Undergraduates of Medicine and Pediatrics Basics for thinking of Dysmorphology

1. Approach to diagnosis of
Malformed Infant & Child
Mohammad Al-Haggar, MD.
Professor of Genetics

2. Dysmorphology vs. IEM.
• Abnormal structure ±
abnormal function 
minor vs. major
dysmorphism
• Normal structure but
with abnormal
function  IEMs
(enzymopathy).
Structure vs. Function
M. Al-Haggar, MD.

3. History
• Pedigree  inheritance, RR.
• Parental age  maternal, paternal
• Consanguinity.
• Abortion and still birth.
• Age of presentation and course.
M. Al-Haggar, MD.

4. Nomenclature
• Congenital vs Developmental / Genetic.
• Single vs multiple  Major vs minor.
• Sequence vs Syndrome.
• Deformity.
• Malformation.
• Disruption.
• Dysplasia.
M. Al-Haggar, MD.

5. DeformationDysplasia
PACKAGINGPRODUCTION
Disruption Malformation
Extrinsic ?

6. Diagramatic Sketch
• Malformation  Production intrinsic defect 
failure of embryonic proliferation and/or
differentiation  Abnormal structure.
• Disruptions  Production extrinsic (disruptive)
agents  interferes with embryonic development of
a structure  destruction or removal of structure.
• Dysplasias  Production intrinsic defect  abnormal
cellular organization  abnormal model of structure.
• Deformation  Packaging extrinsic defect 
normally formed structure pushed out by mechanical
forces.
Production,Intrinsic
EXtrinsic

7. Flow Chart
• Number of malformation.
• Number of involved tissue.
• Presence of tissue damage.
• Presence of Joint and bone Involvement.
M. Al-Haggar, MD.

8. Algorithm for Malformed Infant
1. Number of Malformations1. Number of Malformations
2. No. of Involved tissues2. No. of Involved tissues
3. Primary Tissue Destruction3. Primary Tissue Destruction
May be minor or major
Single / IsolatedSingle / Isolated MultipleMultiple
OneOne ≥ Two≥ Two
YesYes NoNo
4. Primary Joint, Bone Involvement4. Primary Joint, Bone Involvement
YesYes NoNo

9. Dysplasia
M. Al-Haggar, MD.

10. Algorithm for Malformed Infant
1. Number of Malformations1. Number of Malformations
2. No. of Involved tissues2. No. of Involved tissues
3. Primary Tissue Destruction3. Primary Tissue Destruction
May be minor or major
Single / IsolatedSingle / Isolated MultipleMultiple
OneOne
Dysplasia
≥ Two≥ Two
YesYes NoNo
4. Primary Joint, Bone Involvement4. Primary Joint, Bone Involvement
YesYes NoNo

11. • Malformations  major, multiple.
M. Al-Haggar, MD.

12. • Malformations  major, multiple.
•Tissues involved  One (bone).
M. Al-Haggar, MD.

13. • Malformations  major, multiple.
•Tissues involved  One (bone).
•Tissue damage  Absent.
M. Al-Haggar, MD.

14. • Malformations  major, multiple.
•Tissues involved  One (bone).
•Tissue damage  Absent.
•Joints involvement  No.
Dysmorphic Short Infant with
Intact Bones & Joints
Skeletal Dysplasia
(Achondroplasia)
M. Al-Haggar, MD.

15. Disruption
M. Al-Haggar, MD.

16. Algorithm for Malformed Infant
1. Number of Malformations1. Number of Malformations
2. No. of Involved tissues2. No. of Involved tissues
3. Primary Tissue Destruction3. Primary Tissue Destruction
May be minor or major
Single / IsolatedSingle / Isolated MultipleMultiple
OneOne ≥ Two≥ Two
YesYes
Disruption Sequence
NoNo
4. Primary Joint, Bone Involvement4. Primary Joint, Bone Involvement
YesYes NoNo
M. Al-Haggar, MD.

17. M. Al-Haggar, MD.

19. • Malformations  major, multiple.
M. Al-Haggar, MD.

20. • Malformations  major, multiple.
•Tissues involved  ≥ 2 (bones, Skin, genitalia).
M. Al-Haggar, MD.

21. • Malformations  major, multiple.
•Tissues involved  ≥ 2 (bones, Skin, genitalia).
•Tissue damage  Yes (absent 1 LL = fused
LLs).
M. Al-Haggar, MD.

22. • Malformations  major, multiple.
•Tissues involved  ≥ 2 (bones, Skin, genitalia).
•Tissue damage  Yes (absent 1 LL = fused
LLs).
•Joints involvement  Absent (? Secondary).
Disruption (Vascular steal) with
2ry Deformation (AMC)
Sirenomelia
M. Al-Haggar, MD.

23. Deformation
M. Al-Haggar, MD.

24. Algorithm for Malformed Infant
1. Number of Malformations1. Number of Malformations
2. No. of Involved tissues2. No. of Involved tissues
3. Primary Tissue Destruction3. Primary Tissue Destruction
May be minor or major
Single / IsolatedSingle / Isolated MultipleMultiple
OneOne ≥ Two≥ Two
YesYes
Deformation Sequence
NoNo
4. Primary Joint, Bone Involvement4. Primary Joint, Bone Involvement
YesYes NoNo
M. Al-Haggar, MD.

25. M. Al-Haggar, MD.

26. • Malformations  Multiple
Contractures of hands, feet, face
M. Al-Haggar, MD.

27. • Malformations  Multiple
Contractures of hands, feet, face
•Tissue involved  many.
M. Al-Haggar, MD.

28. • Malformations  Multiple
Contractures of hands, feet, face
•Tissue involved  many.
•Tissue damage  Absent.
M. Al-Haggar, MD.

