Arthrogryposis

A newborn with multiple congenital joint contractures present at birth, affecting two or more body areas. Arthrogryposis multiplex congenita (AMC) is a descriptive label, not a diagnosis: it describes a final common phenotype produced by anything that reduces fetal movement in utero. The bedside task is to localize the cause along the motor unit (or beyond it to connective tissue or extrinsic constraint), examine the mother, and recognize that two thirds of AMC cases are amyoplasia, a sporadic non-syndromic entity with characteristic posture.

Decreased fetal movement, from any cause, produces contractures. The differential is therefore a localization exercise:

1. Neurogenic: anterior horn cell or peripheral nerve hypoplasia (SMA, SMARD1, brain malformation, cervical spine).
2. Myogenic: congenital muscular dystrophies, congenital myopathies, congenital myotonic dystrophy.
3. Connective tissue: distal arthrogryposis syndromes, connective tissue disorders.
4. Extrinsic constraint: oligohydramnios, uterine anomaly, twin gestation.
5. Mixed / unknown: amyoplasia is the largest single category.

Examine the mother. Myotonic dystrophy is the classic "examine mom" diagnosis: a mildly affected mother may have grip myotonia, frontal balding, ptosis, and a long face, with an infant who has severe congenital myotonic dystrophy with arthrogryposis and respiratory failure.

Amyoplasia (sporadic, the majority)

About two thirds of AMC. Symmetric, internally rotated shoulders, extended elbows, pronated forearms, flexed wrists, hands in a thumb-in-palm position, fingers flexed; lower limbs often in equinovarus. Trunk and face are spared. Cognition usually normal. Sporadic, very low recurrence risk. Etiology likely vascular disruption to developing motor units in early gestation.

Distal arthrogryposis syndromes

Autosomal dominant; hands and feet predominantly affected with relatively spared proximal joints and normal cognition.

• Distal arthrogryposis type 1 (TPM2, MYBPC1, TNNI2): camptodactyly + ulnar deviation + calcaneovalgus or equinovarus feet.
• Distal arthrogryposis type 2A (Freeman-Sheldon "whistling face" syndrome) (MYH3, AD): hands + feet contractures + characteristic small puckered mouth + H-shaped chin dimple + deep-set eyes. (No condition leaf to link.)
• Distal arthrogryposis type 2B (Sheldon-Hall syndrome) (MYH3, TNNI2, TNNT3, TPM2): distal contractures + downslanting palpebral fissures + small mouth, less severe than Freeman-Sheldon. (No condition leaf to link.)

Fetal akinesia spectrum

• Fetal akinesia deformation sequence (FADS) / Pena-Shokeir phenotype: severe arthrogryposis + pulmonary hypoplasia + craniofacial anomalies (depressed nasal tip, low-set ears) + IUGR + polyhydramnios. Lethal in the neonatal period. Many genetic causes converging on the neuromuscular junction (RAPSN, DOK7, CHRNA1, MUSK) or muscle. (No condition leaf to link.)
• Multiple pterygium syndrome (Escobar) (CHRNG, AR): webs (pterygia) across multiple joints (neck, axilla, antecubital, popliteal) + contractures + downslanting palpebral fissures. Lethal forms exist. (No condition leaf to link.)

Anterior horn cell

• Spinal muscular atrophy with respiratory distress 1 (SMARD1) (IGHMBP2, AR): early respiratory failure (diaphragmatic) + distal weakness. A specific severe phenotype distinct from typical SMA. (Linking to the main SMA leaf.)
• Classic SMA type 1 usually presents after birth without arthrogryposis, but rare in utero severe forms can.

Muscle

• Congenital muscular dystrophy (LAMA2 merosin-deficient, alpha-dystroglycanopathies): contractures + early weakness + elevated CK + brain and eye involvement in some (Walker-Warburg, muscle-eye-brain).
• Congenital myopathies (nemaline, central core): hypotonia + weakness; biopsy-defined.
• Congenital myotonic dystrophy (DMPK, maternal inheritance with anticipation): polyhydramnios history + talipes equinovarus + arthrogryposis + tented upper lip + severe weakness. Examine the mother for grip myotonia.

Extrinsic / constraint

• Oligohydramnios sequence (Potter): bilateral renal agenesis or severe dysplasia produces oligohydramnios, fetal compression, contractures, pulmonary hypoplasia, characteristic facies.
• Uterine anomaly, fibroids, twin gestation: mechanical constraint.

The bedside localization narrows what to send first.

1. Detailed neurologic exam: reflexes (preserved or brisk in central, absent in peripheral), antigravity strength, fasciculations (tongue in SMA), cranial nerves.
2. Examine the mother: grip myotonia, ptosis, frontal balding, percussion myotonia. Photographs of mom in childhood are useful.
3. CK: elevated in muscle disease; normal in anterior horn cell, central, and most distal arthrogryposis.
4. EMG / nerve conduction: distinguishes neurogenic from myogenic when bedside is ambiguous.
5. Brain MRI: cerebellar hypoplasia, cortical malformations (alpha-dystroglycanopathy).
6. Renal ultrasound: oligohydramnios sequence work-up.
7. Echocardiogram: cardiomyopathy in some myopathies.
8. Targeted gene testing: SMN1 deletion (SMA), DMPK CTG expansion (congenital myotonic dystrophy; remember triplet repeat methods, not standard sequencing), distal arthrogryposis panel (MYH3, TPM2, TNNI2, TNNT3), congenital muscular dystrophy panel (LAMA2, alpha-dystroglycanopathies), fetal akinesia / pterygium panels.
9. Chromosomal microarray + karyotype for syndromic features.
10. Exome / genome sequencing for unclear cases or after a negative targeted panel.
11. Early physical and occupational therapy: passive ranging in the first weeks improves long-term function; serial casting for foot deformities; orthopedic referral for surgical planning.