrum
• Thin upper lip, Micrognathia, Cleft Thin upper lip, Micrognathia, Cleft palatepalate
• Underdeveloped femurUnderdeveloped femur
Craniosynostosis Craniosynostosis syndromessyndromesApert syndrome:Apert syndrome:• AcrocephalysyndactylyAcrocephalysyndactyly• Brachiocephaly, high prominent Brachiocephaly, high prominent
forehead, flat posterior skullforehead, flat posterior skull• Mental retardation due to premature Mental retardation due to premature
closure of coronal suturesclosure of coronal sutures• Syndactyly of hands and feetSyndactyly of hands and feet• Synonychia fusion of two or more Synonychia fusion of two or more
nails of digitsnails of digits
Bryan D. Hall approachBryan D. Hall approach
• This approachThis approach is helpful in cases of skeletal is helpful in cases of skeletal dysplasiadysplasia
• 1) Diagnosing short stature1) Diagnosing short stature
• 2) Diagnosing disproportionate short stature2) Diagnosing disproportionate short stature
• 3) diagnosing what causes this Disproportion, 3) diagnosing what causes this Disproportion,
-is it short trunk?-is it short trunk?
Eg.spondyloepiphyseal dysplasiaEg.spondyloepiphyseal dysplasia
-is it short limbs? Eg.achondroplasia? -is it short limbs? Eg.achondroplasia?
• 4) if short limbed which part of the Limbs 4) if short limbed which part of the Limbs are affected-are affected-
a) Rhizomelia- proximal shortening i.e. a) Rhizomelia- proximal shortening i.e. humerus and femur eg.chondrodysplasia humerus and femur eg.chondrodysplasia punctatapunctata
b) Mesomelia- shortening of middle segment b) Mesomelia- shortening of middle segment i.e.radius,ulna,tibia,fibulai.e.radius,ulna,tibia,fibula
c)Acromelia- distal shortening i.e. hands and c)Acromelia- distal shortening i.e. hands and foot e.g. acromesomelic dysplasiafoot e.g. acromesomelic dysplasia
d) Combinations- Ellis van crevald syndrome, d) Combinations- Ellis van crevald syndrome, achondroplasia achondroplasia
5) Diagnosing deformations caused by 5) Diagnosing deformations caused by osseous abnormalities-eg.craniosynostosisosseous abnormalities-eg.craniosynostosis
• 6) Based on areas involved 6) Based on areas involved radiologicallyradiologically
• A)Epiphyseal dysplasiaA)Epiphyseal dysplasia
• B)Diaphyseal dysplasiaB)Diaphyseal dysplasia
• C)Metaphyseal dysplasiaC)Metaphyseal dysplasia
• E)Spine involvementE)Spine involvement
• F)Cranial involvementF)Cranial involvement
• G)Hand involvementG)Hand involvement
• Based on clinical & radiological Based on clinical & radiological groundground
• 1) Pure skeletal dysplasia; 1) Pure skeletal dysplasia; achondroplasiaachondroplasia
• 2) Malformation associated; 2) Malformation associated; Stickler syndromeStickler syndrome
• 3) Malformation/ Mental 3) Malformation/ Mental retardation; campomelic dysplasiaretardation; campomelic dysplasia
INVESTIGATIONSINVESTIGATIONS
(A)Karyotyping(A)Karyotyping:: high resolution high resolution karyotype i.e. chromosomal analysis , it karyotype i.e. chromosomal analysis , it is definitive diagnostic test for is definitive diagnostic test for aneuploidy like Down’s syndrome, aneuploidy like Down’s syndrome, Turner syndrome.Turner syndrome.
(B)Fluorescent In-situ Hybridization (B)Fluorescent In-situ Hybridization (FISH):(FISH): this technique has revolutionized this technique has revolutionized field of cytogenetics. It can attach specific field of cytogenetics. It can attach specific locus on a chromosomes bring to light locus on a chromosomes bring to light microdeletions that are not visible in standard microdeletions that are not visible in standard karyotype.karyotype.
..
INVESTIGATIONS,INVESTIGATIONS,(cont.)(cont.)
(C) Imaging studies(C) Imaging studies , both conventional , both conventional & MRI. & MRI.
(D) Echocardiography(D) Echocardiography..
(E) Metabolic studies.(E) Metabolic studies.
