EVALUATION OF A CHILD WITH DYSMORPHIC FEATURES

1. Approach to
a child with dysmorphism
Dr. Syeda Ismat Bukhari

2. Introduction
 The term dysmorphic is derived from the Greek words “dys”
(disordered, abnormal, painful) and “morph” (shape, form).
 Dysmorphology is a discipline of clinical genetics that studies and
attempts to interpret the patterns of human growth and structural
defects.

3. Dysmorphism Vs Syndrome
 The child with dysmorphic signs often does not have a major
malformation, and he or she may simply have an appearance that is
unusual compared with the general population and out of keeping
with that of unaffected close relatives.
 A syndrome is simply a recognizable pattern of dysmorphic signs that
have a common cause.

4. Understand the difference
 Major malformation
with medical +/- social implications
often require surgical repair
 Minor malformation
are of cosmetic significance sometimes
 Normal variants

5. Incidence
 Major congenital anomalies
At birth  2 – 3 %
At 5 yrs  4 – 6 %
 Minor congenital anomalies
At birth  15 %

6. The importance of recognizing minor anomalies
 Minor anomalies are often
indicators for relevant major
anomalies.

8. Causes of malformations
Cause Percent incidence
Genetic
Chromosome
Single gene
15 – 25
10 – 15
2 – 10
Multifactorial 20 – 25
Environmental
Maternal diseases
Uterine / Plazental
Drug / Chemicals
8 – 12
6 – 8
2 – 3
0.5 – 1
Twinning 0.5 – 1
Unknown 40 – 60

9. History of intrauterine development

10. Periods of malformation

12. Clinical approach

13. History
 Antenatal 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)
 Birth history
 Presentation: breech/cephalic/oblique
 Delivery: vaginal, c-section (why?)
 Neonatal course (complications/problems and days hospitalized)

14. History
 Neonatal status
 APGAR
 Anthopometric measurements
 Resuscitation
 Newborn course
 Feeding
 Activity
 Obvious deformities
 Complications / issues

15. History
 Past Medical History
 Illnesses, hospitalizations, surgeries, immunizations, medications,
allergies
 A detailed review of systems.
 Developmental History
 Address parental concerns.
 Determine ages for milestones (gross motor, fine motor,
personal/social, language).
 Determine current milestones (appropriate for age?).

16. Family history
 Take a detailed, three-generation family history

17. Family history
Ask for:
 Birth defects
 Other genetic diseases
 Multiple miscarriages
 Parental ages and health status
 Consanguinity and geographic origin

18. Physical examination
 Growth monitoring
 Measurements of the child's weight, length, and head
circumference should be plotted on the standardized
growth charts.
 General appearance
 Body shape and size etc.

19. Physical examination

20. Investigations
 Cytogenetics is a mainstay of diagnosis in dysmorphology.
 However, chromosome studies are labour intensive and relatively
expensive.
 To be visible, a chromosome deletion or duplication probably
involves at least 3–4 kilobases of DNA10 (perhaps 15–30 genes,
depending upon the location and the chromosome).

21. Fluorescence in situ hybridization (FISH)
 Prader-Willi syndrome
 Angelman syndrome
 Smith-Magenis syndrome
 Miller-Dieker syndrome
 Velo-cardio-facial syndrome
 DiGeorge syndrome

22. Whole chromosome painting (WCP)
 WCP is very useful for identifying the origin of additional
chromosome material that is microscopically visible but not
distinctive enough to be assigned to a specific chromosome.
 It can also be used to search for light microscopically invisible
(cryptic) translocations where suspicion of a chromosome
abnormality remains, despite a normal standard karyotype.
 The exchange of similarly sized and banded material between 2
chromosomes, which is not visible in a standard study, becomes
visible because of the exchange of different colours.

23. Other investigations
 Molecular (DNA) diagnostics
 Biochemical lab testing (to rule out any inborn error of metabolism,
storage diseases etc.)