29. • Malformations  Multiple
Contractures of hands, feet, face
•Tissue involved  many.
•Tissue damage  Absent.
•Joints  Yes (Contractures).
Multiple 1ry Deformations 
Generalized Contractures
(DA.)
Arthrogryposis Multiplex
Congenita (AMC)
Freeman Sheldon
Syndrome (FSS)

30. Secondary Deformations
Restricted Fetal Movement
Potter’s Face
Renal Agenesis
Oligohydramnios
M. Al-Haggar, MD.

31. Malformation Syndrome
M. Al-Haggar, MD.

32. Algorithm for Malformed Infant
1. Number of Malformations1. Number of Malformations
2. No. of Involved tissues2. No. of Involved tissues
3. Primary Tissue Destruction3. Primary Tissue Destruction
May be minor or major
Single / IsolatedSingle / Isolated MultipleMultiple
OneOne ≥ Two≥ Two
YesYes NoNo
4. Primary Joint, Bone Involvement4. Primary Joint, Bone Involvement
YesYes
Malformation
or MMS
NoNo
M. Al-Haggar, MD.

33. • Malformations  major, multiple.
M. Al-Haggar, MD.

34. • Malformations  major, multiple.
•Tissues involved  ≥ 2 (bones, Sclera, Ear).
M. Al-Haggar, MD.

35. • Malformations  major, multiple.
•Tissues involved  ≥ 2 (bones, Sclera, Ear).
•Tissue damage  Absent.
M. Al-Haggar, MD.

36. • Malformations  major, multiple.
•Tissues involved  ≥ 2 (bones, Sclera, Ear).
•Tissue damage  Absent.
•Joints involvement  No.
Multiple Malformation Syndrome 
Bone fractures
Osteogenesis Imperfecta
M. Al-Haggar, MD.

37. Algorithm for Malformed Infant
1. Number of Malformations1. Number of Malformations
2. No. of Involved tissues2. No. of Involved tissues
3. Primary Tissue Destruction3. Primary Tissue Destruction
May be minor or major
Single / IsolatedSingle / Isolated MultipleMultiple
OneOne
Dysplasia
≥ Two≥ Two
YesYes
Disruption Sequence
Deformation Sequence  Fetal Akinesia Syndrome:-
1.Oligohydraminos  Renal Agenesis (Potter).
2.Myopathic / Neuropathic Athrogryposis (AMC).
NoNo
4. Primary Joint, Bone Involvement4. Primary Joint, Bone Involvement
YesYes
Malformation or MMS
NoNo

38. Exercise
M. Al-Haggar, MD.

39. • Malformations  Multiple major.
M. Al-Haggar, MD.

40. • Malformations  Multiple major.
•Tissue involved  many.
M. Al-Haggar, MD.

41. • Malformations  Multiple major.
•Tissue involved  many.
•Tissue damage  Yes.
M. Al-Haggar, MD.

42. • Malformations  Multiple major
•Tissue involved  many.
•Tissue damage  Yes.
•Joints  2ry Contractures.
Disruption
Sequence  2ry deformation =
Neuropathic AMC
M. Al-Haggar, MD.

43. Multiple Malformation Syndrome
• Diagnostic dilemma….
1.Define.
2.Investigate.
3.Analyze.
4.Grub  scientific web.
5.Enquire  Consult.
6.Search  Publication, Citation.
M. Al-Haggar, MD.

44. Diagnosis
• Investigations  relevant.
• Differential diagnosis.
• Search engines.
• No place for bedside diagnosis.
M. Al-Haggar, MD.

45. Examination
• Systematic.
• Symmetry in bilateral organs  Goldenhar,
Silver Russel.
• Genitalia  Turner, Optiz.
• Psychomotor retardation  DS, FXS.
• Ear, Eye, Hands.
M. Al-Haggar, MD.

46. Dysmorphology Pearls
• Pursed up lips.
• Heterochromia iridis.
• Eversion of lateral third of lower eyelid.
• Webbing of the neck.
• Absent clavicles.
• Inverted nipples.
• Broad thumbs / great toes.
• Radial ray defects.
• Thrombocytopenia absent radius syndrome.
• Mitten hands.
• Hyper extensibility of skin and joints.
M. Al-Haggar, MD.

47. Dysmorphology
Seckel dwarfism (AR.)  bird headed face with
prominent nose

48. Carbamazepine Teratogenesis  flat nose, long philtrum,
abnormal ears and microcephaly
1
2
3
M. Al-Haggar, MD.

49. Major malformation  NTD;
meningomyelocele,
and occipital encephalocele
Minor malformation (Polydactyly)
Postaxial  Common, isolated
malformation or part of a syndrome.
Preaxial  rare, usually syndromic.
M. Al-Haggar, MD.

50. CDG  Inverted nipples, Abnormal fat distribution, FTT, severe
developmental delay.
M. Al-Haggar, MD.

51. Ehlers Danlos (AD.)  Skin hyper-extensibility.
M. Al-Haggar, MD.

52. William syndrome  Peri-orbital edema, bilateral
epicanthic folds and thick everted lower lip, Echo  AS.
M. Al-Haggar, MD.

53. M. Al-Haggar, MD.

54. Blue are affecteds
M. Al-Haggar, MD.

55. Age of onset of blue affecteds in successive
generation).
M. Al-Haggar, MD.

56. Blue are carriers, red are affecteds
M. Al-Haggar, MD.

57. M. Al-Haggar, MD.

58. Lethal in males (incontinentia pigmenti)
M. Al-Haggar, MD.

59. Blue are affecteds
M. Al-Haggar, MD.

60. Blue are affecteds.
M. Al-Haggar, MD.

61. M. Al-Haggar, MD.