Dysmorphology

FITSUM D. MD
 Dysmorphology

• Studies abnormalities of human form and the

mechanisms that cause them.
• 2.5% of newborns have a recognizable
malformation(s) at birth – single or multiple.

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 Dysmorphology:
Classification of Birth Defects
• Congenital birth defects either
– are isolated, single defects or
– manifest as multiple anomalies.
• Single primary defects can be classified according
to the nature of the presumed cause as
– Malformation,
– Dysplasia,
– Deformation, or
– Disruption.
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 Dysmorphology:
Classification of Birth
Defects
• Malformations and dysplasias affect intrinsic
structure.
• Malformation is a primary structural defect
arising from a localized error in morphogenesis 
abnormal formation of a tissue or organ.
• Dysplasia refers to an abnormal organization of
cells into tissues.
• The distinction of a between the two may be
helpful, but there is much overlap.
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 Dysmorphology:
Classification of Birth Defects
• Deformations and disruptions are secondary
effects that result from forces generated extrinsic
to the affected tissue or organ.
• Deformation is an alteration in shape or
structure of a structure or organ that has
differentiated normally.
• Disruption is a structural defect resulting from
the destruction of a structure that had formed
normally before the insult.
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 Dysmorphology:
Classification of Birth Defects
• More than half of inherited human disorders with
altered morphogenesis display multiple
malformations.
• When several malformations occur in a single
individual, they are classified as
– Syndromes,
– Sequences, or
– Associations.

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 Dysmorphology:
Classification of Birth Defects
• Syndrome is a pattern of multiple abnormalities
that are related by pathophysiology and result
from a common, defined etiology.
• Sequences pattern of multiple anomalies that
occurs when a single primary defect (can have
many etiologies) in early morphogenesis
produces multiple abnormalities through a
cascading process of secondary and tertiary
errors in morphogenesis.
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 Dysmorphology:
Classification of Birth Defects
• Association - nonrandom collection of
malformations in which there is an unclear
relationship among the malformations such that
they do not fit the criteria for a syndrome or
sequence.

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Malformations and/or Dysplasias

• Caused by the combined effects of genes and

environmental factors .
• Some malformations are caused by single gene
defects or abnormalities of multiple genes acting
in concert, and the environment causes others.
• The causes or even the diagnosis is unknown for
40-50% of birth defects.

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Causes of congenital malformations
• Monogenic
• Chromosomal
• Maternal infections
• Maternal illnesses
• Uterine environment
• Medications
• Environmental agents
• Sporadic syndrome complexes e.g CHARGE
• Nutritional e.g NTDs
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 Deformations

• Most deformations involve the musculoskeletal

system /MSS/.
• Fetal movement is required for the proper
development of the normal MSS.
• Anything that restricts fetal movement can cause a
musculoskeletal deformation from intrauterine
molding.
• can be caused by problems either intrinsic or
extrinsic to the developing fetus.
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 Deformations
Two major intrinsic causes of deformations
• primary neuromuscular disorders and
• Oligohydramnios caused by renal defect.
The major extrinsic causes of deformation are
• fetal crowding  restrict fetal movement
e.g. oligohydramnios from chronic leakage of
amniotic fluid,
• breech presentation, and
• abnormal shape of the amniotic cavity.
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 Deformations

• Most children with deformations from extrinsic

causes are otherwise completely normal, and their
prognosis is usually excellent.
• Deformations caused by intrinsic factors, such as
multiple joint contractures resulting from central
nervous system defects, would have a different
prognosis and a far greater significance for the
child.

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 Disruption

• Defects caused by destruction of a previously normally

formed part.
• At least two basic mechanisms  disruption.
1. entanglement followed by tearing apart or
amputation of a normally developed structure by
strands of amnion floating within amniotic fluid
(amniotic bands).
2. interruption of the blood supply to a developing part
 infarction, necrosis, and/or resorption of
structures distal to the insult.

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 Disruption

• Genetic factors usually play a minor role in the

pathogenesis of disruptions;
• Most are sporadic events in otherwise normal
families.
• The prognosis for a disruptive defect is
determined entirely by the extent and location of
the tissue loss.

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Multiple Anomalies Syndrome and
Sequence

• When evaluating a child with multiple anomalies,

one must differentiate a sequence from a multiple
malformation syndrome.
• In the former, recurrence risk counseling for the
multiple anomalies depends entirely on the risk of
recurrence for the single localized malformation.
– e.g. The Robin malformation sequence

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Multiple Anomalies Syndrome and
Sequence

• The Robin malformation sequence is a pattern of

multiple anomalies produced by mandibular
hypoplasia of different causes. Because the
tongue is relatively large for the oral cavity, it
drops back (glossoptosis), blocks closure of the
posterior palatal shelves, and causes a U-shaped
cleft palate.

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Approach to the Dysmorphic Child

History
• Elements that are related to etiologic factors.
– pedigree or family history that is necessary to assess the
inheritance pattern.
• The perinatal history
– recurrent miscarriages that may be a sign of a familial
chromosomal disorder,
– factors that may relate to deformations or disruptions
(oligohydramnios), and
– Maternal exposures to teratogenic drugs or chemicals
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Approach to the Dysmorphic Child

History
• Natural history of the phenotype.
– Malformation syndromes caused by chromosomal
aneuploidy or aneusomy and single gene pleiotropic
disorders are usually static.
– In contrast, disorders that cause dysmorphic features
by the mechanism of metabolic perturbations are either
mild or inapparent at birth and progress relentlessly,
causing deterioration of the patient over time.

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Approach to the Dysmorphic Child

Physical examination
• Organized and systematic cataloguing of the size
and structure of various body structures.
• Categorize abnormalities as “major” or “minor”.
• Major defects are those either
– Cause dysfunction (absence of a digit) OR
– Require surgical correction (polydactyly), and
• Minor defects neither cause significant
dysfunction nor require surgical correction.
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Approach to the Dysmorphic Child

Laboratory & imaging studies: individualized

• Renal ultrasound
• Echocardiography
• Full skeletal survey
• Brain CT/ MRI

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Approach to the Dysmorphic Child

Clinical indications for karyotype analysis

• At least one major and two minor malformations.
• At least two major malformations.
• Developmental OR growth retardation with two or
more major or minor anomalies.

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Approach to the Dysmorphic Child

Management and Counseling : individualized

• e.g Children with
– Down syndrome have a high incidence of
hypothyroidism
– achondroplasia have a high incidence of cervico-
medullary junction constriction.
• early and accurate diagnosis,  anticipatory
guidance and medical monitoring of patients for
syndrome-specific medical risks can prolong and
improve their quality of life.
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Approach to the Dysmorphic Child

Management and Counseling :

• accurate diagnosis also provides data for
appropriate recurrence risk estimates.
• Genetic disorders may have direct effects on only
one member of the family, but the diagnosis of the
condition has implications for the entire family.
• One or both parents may be carriers; siblings may
be carriers or may wish to know their at-risk status
when they reach their reproductive years.
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THANK YOU!!!

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