CLINICAL APPROACH TO THE DYSMORPHIC CHILD

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CLINICAL APPROACH TO THE DYSMORPHIC CHILD
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Dysmorphology

• Coined by Dr.David Smith in the 1960s to describe
  the study of human congenital malformation.
• It encompass the variability of normal physical
  trait as well as pathologic features resulting
  from abnormal development.

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Accurate diagnosis

• Allow for decision making and communicating in
  the followings-
• Prognosis.
• Treatment options.
• Occult abnormalities.
• Recurrence risk.
• Pathogenesis.
• Natural Hx.

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Pre-natal vs. Post-natal onset of developmental
problems

• Pre-natal
• Alteration of pregnancy
• Gestational timing , onset nature of fetal
  activity ,and amount of amniotic fluid.
• Alteration noted at birth
• Increased incidence of breech presentation.
• Prenatal onset of growth deficiency.
• Difficulty with neonatal adaptation.

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SINGLE PRIMARY DEFECT IN DEVELOPMENT

• Subcategorized according to the nature of error
  in morphogenesis which can be helpful to
  prognosis.
• 4 modes of pathogenesis for birth defects in
  humans.
• Deformation.
• Disruption.
• Dysplasia.
• Malformation.

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SINGLE PRIMARY DEFECT IN DEVELOPMENT (cont.)

• Malformation.
• Term used for permanent changes produced by an
  intrinsic abnormality of development in a body
  structure during prenatal life.
• The actual mechanism is unknown but many involved
  error in embryonic cell proliferation,
  differentiation , migration, programmed death
  as well as cell to cell communication.
• e.g.. Pyloric stenosis.
• Cardiac septal defect.

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SINGLE PRIMARY DEFECT IN DEVELOPMENT (cont.)

• Deformation.
• Those anomalies caused by unusual mechanical
  pressure on the developing fetus usually during
  the last trimester of gestation.
• Mechanical stress may be either extrinsic or
  intrinsic.
• Recurrence risk is low.

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SINGLE PRIMARY DEFECT IN DEVELOPMENT (cont.)

• Dysplasia.
• Structural defects resulting from abnormal
  cellular organization or function that affect one
  general tissue throughout the body.
• Tissue dysplasia tend to persist or even worsen
  with age.
• Prognosis depend on the natural hx. Of the disease

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SINGLE PRIMARY DEFECT IN DEVELOPMENT (cont.)

• Disruption.
• Affect structures that had been undergoing normal
  development growth in utero.
• Usually it is local adjacent structure are
  often normal.
• Caused by severe mechanical stress Amniotic band
  , Viral infections , Tissue ischemia.
• Patients usually have the potential for normal
  intellectual development physical growth.
• Most are sporadic , rec.risk is v.low.

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Malformation
Deformation
Disruption
Interrelationships between malformations,deformati
ons,and disruptions
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• ETIOLOGY PATHOGENESIS PHENOTYPE
• Oligohydramnios Extrinsic
  mandibular
  
• 
  deformation
• Neurogenic hypotonia Lack of mandibular
• 
  exercise
• Growth deficiency Intinsic
  mandibular Robin
  sequence
• 
  hypoplasia
• Connective tissue Intrinsic
  mandibular
• disorder
  hypoplasia and failure
• 
  of connective tissue
• 
  penetration across palate

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Syndromes associated with Robins sequence
N.B 17 of Pierre Robin sequence is isolated
non-syndromic  
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• ETIOLOGY PATHOGENESIS
  PHENOTYPE
• Autosomal dominanant Mesenchymal blastoma
• gene
• Hyperthyrodism Accelerated osseous
  Crainosynstosis
• maturation
• Microcephaly Lack of growth stretch
• across sutures

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Types of Birth Defects

• Major vs. Minor abnormalities.
• Isolated vs. Multiple anomalies.
• Associations Complexes.
• Sequences Syndromes.

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1.Major vs. Minor anomalies

• Major malformations.
• Those that have medical /or social
  implications. Often require surgical repair.
• Minor malformations.
• Have Mostly cosmetic significance.
• Normal variants.

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2.Isolated vs. Multiple Anomalies

• Most are isolated affecting a single body site.
• 2/3 of the major defect are isolated ,
• and of multifactorial inheritance with
  increased frequency in some families racial
  groups.

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3.Associations and complexes

• Association
• Non-random combination of anomalies in which the
  individual component occurs together more
  frequently than would be expected by chance and
  arent enough to justify definition as a
  syndrome.
• e.g.. VACTERAL , CHARGE , MURCS .
• The recurrence risk is extremely low
• Prognosis depends on the lesions

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3.Associations and complexes (cont.)

• Complex
• Anomalies of several different structure all of
  which lie together in the same local body region
  during embryonic development.
• e.g. Poland anomaly , Sacral agenesis.

