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Author: Laurie Ann Demmer, M.D.
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Dysmorphology and Syndromes


Jorde, Carey, Bamshad & White: Medical Genetics, 3rd edition, C.V. Mosby Publishing, 2005.

  • Chapter 14, 316-321


  1. To understand the underlying causes of birth defects
  2. To know which patients should be referred to a clinical geneticist
  3. To understand what constitutes a genetic evaluation

Clinical Genetics

The diagnosis, counseling and care of individuals and families with inherited, teratogenic, or sporadic conditions.

Reasons to Refer a Patient to Clinical Genetics:

  • Prenatal test(s) showing abnormalities
  • Infant with one or more birth defects, an unusual appearance, or a chromosome abnormality
  • Child or adult with an unusual appearance, mental retardation or history of birth defect(s)
  • Family history of birth defect(s) or inherited conditions
  • Infertility or recurrent miscarriages
  • Abnormal state laboratory newborn screen
  • Early onset cancer/strong family history of cancer

Reasons For Making A Genetic Diagnosis:

  • Defines the gamut of abnormalities present (i.e., what other abnormalities should be expected and what should not be expected)
  • May give a more definite prognosis
  • Can help explain why the condition occurred
  • Allows for counseling of all family members with regards to recurrence risks, need for additional genetic testing


Birth defect

A condition present at birth, which requires medical, surgical or cosmetic intervention. At birth, 3% of children are recognized to have a birth defect and by 1 year of age 4% of children are found to have a birth defect. Ex: congenital heart disease, polydactyly, holoprosencephaly

Dysmorphic Features

Variants of physical features that are present in less than 2-3 % of the general population. Ex: single transverse palmar crease


A pattern of multiple anomalies thought to be pathogenetically related.


Down syndrome, neurofibromatosis type 1


A nonrandom occurrence in two or more individuals of multiple anomalies.

Example 1

VATER association:

Vertebral anomalies

Anus, imperforate

Trachea/Esophageal fistula Renal or

Radial anomalies

Example 2

CHARGE association:

Coloboma (keyhole defect of iris, retina, or optic nerve)

Heart defects

Atresia of the choanae (bony blockage of nasal passage)

Retarded growth &/or development

Genital hypoplasia (small penis and undescended testes)

Ear anomalies (both structure and hearing loss)


A pattern of multiple anomalies derived from a single known or presumed prior anomaly or mechanical factor.

Example 1

Pierre-Robin sequence:

In utero, the chin is very small and the tongue prevents closure of the soft palate (cleft palate). After birth, the small chin results in the tongue falling back and obstructing the airway.

Example 2

Potter sequence:

In utero, lack of fetal urination (secondary to absent or non-functional kidneys or blockage of urine outlet, etc) leads to anhydramnios (absence of amniotic fluid), which leads to fetal compression and pulmonary hypoplasia resulting in neonatal death.

Birth Defects

Pathogenetic Basis of Birth Defects

  1. Malformation: A morphologic defect of an organ, part of an organ, or a larger region of the body resulting from an intrinsically abnormal development process. Ex: cleft lip, syndactyly (fusion of one or more digits)
  2. Deformation: An abnormal form or position of a part of the body caused by non-disruptive mechanical forces. Ex: congenital hip dysplasia due to prolonged breech position
  3. Disruption: A morphologic defect resulting from a breakdown of, or interference with, an originally normal developmental process. Ex: amniotic band syndrome resulting in amputation of a finger
  4. Dysplasia:Abnormal cellular organization or function within a specific tissue type throughout the body, resulting in clinically apparent structural changes. Ex: osteogenesis imperfecta (OI) which is due to a defect in collagen production

Understanding the underlying bases of birth defects is critical since it often can help determine if there is a recurrence risk for that particular birth defect.

Causes of Birth Defects

  1. Chromosome abnormalities
  2. Single gene defects (Mendelian disorders)
  3. Imprinting
  4. Multifactorial
  5. Sporadic/field defects
  6. Prenatal teratogen exposure
  7. Mitochondrial defects


Substances which when a pregnant woman is exposed to them can lead to birth defects in her fetus.

  • Infections: rubella, syphilis, CMV, etc.
  • Medications: thalidomide, accutane, anti-epileptics such as Tegretol and Dilantin.
  • Drugs of abuse: alcohol, cigarettes, cocaine, etc.
  • External agents: radiation, hyperthermia (increased risk for spinal bifida).

The effect of a teratogen is dependent on gestational time of exposure, dose and the genetic background of the mother and fetus. For example, fraternal twins have been reported who were exposed to large amounts of alcohol in utero. One twin had classic fetal alcohol syndrome and the other did not.

Steps in Diagnostic Evaluation

Pregnancy History

  • Maternal age: 35 years or older at time of delivery increases risk for an infant with a chromosomal anomaly such as Down syndrome.
  • Maternal illnesses: diabetes mellitus especially if poorly controlled increases risk for a variety of birth defects.
  • Maternal exposures: see teratogens above

Birth History

  • Mode of delivery (vaginal, C-section) and fetal presentation (breech, etc)
  • Difficult delivery/poor Apgar scores? (may increase risk of asphyxia, cerebral palsy).
  • Was resuscitation required?
  • Placenta abnormalities (small or infarcted placenta may be associated with poor fetal growth).
  • Medical History of Child
  • Frequent infections?
  • Surgical problems?
  • Hospitalizations?
  • Developmental History
  • Timing of early developmental landmarks (gross and fine motor skills as well as language development)
  • School problems (repeating grades, etc)
  • Behavior problems (autism, attention deficit hyperactivity disorder)
  • Learning difficulties
  • Family History
  • Other individuals with birth defects
  • Recurrent miscarriages
  • Mental retardation or learning problems
  • Known genetic disorder
  • Physical Examination (detailed look at the whole body)
  • Skin – birth marks, discoloration, stretch marks
  • Size – height, weight and head circumference, compared to normal standards
  • Face – look for unusual features or distinctive pattern
  • Neck – increased skin or webbing
  • Chest – pectus excavatum or carinatum
  • Heart – murmur or click may indicate congenital heart defect
  • Abdomen – umbilical hernia or omphalocele
  • Genitalia – micropenis, undescended testes, ambiguous genitalia
  • Extremities – range of motion of joints, dermatoglyphics
  • Neurologic – increased or decreased muscle tone i.e. hypertonia or hypotonia