An Introduction to Dysmorphology Clinical Approach and Classification. Dr. malek nia Genetic consulting center Of welfare organization

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2 An Introduction to Dysmorphology Clinical Approach and Classification Dr. malek nia Genetic consulting center Of welfare organization

3 What are the problems? When did they happen? How did they arise? Why did they occur? What is the diagnosis? Who else is at risk? Where can the patient/family get help?

4 Classification of Observable Differences Normal variations Minor anomalies Major anomalies

5 Model for Variation in Skin Color

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7 Minor Anomaly Minor variations of normal morphological features of little of no known medical, surgical, or cosmetic significance Single minor anomalies are present in about 15% of newborns

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12 Significance of minor anomalies Occurrence of single minor anomaly Occurrence of two minor anomalies Presence of 3 or more minor anomalies 42% of idiopathic MR have 3 or more anomalies External minor anomalies in the head and neck region and the hand 15% of all newborns 3% have an associated major anomaly Less common 11% have an associated major anomaly Unusual 1% 90% have an major associated anomaly 80% of which are minor anomalies Constitutes 71% of minor anomalies

13 Major Anomaly Abnormality that has medical, surgical, or cosmetic significance

14 Major anomalies are more common in early embryos (up to 15%) than they are in newborns (3%). Most severely malformed embryos are spontaneously aborted during first 6 to 8 weeks.

15 postaxial preaxial

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18 Categorizing congenital anomalies/dysmorphic features 1. Malformation 2. Deformation 3. Disruption 4. Dysplasia

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20 Pathogenesis of congenital abnormalities 1. Deformation an abnormal mechanical force which distorts an otherwise normal structure

21 Deformation :There is normal development, but this process is acted upon by an extrinsic or intrinsic mechanical force. Extrinsic forces include multiple gestations, abnormal uterus, or oligohydramnios. Intrinsic forces include neuromuscular abnormalities, amyoplasia, or skeletal anomalies. Deformations affect approximately 2% of newborns. These anomalies have a good prognosis and are typically easy to treat with physical therapy or external fixation devices (casts or braces). Examples include: club feet

22 club foot plagiocephaly

23 Deformations due to oligohydramnios

24 Pathogenesis of congenital abnormalities 2. Disruption an abnormal structure of an organ or tissue as a result of external factors disturbing the normal developmental process include ischemia, infection or trauma These are typically isolated non-genetic events that have a low recurrence risk Example: Amniotic band syndrome Intestinal atresia caused by vascular insufficiency

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26 Disruption of lip formation due to amniotic bands

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28 Congenital ring constrictions with amniotic bands

29 Pathogenesis of congenital abnormalities 3. Malformation primary structural defect of an organ which results from an inherent abnormality in development hypoplasia, incomplete closure, incomplete separation, usually occurring before 10 weeks of gestation.

30 Malformation : There is an intrinsically abnormal developmental process, with the early development of a tissue or organ being arrested, delayed, or misdirected. These anomalies can be caused by a teratogen or abnormalities in a gene, a group of genes, or a chromosome. Major malformations are those which have medical, surgical or cosmetic significance. Examples include: cleft lip/palate, cardiac defects, and abdominal wall defects. Minor malformations are insignificant variants. Examples include: pre-auricular ear pits, hair whorls, and clinodactyly.

31 Neural Tube Defects

32 Gastroschisis

33 Omphalocele

34 Ambiguous genitalia

35 Bladder exstrophy

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38 Pathogenesis of congenital abnormalities 4. Dysplasia Error of morphogenesis due to the abnormal cellular organization of function in a specific type of tissue most often due to single gene defects, Example renal dysplasia, hemangioma, and skeletal dysplasia: Achondroplasia, ectodermal dysplasia, osteogenesis imperfecta

39 Ectodermal dysplasia

40 Achondroplasia

41 Clinical presentation of congenital Syndromes malformations Associations Sequences

42 A B Embryonic period Fetal period Death of the embryo is possible Susceptibility to abnormalities is increased Functional disorders are more likely

43 genetic etiology should be suspected Congenital anomalies (e.g major anomaly or > 2 minor anomalies) Growth deficit (e.g. short stature or failure to thrive) Developmental delay, mental deficit or developmental regression Failure to develop secondary sexual characteristics Ambiguous genitalia Funny looking kid

44 Causes of congenital anomalies

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46 Diabet Poorly controlled diabetes has been associated with an increased rate of microcephaly fetal cardiovascular, renal, and neural tube and caudal regression syndrome are seen with higher frequency than expected.

