Is Arthrogryposis hereditary?

TL;DR: Arthrogryposis, or Arthrogryposis Multiplex Congenita (AMC), is a clinical finding rather than a single disease, and while it is often genetic, it is not always hereditary. Whether it is inherited depends entirely on the specific underlying syndrome causing the joint contractures, which can range from spontaneous de novo mutations to clear autosomal dominant or recessive inheritance patterns.

Is Arthrogryposis considered a hereditary condition?

In clinical genetics, it is essential to distinguish between "genetic" and "hereditary." Arthrogryposis is almost always genetic, meaning it results from alterations in an individual's DNA or fetal development, but it is not always hereditary, meaning it is not always passed down from parents. Many cases of Arthrogryposis occur sporadically due to de novo mutations—genetic changes that happen for the first time in an individual and are not present in the parents. Other cases are caused by environmental factors affecting fetal movement, such as uterine crowding or maternal illness, which are not hereditary at all.

What are the inheritance patterns of Arthrogryposis?

Because Arthrogryposis is an umbrella term for over 400 different conditions, the inheritance pattern depends on the specific diagnosis. Some forms are inherited in an autosomal dominant manner (50% risk to offspring), while others are autosomal recessive (25% risk if both parents are carriers), or X-linked. Because there are so many subtypes, you cannot assume a specific risk percentage without a precise molecular diagnosis. The 383 members of the DiseaseMaps community living with Arthrogryposis represent a diverse group, highlighting the importance of individual genetic evaluation to determine if a specific form of Arthrogryposis has a risk of recurrence in future pregnancies.

How does genetic testing help families?

Genetic testing is the gold standard for understanding the cause of Arthrogryposis and determining its recurrence risk. We typically recommend the following diagnostic steps for families:

• Clinical Exome Sequencing (CES) or Panel Testing: These tests analyze hundreds of genes associated with muscle, nerve, and connective tissue disorders to identify the specific mutation.


• Chromosomal Microarray (CMA): Used to identify large deletions or duplications in the genetic code that might cause the condition.


• Parental Testing: If a pathogenic variant is identified in a child, parents should be tested to see if they are carriers or if the mutation is de novo.


• Genetic Counseling: This is vital for interpreting test results, discussing family planning, and understanding the implications for siblings and other relatives.

What should families know about recurrence and prenatal diagnosis?

If a specific genetic cause for Arthrogryposis is identified, recurrence risk can be calculated with high accuracy. For families with a known autosomal recessive mutation, there is a 25% chance for each pregnancy to be affected. If the condition is caused by a de novo mutation, the recurrence risk for future siblings is generally low (typically less than 1%), though germline mosaicism remains a rare possibility. Prenatal diagnosis options, such as amniocentesis or chorionic villus sampling (CVS), are available for families who have already identified the causative mutation in a previous child or parent.

Next steps

• Consult with a clinical geneticist to review your family history and determine if genetic testing is appropriate.


• Request a referral to a pediatric neurologist or orthopedist to manage the muscular and skeletal symptoms associated with Arthrogryposis.


• Join the DiseaseMaps.org community to connect with other families and share experiences regarding diagnosis and management.


• Speak with a genetic counselor before planning a pregnancy to understand your specific recurrence risks based on your genetic test results.

Medical disclaimer: This information is for educational purposes only and does not constitute medical advice, diagnosis, or treatment; always seek the advice of your physician or other qualified health provider with any questions regarding a medical condition.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Arthrogryposis multiplex congenita.


• Orphanet: Rare disease database for Arthrogryposis.


• OMIM (Online Mendelian Inheritance in Man): Database of genes and genetic disorders.


• Arthrogryposis Multiplex Congenita Support, Inc.