Inheritance Patterns of Orthopaedic Syndromes

Author: Derek Moore

Topic updated on 03/21/13 7:32pm

Autosomal Dominant
Allows for specific patterns of inheritance controlled by a single gene pair (“monogenic”) 4 different types of patterns autosomal dominant autosomal recessive x-linked dominant x-linked recessive
Autosomal Dominant

Description only need to get the abnormal gene from one parent in order for you to inherit the disease. Examples Syndactyly polydactyly Marfan's (fibrillin) Cleidocranial Dysostosis Hereditary multiple exostosis (HME) Achondroplasia (FGFR3) MED (COMP gene - Type II collagen) Metaphyseal chondrodysplasia (Schmid and Jansen types) Kniest dysplasia Malignant hyperthermia Ehlers-Danlos syndrome Osteogenesis imperfecta (types I and IV) Osteochondromatosis Osteopetrosis (tarda, mild form
Autosomal Recessive

Description an autosomal recessive disorder means two copies of an abnormal gene must be present in order for the disease or trait to develop. Examples Diastrophic Dysplasia (sulfate transporter gene) Friedreich's Ataxia (frataxin) Gaucher disease SMA (survival motor neuron gene) Sickle cell anemia Osteogenesis imperfecta (II and III) Hypophosphatasia Osteopetrosis (infantile, malignant form)
Sex-linked Recessive (males only)


Description X-linked diseases usually occur in males. Males have only one X chromosome. A single recessive gene on that X chromosome will cause the disease. Examples Duchenne Mus. Dyst. (absent dystrophin) Becker's Mus. Dyst. (defective dystrophin) Hunter's Hemophilia SED tarda
Sex-linked Dominant

Examples Hypophosphatemic rickets Leri-Weill dyschondrosteosis (bilateral Madelung's deformity)
Multiple inheritance patterns
Examples CMT (AD, AR, Xlink)(myelin protein 22) Osteopetrosis (AD, AR) Osteogenesis Imperfecta (AR, AD) Neurofibromatosis (AD, AR)(neurofibromin protein) SED (AD, Xlink)(COL2A1, Type II collagen)
Miscellaneous Genetic Inheritance
Imprinting a genetic phenomenon by which certain genes are expressed in a parent-of-origin-specific manner Examples Angelman Syndrome Prader-Willi Syndrome Anticipation a phenotype occurs earlier (and typically worse) in each subsequent generation common in trinucleotide repeat disorders

Please Rate Educational Value!

3.0

Average 3.0 of 6 Ratings

Qbank (5 Questions)

TAG

(OBQ11.272) A 46-year-old female begins to have personality changes, cognitive decline, and chorea. Her father began having similar but less severe symptoms at age 55 before passing away 6 years later. One of her 2 older siblings has also begun to show deterioration. Which of the following describes the hereditary pattern of this disease? Topic

Review Topic

1. Autosomal dominant with variable penetrance
2. Autosomal recessive with variable penetrance
3. X-linked recessive
4. Autosomal dominant with anticipation
5. Autosomal dominant with imprinting

PREFERRED RESPONSE ▶

DISCUSSION: This clinical vignette describes a patient with Huntington's disease. Huntington's disease has an autosomal dominant hereditary pattern with anticipation. Anticipation is a term used to describe trinucleotide repeat disorders that if passed on, will present earlier and more severely in affected subjects than their than affected parent. In Huntington's disease, it is due to a "CAG" trinucleotide repeat on chromosome 4. Subjects with an affected parent have a 50% chance of inheriting the disease from them, and if present will have more severe disease.

Deighton et al provide a review on the genetics of musculoskeletal disease including the hereditary pattern of anticipation.

REFERENCES:

1. Deighton CM, Thomson G. Genetic anticipation and musculoskeletal disease. Ann Rheum Dis. 1994 Dec;53(12):787-8 PMID:7864684 (Link to Abstract)

2. Cole WG. Genetic aspects of orthopaedic conditions. In: Morrissy RT, Weinstein SL, eds. Lovell and Winter's Pediatric Orthopaedics. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:145-165.

Question Authors:

David Abbasi MD, Ben Taylor MD, Michael Hughes MD,

Please Rate Educational Value!

2.0

Average 2.0 of 10 Ratings

TAG

(OBQ07.219) Which of the following conditions exhibit the inheritance pattern shown in Figure A, assuming no new mutations? Topic

Review Topic

FIGURES: A

1. Duchenne muscular dystrophy
2. Hunter's syndrome
3. Hemophilia
4. Spondyloepiphyseal dysplasia (SED) tarda
5. Diastrophic dysplasia

PREFERRED RESPONSE ▶

DISCUSSION: The pedigree chart (males are squares and females are circles) shown in Figure A demonstrates an autosomal recessive trait. Diastrophic dysplasia is the only autosomal recessive condition with all of the other options being X-linked recessive disorders. Along with Becker's MD these are the main orthopaedic X-linked recessive disorders. There are many more autosomal recessive orthopaedic disorders. Autosomal recessive pedigrees often appear in both sexes with equal frequency, tend to skip generations, and affected offspring are usually born to unaffected parents. When both parents are hetrozygote, approximately 1/4 of the progeny will be affected. X-linked and autosomal dominant disorders will not skip generations. X-linked recessive disorders will always have affected sons if the mother has the disease (this does not occur in the 3rd cross of Figure A on the far right).