47 The rate of malformation appears be directly related to the level of fasting hyperglycemia at diagnosis. Fasting Glucose (mg/dl) Rate of Malformation < % % > %

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49 Common teratogens drugs Alcohol Anti-coagulants - Warfarin Anti-convulsants - Phynetoin, Valproic acid Antibiotics - Streptomycin/Tetracycline Psychiatric drugs - Lithium Illicit drugs - cocaine/ heroin Hormones -estrogens Isotretinoin

50 Chemical Carbon Monoxide Insecticides Mercury Organic Solvents Paint Polychlorin biphenyl Smoking

51 The evaluation of a dysmorphic child requires a systematic approach with a: detailed history careful physical examination

52 HISTORY Pregnancy history Birth history Past Medical History Developmental History Family History

53 Pregnancy history - Problems with infertility (medications [clomid], techniques [IVF - invitro fertilization, PGD - preimplantation genetic diagnosis, ICSI - intracytoplasmic sperm injection ( - Fetal Movement (active, decreased ( - Exposures (medications, tobacco, alcohol, drugs, chemicals( - Illnesses (fevers, exposures to infections ( - Problems (bleeding, pre-term labor, abnormal prenatal testing or ultrasound (

54 Presentation: breech? Birth history Delivery: vaginal, c-section (why?) Neonatal course (complications/problems and days hospitalized)

55 Past Medical History Similar to standard history (illnesses, hospitalizations, surgeries, immunizations, medications, allergies) including a detailed review of systems.

56 Developmental History Address parental concerns. Determine ages for milestones (gross motor, fine motor, personal/social, language, rolling over, sitting, walking, and talking). Determine current milestones (appropriate for age?)

57 Family History A detailed three-generation family pedigree should be obtained for all patients. The family pedigree is an essential tool that allows for the direct visualization of the relationship of physical features or conditions in order to determine inheritance patterns. The proband, who is the individual of interest, should be indicated with an arrow. Lastly, in addition to conditions or physical traits, a complete pedigree should include ages with ethnicities, and causes of death.

58 Evaluation of the dysmorphic child The evaluation of a dysmorphic child requires a systematic approach with a: detailed history careful physical examination

59 physical examination Every body part has to be examined with particular emphasis on size, shape, color, position, spacing, and symmetry. Below are some frequently used concepts and descriptions :

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63 Digital Dysmorphology Digitall face analysis Machine learning Healthy Down

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69 Growth Growth is a key and vital concept in the evaluation of all children. Measurements of the child's weight, length, and head circumference should be plotted on the standardized growth charts.

70 Head : shape pl from dolichocephaly/scapholocephaly from bracalyhyceph ( fontanel size/shape (wide, large, small), sutures (ridges, agiocephaly prominent ) Hair : color, texture, distribution (low/high hairline, whorls ) Eyes : shape (almond); palpebral fissures (length, slant), spacing (hypotelorism, hypertelorisim ) Ears : shape (box, simple), position (low-set, posteriorly rotated ) Nose : root, bridge (prominent, flat, wide), tip (bulbous, wide ) Midface : Mouth : Chin : flat, hypoplastic size, shape (down-turned, up-turned), palate (intact, cleft), teeth (wide-spaced, crowded ) small (micrognathia), prominent (prognathia), recessed (retrognathia ) Neck : length (short, long), webbed, excess skin Chest : symmetry, size, nipples: shape (inverted), spacing (wide-spaced ) Heart : Abdomen : routine exam for rate, rhythm and murmurs hepatosplenomegaly, hernias

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73 Suture Growth Sutures allow growth perpendicular to them Growth at suture lines related to brain growth

74 Early Closure Causes Growth Parallel to the Suture

75 Sagittal Synostosis Boat-Head (Scaphocephaly)

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78 Coronal Synostosis Bent-Head (Plagiocepahly)

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80 Metopic Synostosis Triangle-Head (Trigonocephaly)