24. The major problems of morphogenesis

25. Disruptions
 Morphological alterations of structures after formation
 Has low recurrence risk

26. Causes of disruption
 Ionization (x-ray, radioactive substance exposure)
 Hyperthermia
 Infections
 Teratogenic
 Metabolic
 Vascular disruption
 Amnion rupture sequence

28. Deformations
 Due to mechanical forces that mold a
part of fetus over a prolonged time
period
 The musculoskeletal system may be
involved, but may also be reversible
post-natally

29. Breech presentation

30. Risks for fetal constraint
 Maternal risk factors
 Primigravida
 Small uterus
 Uterine malformation
 Uterine fibromata
 Small maternal pelvis
 Fetal risk factors
 Oligohydroamnios
 Large fetus
 Multiple gestation

31. Deformations related to breech presentation

32. Malformations

33. Disorders of lymphatic drainage

35. Cleft palate

36. Telecantus, hyper-/hypo-telorsim

37. Ear defects

41. Chin

42. Digit anomalies

50. Non-disjunction syndromes

51. Down syndrome (trisomy 21)
 Low set ears
 Hypotonia
 Simian crease
 Wide space between first and
second toe
 Flat face

52. Patau syndrome (trisomy 13)
 Holoprosencephaly
 Cutis aplasia
 Microcephaly
 Microphthalmia
 Cleft lip +/- palate
 Polydactyly
 Congenital heart defect

53. Edwards syndrome (trisomy 18)
 Weak cry
 Polyhydroamnios
 Growth deficiency
 Low-set, malformed
auricles
 Clenched hand with
overlapping fingers
 Rocker bottom feet
 Congenital heart defect

54. Klinefelter syndrome (47xxy)
 Tall stature
 Behavioral issues
 Post-pubertal
hypogonadism

55. Turner syndrome (45x)
Not diagnosed until 5-6
yrs
 Webbed neck
 Shield chest
 Cubitus vulgaris
 Low hairline
 Short stature
 Renal anomalies
 Cardiac anomalies
(bicuspid aortic valve
and coarctation of
aorta)

56. Microdeleteions

57. Wolf hirshorn (4p)
 Hypertelorism
 Broad nasal bridge
 Cleft lip +/- palate
 Down turned mouth
 Severe mental retardation

58. Cri-du-chat (5p)
 Microcephaly
 Growth retardation
 High-pitched cat-like cry
 Congenital heart disease
 Hypotonia

59. Contiguous gene
syndrome

60. Prader-willi syndrome (15q11)
 Obesity
 Hypotonia
 Small hands and feet
 Upward slanting
palpebral fissures
 IQ : 60 – 70
 Micro-penis /
cryptorchidism

61. Angelman syndrome (15q11)
 Mental retardation
 Puppet like gait
 Paroxysms of inappropriate laughter
 Absent / limited speech
 Seizures

62. 22q11 deletion syndromes
(Di-George, Velocardial-facial, Sprintzen)
 Micrognathia
 Low set ears
 Short palpebral fissures
 Blunted nose
 High-arched palate
 Cleft palate +/- bifid uvula

63. Autosomal dominant syndromes

64. Achondroplasia (FGFR3)
 Rhizomelic shortening of
limbs
 Short fingers held in trident
configuration
 Elarged head with depressed
nasal bridge

65. Neurofibromatosis
 > 6 café-au-lait spots
 >2 neurofibromas
 Lisch nodules (iris hematoma)
 Optic gliomas
 Angiofibromas
 Axillary or inguinal freckling

66. Osteogenesis imperfecta
 Fractures
 Osteopenia
 Blue sclera
 Hearing loss
 Short stature
 Four types

67. Autosomal recessive
Cystic fibrosis
Tay-Sacs disease
Sickle cell anemia

68. Teratogens

69. Fetal alcohol syndrome

70. Quiz

71. What are the most appropriate genetic condition
associated with the following physical findings?
 Webbed neck
 Macrosomia
 Rhizometric shortening
 Small hands
 Café-au-lait spots

72. What are the most appropriate genetic condition
associated with the following physical findings?
 Upward slanting palpebral fissures
 Downward slanting palpebral fissures
 Lich nodules
 Kayser-fleischer ring

73. Thank you