1. Cheryl Longman Consultant Clinical Geneticist
Arthrogryposis
Cheryl Longman
Consultant Clinical Geneticist

2. Arthrogryposis ARTHRON - joint GRYPOSIS - curvature
MULTIPLEX - multiple
CONGENITA - born with it
…affecting two or more different joints
…symmetrical and non-progressive

3. Arthrogryposis 1 in 3-5,000 live births Male = female
Not a single condition: end result of fetal akinesia
>400 conditions
>150 genes

4. Non-specific features
Fusiform limbs
Absent/reduced creases
Dimpling
Craniofacial: micrognathia, cleft palate, hypertelorism
Osteoporosis and fractures
Early onset merges with lethal contracture syndromes
Pterygia
IUGR
Pulmonary hypoplasia

5. Diagnosis matters because it informs
Risk to sibs (0-100%), offspring, wider family
Risk of complications
Respiratory failure
Malignant hyperthermia
Cardiomyopathy
Treatment
Occasionally specific treatments
Management of contractures

6. An Approach To Diagnosis
Amyoplasia
Maternal factors
Connective tissue/skeletal
Central
Peripheral neuromuscular
Nerve
NMJ
Muscle: distal arthrogryposis & congenital myopathies

7. Amyoplasia One third of arthrogryposis Presumed vascular
Typical arm posture
Forehead haemangioma
Gastroschisis 10%

8. Amyoplasia: Management
Orthopaedic-led
WoS MDT clinic
Treat as soon after birth as possible
Aim to allow milestones at the right time
Judicious surgery
"Lifetime" orthoses

9. Maternal Factors Illness eg Myasthenia, MS, infection, trauma …..
Hyperthermia
Drugs eg cocaine, alcohol excess
Uterine constraint

10. 8.9M livebirths , fetal deaths from 20 wk and TOPs coded AMC over 26y
757 cases ~ 1 in 11,000
Maternal details for a third: vast majority no illnesses or drug use
2300 cases over 35 yrs
33 with uterine structural anomalies
29 had a specific recognisable form of arthrogryposis
2 where constraint likely cause- craniofacial asymmetry & early resolution
> Caution in ascribing arthrogryposis to maternal factors

11. Central Clues Dysmorphic/multisystem features Cognitive involvement
Spasticity/seizures
Abnormal brain imaging
Genetic testing
Array CGH
Single gene test vs ID panels
ZC4H2

12. Nerve: SMA and motor neuronopathies
Clues: Distal weakness and wasting, neurophysiology, brain MRI
Phenotypic spectrum of some genes can extend to severe prenatal contractures with pterygia
Some carry respiratory risk
Genetic testing
SMA panel covers dHMNs
BICD2

13. Neuromuscular junction
Genes encode NMJ components
Same genes cause “lethal pterygium syndromes”
Clues: fatiguable weakness, fluctuations, ptosis, opthalmoplegia, apnoeas
Neurophysiology
Specific medication
RAPSN

14. Distal Arthrogryposes
Common inherited cause, often dominant
Characteristic patterns
Overlap with congenital myopathies
Genetic testing via arthrogryposis panel
TNNT3

15. Congenital Myopathies
Phenotypic spectrum can be wide
Wide intra-familial variability
Caution in predicting prognosis early- treat the person not the gene
Associated risks in some
Respiratory weakness
Malignant hyperthermia

16. Conclusions Arthrogryposis is a description Diagnosis informs
Recurrence risk
Risk of associated complications eg respiratory weakness
Management
Phenotypic spectrum of many genes ranges from lethal contracture syndromes > arthrogryposis > milder phenotypes
Advances in genetic testing are improving the ability to make timely genetic diagnoses

17. Thanks for listening