REFERENCES:

1. Brinker MR: Callular and molecular biology, immunology, and genetics in orthopaedics, in Miller MD (ed): Review of Orthopaedics, ed 3. Philadelphia, PA, WB Saunders, 2000, pp81-94

Question Authors:

Michael Hughes MD, Patrick McCulloch MD,

Please Rate Educational Value!

3.0

Average 3.0 of 15 Ratings

TAG

(OBQ06.228) Prader-Willi syndrome and Angelman syndrome are examples of a genetic phenomenon by which certain genes are expressed in a parent-of-origin-specific manner. What is the name of this genetic phenomenon? Topic

Review Topic

1. Sex-linked dominant transmission
2. Y-linked dominant transmission
3. X-linked dominant transmission
4. Genomic imprinting
5. Mendelian inheritance

PREFERRED RESPONSE ▶

DISCUSSION: Definition of genetic imprinting: the allele that is expressed is determined solely on which parent contributes it. In Angelman syndrome the defective gene comes from the mother, leading to epilepsy, tremors, and smiling facies. In Prader-Willi syndrome the defective gene comes from the father resulting in hypotonia, obesity, hypogonadism. These are classic examples of genetic imprinting in humans. Usually, diseases resulting from defective structural proteins are autosomal dominant, while defective enzymes are autosomal recessive.

REFERENCES:

1. Vogels A, Fryns JP. The Prader-Willi syndrome and the Angelman syndrome. GenetCouns. 2002;13(4):385-96. Review PMID:12558108 (Link to Abstract)

2. Driscoll DJ. Genomic imprinting in humans. Mol Genet Med. 1994;4:37-77.Review PMID:7981630 (Link to Abstract)

Question Authors:

Dan Prince MD, Derek Moore,

Please Rate Educational Value!

2.0

Average 2.0 of 9 Ratings

TAG

(OBQ05.228) Which of the following is a phenomenon whereby the symptoms of a genetic disorder become apparent at an earlier age as it is passed on to the next generation? Topic

Review Topic

1. Genetic drift
2. Expansion
3. Mendelian inheritance
4. Anticipation
5. Phenotypic plasticity

PREFERRED RESPONSE ▶

DISCUSSION: Anticipation is a phenomenon whereby the symptoms of a genetic disorder become apparent at an earlier age as it is passed on to the next generation. In most cases, an increase of severity of symptoms is also noted. Anticipation is common in trinucleotide repeat disorders such as Huntington's disease, myotonic dystrophy, Friedreich ataxia, and Fragile X syndrome. Illustration A shows the genetics of the trinucleotide repeat disorders.

Illustrations: A

REFERENCES:

Question Authors:

Ben Taylor MD, Patrick McCulloch MD, Michael Hughes MD,

Please Rate Educational Value!

2.0

Average 2.0 of 13 Ratings

Videos

Chorea from genetic disorder

Basic Science - Physical Exam - Inheritance Patterns of Orthopaedic Syndromes

Clinical video showing patient with chorea from genetic disorder.

2/1/2012

37 views

See More Videos

Evidence & References Show References

Textbooks

Review of Orthopaedics, 6th Edition, Mark D. Miller MD, Stephen R. Thompson MBBS MEd FRCSC, Jennifer Hart MPAS PA-C ATC, an imprint of Elsevier, Philadelphia, Copyright 2012
AAOS Comprehensive Orthopaedic Review, Jay R. Leiberman. Published by American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2009
Orthopaedic Knowledge Update 10, John M Flyn. Published by American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2011
Hoppenfeld SP. Surgical Exposures in Orthopaedics: The Anatomic Approach. Lipponcott, Williams, and Wilkins, Philadelphia, PA, Copyright 2009
Orthopaedic In-training Examination (OITE) Questions 2004-2012, American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2004-2012
Self-Assessment Examination (SAE) Questions 2004-2012, American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2004-2012
Zuscik MJ, Drissi MH, Chen D, Rosier RN. Molecular and cell biology in orthopaedics. In: Einhorn TA, O'Keefe RJ, Buckwalter JA, eds. Orthopaedic Basic Science: Foundations of Clinical Practice. 3rd ed. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2007:3-23.
Cole WG. Genetic aspects of orthopaedic conditions. In: Morrissy RT, Weinstein SL, eds. Lovell and Winter's Pediatric Orthopaedics. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:145-165.
Brinker MR: Callular and molecular biology, immunology, and genetics in orthopaedics, in Miller MD (ed): Review of Orthopaedics, ed 3. Philadelphia, PA, WB Saunders, 2000, pp81-94

Undefined

Deighton CM, Thomson G. Genetic anticipation and musculoskeletal disease. Ann Rheum Dis. 1994 Dec;53(12):787-8 PMID:7864684 (Link to Abstract)
Cole WG. Genetic aspects of orthopaedic conditions. In: Morrissy RT, Weinstein SL, eds. Lovell and Winter's Pediatric Orthopaedics. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:145-165.
Vogels A, Fryns JP. The Prader-Willi syndrome and the Angelman syndrome. GenetCouns. 2002;13(4):385-96. Review PMID:12558108 (Link to Abstract)
Driscoll DJ. Genomic imprinting in humans. Mol Genet Med. 1994;4:37-77.Review PMID:7981630 (Link to Abstract)

Topic Comments

Subscribe status: On Off

Recent on Bottom | Recent on Top

Page:1

Inheritance Patterns of Orthopaedic Syndromes

Qbank (5 Questions)

Question Comments

Question Comments

Question Comments

Question Comments

Videos

Evidence & References Show References

Topic Comments