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4.Sequences and syndromes

• Sequence
• A single underlying abnormality give rise is
  a cascade of structural changes that might seem
  to be unrelated to each other ( Field- defect).
• Original defect is malformation. e.g..NTD
  sequence, Potter oligohydramion sequence.
• Disruption sequence (Amniotic band).
• Deformation sequence.

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4.Sequences and syndromes (cont.)

• Syndrome
• A recognized pattern of cong. Abnormalities whose
  unique combination of features set it apart from
  all other patterns.
• NO one congenital malformation is pathognomonic
  for specific syndrome.
• Syndrome diagnosis relies on the ability of the
  clinician to detect and correctly interpret
  physical developmental findings and to
  recognize pattern in them.

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• Some Clinical Features suggest a specific
  diagnosis. (pearls of dysmorphology )
• Pursed up lips Whistling face syndrome.
• Broad thumbs/great toes Rubinstein Taybi
  syndrome ,
• Pfeiffer syndrome.
• Fanconi anaemia.
• Absent clavicles Cleidocranial
  dysostosis.
• Heterochromia iridis Waardenburg
  syndrome.
• Mitten hands Apert syndrome.
• Inverted nipples Congenital disorder of
  glycosylation.
• Webbing of neck Turner and Noonan
  syndrome.
• Eversion of the lateral third of the lower
  eyelid Kabuki make-up
  syndrome.

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APPROACH TO THE DYSMORPHIC CHILD

• Gathering information
• Constructing the pedigree and analysis of the
  pedigree.
• Reviewing Past records and Prenatal history.
• Clinical assessment
• a.Visual assessment.
• b. Measurement.
• c. Extended Family.
• 4. Counseling.
• 5. Follow-up.

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Pedigree Drawing

• Three generations is required to be constructed.
• The male line on the left.
• Roman numerals are used for defining generation.
• Arabic numerals are used to indicate each
  individual within a generation.

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Measurements
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Measurements
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Measurements
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Measurements
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Common Facial Measurement

• (1) Interpupillary distance,
• (2) inner canthal distance,
• (3) outer canthal distance,
• (4) interalar distance,
• (5) philtral length,
• (6) upper lip thickness,
• (7) lower lip thickness,and
• (8) intercommisural distance.

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Primary telecanthus,secondary telecanthus, and
hypertelorism

• (A)Normal interocular distance.
• (B)Primary telecanthus.The inner canthi are far
  apart, although the outer canthi are normally
  spaced.
• (C)True ocular hypertolrism,both inner outer
  canthi are abnormally far apart.
• (D)True ocular hypertelorism together with
  secondary telecanthus.

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3D Facial Photographs.
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Reaching a diagnosis

• Fast recall of the facial gestalt.
• Select few pivotal features or diagnostic handles
  from hx. exam.
• Prioritizing the feature
• Consult textbooks or search engines.
• POSSUM , LDDB , OMIM .
• Case reports.

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• 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.

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INVESTIGATIONS

• (A) Chromosomal analysis
• 1. Presence of a typical defined
  chromosomal disorder.
• 2. Presence of four features- MR,
  physical retardation ,
  
  malformation and dysmorphogenesis in
  a child.
• 3. Features of two or more syndromes
  in one pt. To exclude contiguous gene syndrome.
• 4. Malformation known to have a high
  association with a chromosomal
  disorder e.g. holoprosencephaly.
• 5. Child with non-specific dysmorphism
  without a specific diagnosis.

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INVESTIGATIONS,(cont.)

• (B) Imaging studies , both conventional MRI.
• (C) Echocardiography.
• (D) Metabolic studies.

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APPROCH TO THE DYSMORPHIC CHILD

• Counseling
• Counsel the parents together.
• Remove distractions.
• Be prepared to repeat.
• Use visual aids.
• Ascertain what the family needs.

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APPROACH TO THE DYSMORPHIC CHILD

• Follow up
• Lack of diagnosis.
• Counseling other family members.
• New diagnostic technique.
• Natural history.

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Components of the Dysmorphologic Evaluation

• Suspicion
• Congenital abnormalities
• Growth problems
• Mental deficit
• Analysis
• History
• Pedigree
• Family
• Pregnancy Birth
• Health
• Growth Development
• Previous laboratory and X-ray studies
• Physical examination
• Anatomic regions
• Organ systems
• Measurements
• Photographs

• Laboratory tests
• X-ray studies
• Other
• Family investigations
• Watchful waiting
• Synthesis
• Pivotal findings
• Pattern recognition
• Comparison with known cases
• Personal experience
• Literature
• Confirmation
• Laboratory
• Clinical course
• Birth of affected relatives
• Intervention
• Treatment
• Counseling
• Follow-up

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