What Are the Classification of Genetic Disorders?

Patient Presentation
A pediatrician was telling her partner about a good conversation that she had that day with a parent. She had followed an 8-year old female who had facial hemi-hypertrophy. Over time, several evaluations including consultations with genetics, neurology and imaging. did not reveal a diagnosis. The mother was a strong advocate but wanted to continue to pursue “reasonable” evaluations. The pediatrician would review the medical literature about hemi-hypertrophy and the mother looked at the Internet and found other local services to help support her child and family. During a routine visit, her dentist noticed an unusual lip lesion. The mother agreed to have a picture taken and it was sent to a dental pathologist, who said that it was classic for the diagnosis of Parry-Romberg syndrome which is hemifacial atrophy. (A geneticist later confirmed the diagnosis.) The mother called the pediatrician to let her know the diagnosis and stated that it certainly didn’t change her love of her child, but now she had a diagnosis and she would have a better idea of what the future may hold for her daughter and family. The pediatrician commented that she herself was pleased that the mother felt supported by her efforts to continue to evaluate the child, and that this family made her carefully look at parent desires for testing and to have honest conversations with families about testing and necessity of procedures. She said “…genetics is such a rapidly advancing field that it is always a good thing to have follow-up of your undiagnosed cases.”

Parry-Romberg syndrome is a rare disorder with atrophy of the soft tissues and skin of the face (usually left-sided) called hemifacial atrophy. External tissues are more affected but also eye, oral, and neck structures. Skin hypo- or hyperpigmentation and whitening of the hair and/or alopecia may occur. Trigeminal neuralgia and seizures can also be seen. Onset is usually between 5-15 years and is more common in females. The atrophy usually lasts 2-10 years and then seems to enter a stable phase. There appears to be a genetic basis for this disease but the exact mechanism is unknown. In the classification below, it would be a miscellaneous disorder.

Learning Point
As the tools, techniques and knowledge in the exploding field of genetics continues into the future, many of the disorders and syndromes that are currently classified into one category will necessarily be reclassified because of new knowledge. The field of epigenetics is ripe for expanding classifications and better understanding the natural history of these problems.

Genetic disorder categories include:

  • Chromosomal disorders
    • Whole or part of a chromosome is missing or duplicated. These are large enough to be seen on a standard karyotype.
    • Examples: Trisomy 21, Cri-du-chat, Turner, Kleinfelter
    • Testing: karyotype
  • Microdeletion or microduplication
    • Part of a chromosome is missing or duplicated. These are often too small to be seen on a standard karyotype
    • Examples: DiGeorge syndrome, Prader-Willi syndrome (deletion type), Smith-Magenis syndrome, Williams syndrome
    • Testing: FISH – fluorescent in situ hybridization, aCHG – array comparative hybridization
  • Single gene disorders
    • A mutation on a single gene. May be autosomomal dominant, autosomal recessive, X-linked.
    • Examples: Cystic fibrosis, Duchenne muscular dystrophy, Marfan syndrome, Sickle cell anemia
    • Testing: DNA sequencing, mutation analysis, deletion testing
  • Triplet repeat disorders
    • Exceeding the number of normal trinucleotide repeats in genes. The normal number varies depending on the gene.
    • Examples: Fragile X, Huntington’s disease
    • Testing: DNA testing for number of repeats
  • Epigenetic disorders
    • The genetic sequence is not changed, but the expression of the DNA is altered
    • Examples: Angleman, Beckwith-Wiedemann syndrome, Prader-Willi (methylation or isodisomy type)
    • Testing: Methylation testing
  • Multifactorial disorders
    • Combination of genetics and environment
    • Examples: isolated congenital heart defects, cleft lip and palate, pyloric stenosis
    • Testing: may be available if part of a syndrome, but usually no testing is available
  • Miscellaneous
    • Not otherwise categorized, and also includes:
      • Associations or non-random association of anomies without a known genetic basis, example is CHARGE association
      • Disruptions or morphological defect of a previously normal organ, example is amniotic bands
      • Sequences or one malformation leads to other malformation, example is Pierre-Robin sequence

Questions for Further Discussion
1. What types of disorders can be identified on newborn screening using tandem mass spectrometry?
2. What tests do your state/country perform as part of newborn screening?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com.

Information prescriptions for patients can be found at MedlinePlus for these topics: Facial Injuries and Disorders and Genetic Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

NINDS Parry-Romberg Information Page. National Institute of Neurological Disorders and Stroke.
Available from the Internet at http://www.ninds.nih.gov/disorders/parry_romberg/parry_romberg.htm (rev. 2/2007, cited 10/4/10).

Shur N, Abulo D. Genetic Syndromes: From Clinical Suspicion to Referral to Diagnosis. Pediatric Annals. 2009;38;419-425.

Online Mendelian Inheritance in Man. Hemifacial atrophy, progressive; HFA.
Available from the Internet at http://www.ncbi.nlm.nih.gov/omim (rev. 4/30/2010, cited 10/4/2010).

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    6. Information technology to support patient care decisions and patient education is used.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Interpersonal and Communication Skills
    17. A therapeutic and ethically sound relationship with patients is created and sustained.
    18. Using effective nonverbal, explanatory, questioning, and writing skills, the healthcare professional uses effective listening skills and elicits and provides information.
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Professionalism
    22. Sensitivity and responsiveness to patients’ culture, age, gender, and disabilities are demonstrated.

  • Systems Based Practice
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.


    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

    Stacy McConkey, M.D.
    Associate Professor of Pediatrics, University of Iowa Children’s Hospital