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84 Microcephaly

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87 Hydrocephalus 87

88 2 months old male, noted at birth to have a big head

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91 Head : from brachycephaly ( shape from dolichocephaly/scapholocephaly,capp from CAPP), fontanel size/shape plagiocephaly (wide, large, small), sutures (ridges, prominent ) Hair : color, texture, distribution (low/high hairline, whorls ) Eyes :,MyPACS shape (almond); palpebral fissures (length, slant), spacing (hypotelorism, hypertelorisim ) Ears : shape (box, simple), position (low-set, posteriorly rotated ) Nose : root, bridge (prominent, flat, wide), tip (bulbous, wide ) Midface : Mouth : Chin : Neck : Chest : Heart : Abdomen : flat, hypoplastic size, shape (down-turned, up-turned), palate (intact, cleft), teeth (wide-spaced, crowded ) small (micrognathia), prominent (prognathia), recessed (retrognathia ) length (short, long), webbed, excess skin symmetry, size, nipples: shape (inverted), spacing (wide-spaced ) routine exam for rate, rhythm and murmurs hepatosplenomegaly, hernias

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98 Receding anterior hair line with hair hypopigmentation Silver colored hair

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101 Head : from brachycephaly ( shape from dolichocephaly/scapholocephaly,capp from CAPP), fontanel size/shape plagiocephaly (wide, large, small), sutures (ridges, prominent ) Hair : color, texture, distribution (low/high hairline, whorls ) Eyes :,MyPACS shape (almond); palpebral fissures (length, slant), spacing (hypotelorism, hypertelorisim ) Ears : shape (box, simple), position (low-set, posteriorly rotated ) Nose : root, bridge (prominent, flat, wide), tip (bulbous, wide ) Midface : Mouth : Chin : Neck : Chest : Heart : Abdomen : flat, hypoplastic size, shape (down-turned, up-turned), palate (intact, cleft), teeth (wide-spaced, crowded ) small (micrognathia), prominent (prognathia), recessed (retrognathia ) length (short, long), webbed, excess skin symmetry, size, nipples: shape (inverted), spacing (wide-spaced ) routine exam for rate, rhythm and murmurs hepatosplenomegaly, hernias

102 Hypertelorism Zellweger Syndrome

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104 Hypotelorism distal duplication 14p

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106 Palpebral slant Upslant downslant

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108 Blephrophimosis Unilateral microphthalmia Unilateral anophthalmia Bilateral anophthalmia

109 Corneal opacity Heterochromia Squint Congenital glaucoma

110 Cataract Epibulbar dermoid Bilateral ptosis of eyelids Microphtalmia

111 Microphthalmia Coloboma

112 Head : from brachycephaly ( shape from dolichocephaly/scapholocephaly,capp from CAPP), fontanel size/shape (wide, plagiocephaly large, small), sutures (ridges, prominent ),MyPACS Hair : color, texture, distribution (low/high hairline, whorls ) Eyes : shape (almond); palpebral fissures (length, slant), spacing (hypotelorism, hypertelorisim ) Ears : shape (box, simple), position (low-set, posteriorly rotated ) Nose : root, bridge (prominent, flat, wide), tip (bulbous, wide ) Midface : Mouth : Chin : Neck : flat, hypoplastic size, shape (down-turned, up-turned), palate (intact, cleft), teeth (wide-spaced, crowded ) small (micrognathia), prominent (prognathia), recessed (retrognathia ) length (short, long), webbed, excess skin Chest : symmetry, size, nipples: shape (inverted), spacing (wide-spaced ) Heart : Abdomen : routine exam for rate, rhythm and murmurs hepatosplenomegaly, hernias

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114 Preauricular skin tags

115 Hypoplastic ear

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117 Microtia

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123 Low Set

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128 Angulation of the Auricle Vertical Plane of head Horizontal plane Longest Diameter Protrusion