Prenatal diagnosisPrenatal diagnosis
• It is determination of the status of It is determination of the status of the fetus by variety of techniques like the fetus by variety of techniques like chromosomal, biochemical,DNA, using chromosomal, biochemical,DNA, using variety of procedures like:variety of procedures like:
• Chorionic villus sampling ;8-11 weeksChorionic villus sampling ;8-11 weeks
• Amniocentesis: 11-16 weeksAmniocentesis: 11-16 weeks
• Blood analysis by CHORDOCENTESIS, Blood analysis by CHORDOCENTESIS, FETOSCOPY,EMBRYOSCOPYFETOSCOPY,EMBRYOSCOPY
Copyright © 2006 by the American Roentgen Ray Society
Smith, A. S. et al. Am. J. Roentgenol. 2004;183:229-235
Prenatal ultrasonography Unilateral incomplete cleft lip in fetus at 34 weeks'
gestation
Recent advancesRecent advances
• 3 D face shape modelling: 3 D face shape modelling: this is a this is a new modality of three dimensional models new modality of three dimensional models of facial morphology is showing potential in of facial morphology is showing potential in objective syndrome delineation and objective syndrome delineation and discriminationdiscrimination
3D Facial Photographs.3D Facial Photographs.
Behavioral phenotypeBehavioral phenotype
• Unique behaviour associated with Unique behaviour associated with specific syndrome:specific syndrome:
• Friendly social nature in William Friendly social nature in William syndromesyndrome
• Tendency to over eat in prader-willi Tendency to over eat in prader-willi syndromesyndrome
• Selfmutilating & destructive in Lesch-Selfmutilating & destructive in Lesch-Nyhan syndromeNyhan syndrome
• Autistic behaviour in Fragile-X syndromeAutistic behaviour in Fragile-X syndrome• Happy nature in Angelman syndromeHappy nature in Angelman syndrome
Reaching a diagnosisReaching a diagnosis::
Fast recall of the facial gestalt.Fast recall of the facial gestalt.Select few pivotal features or Select few pivotal features or
diagnostic handles from hx. & exam.diagnostic handles from hx. & exam.Prioritizing the featurePrioritizing the featureConsult textbooks or search Consult textbooks or search
engines.engines.POSSUM , LDDB , OMIM .POSSUM , LDDB , OMIM .Case reports.Case reports.
APPROCH TO THE DYSMORPHIC APPROCH TO THE DYSMORPHIC CHILD CHILD
Counseling:Counseling:
1.1. Counsel the parents together.Counsel the parents together.
2.2. Remove distractions.Remove distractions.
3.3. Be prepared to repeat.Be prepared to repeat.
4.4. Use visual aids.Use visual aids.
5.5. Ascertain what the family needs.Ascertain what the family needs.
APPROACH TO THE DYSMORPHIC APPROACH TO THE DYSMORPHIC CHILDCHILD
Follow – up:Follow – up:
Lack of diagnosis.Lack of diagnosis.
Counseling other family members.Counseling other family members.
New diagnostic technique.New diagnostic technique.
Natural history.Natural history.
SuspicionSuspicion Congenital abnormalitiesCongenital abnormalities Growth problemsGrowth problems Mental deficitMental deficit
AnalysisAnalysis HistoryHistory PedigreePedigree Family Family Pregnancy & BirthPregnancy & Birth HealthHealth Growth & DevelopmentGrowth & Development
Previous laboratory and X-ray Previous laboratory and X-ray studiesstudies
Physical examinationPhysical examination Anatomic regionsAnatomic regions Organ systemsOrgan systems MeasurementsMeasurements PhotographsPhotographs
Laboratory testsLaboratory testsX-ray studiesX-ray studiesOtherOther Family investigationsFamily investigations Watchful waitingWatchful waiting
SynthesisSynthesis “ “ Pivotal “ findingsPivotal “ findings Pattern recognitionPattern recognition Comparison with known casesComparison with known cases Personal experiencePersonal experience LiteratureLiterature
ConfirmationConfirmation LaboratoryLaboratory Clinical courseClinical course Birth of affected relativesBirth of affected relatives
InterventionIntervention TreatmentTreatment CounselingCounseling
Follow-upFollow-up
Components of the Dysmorphologic Evaluation