129 Head : from brachycephaly ( shape from dolichocephaly/scapholocephaly,capp from CAPP), fontanel size/shape plagiocephaly (wide, large, small), sutures (ridges, prominent ) Hair : color, texture, distribution (low/high hairline, whorls ) Eyes :,MyPACS shape (almond); palpebral fissures (length, slant), spacing (hypotelorism, hypertelorisim ) Ears : shape (box, simple), position (low-set, posteriorly rotated ) Nose : root, bridge (prominent, flat, wide), tip (bulbous, wide ) Midface : Mouth : Chin : Neck : Chest : Heart : Abdomen : flat, hypoplastic size, shape (down-turned, up-turned), palate (intact, cleft), teeth (wide-spaced, crowded ) small (micrognathia), prominent (prognathia), recessed (retrognathia ) length (short, long), webbed, excess skin symmetry, size, nipples: shape (inverted), spacing (wide-spaced ) routine exam for rate, rhythm and murmurs hepatosplenomegaly, hernias

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133 Nose Short or long nose (the nose is usually 2/3 3/4 the length of the distance between the nasal bridge and the upper lip) Long nose Short nose Heminasal aplasia

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135 Head : from brachycephaly ( shape from dolichocephaly/scapholocephaly,capp from CAPP), fontanel size/shape plagiocephaly (wide, large, small), sutures (ridges, prominent ) Hair : color, texture, distribution (low/high hairline, whorls ) Eyes :,MyPACS shape (almond); palpebral fissures (length, slant), spacing (hypotelorism, hypertelorisim ) Ears : shape (box, simple), position (low-set, posteriorly rotated ) Nose : root, bridge (prominent, flat, wide), tip (bulbous, wide ) Midface : Mouth : Chin : Neck : Chest : Heart : Abdomen : flat, hypoplastic size, shape (down-turned, up-turned), palate (intact, cleft), teeth (wide-spaced, crowded ) small (micrognathia), prominent (prognathia), recessed (retrognathia ) length (short, long), webbed, excess skin symmetry, size, nipples: shape (inverted), spacing (wide-spaced ) routine exam for rate, rhythm and murmurs hepatosplenomegaly, hernias

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138 Aarskog Syndrome (Faciogenital dysplasia) Widow s Peak Small nose Chin crease Hypertelorism Long philtrum carp mouth

139 Head : from brachycephaly ( shape from dolichocephaly/scapholocephaly,capp from CAPP), fontanel size/shape plagiocephaly (wide, large, small), sutures (ridges, prominent ) Hair : color, texture, distribution (low/high hairline, whorls ) Eyes :,MyPACS shape (almond); palpebral fissures (length, slant), spacing (hypotelorism, hypertelorisim ) Ears : shape (box, simple), position (low-set, posteriorly rotated ) Nose : root, bridge (prominent, flat, wide), tip (bulbous, wide ) Midface : Mouth : Chin : Neck : Chest : Heart : Abdomen : flat, hypoplastic size, shape (down-turned, up-turned), palate (intact, cleft), teeth (wide-spaced, crowded ) small (micrognathia), prominent (prognathia), recessed (retrognathia ) length (short, long), webbed, excess skin symmetry, size, nipples: shape (inverted), spacing (wide-spaced ) routine exam for rate, rhythm and murmurs hepatosplenomegaly, hernias

140 Score lip and philtrum separately Significant dysmorphology Normal

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154 Head : from brachycephaly ( shape from dolichocephaly/scapholocephaly,capp from CAPP), fontanel size/shape plagiocephaly (wide, large, small), sutures (ridges, prominent ) Hair : color, texture, distribution (low/high hairline, whorls ) Eyes :,MyPACS shape (almond); palpebral fissures (length, slant), spacing (hypotelorism, hypertelorisim ) Ears : shape (box, simple), position (low-set, posteriorly rotated ) Nose : root, bridge (prominent, flat, wide), tip (bulbous, wide ) Midface : Mouth : Chin : Neck : Chest : Heart : Abdomen : flat, hypoplastic size, shape (down-turned, up-turned), palate (intact, cleft), teeth (wide-spaced, crowded ) small (micrognathia), prominent (prognathia), recessed (retrognathia ) length (short, long), webbed, excess skin symmetry, size, nipples: shape (inverted), spacing (widespaced ) routine exam for rate, rhythm and murmurs hepatosplenomegaly, hernias

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158 Skeletal Class III, concave profile Source: Dr. Wisanu Charoenkul

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161 Micrognathia Retrognathia Hypoplasia of malar region

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