Nelson 648.10: Arthrogryposis — Prenatal Ultrasound Algorithm & Clinical Classification

Fig 648.18 — Proposed Ultrasound Algorithm for Improving the Detection of AMC in Prenatal Care

📐 Prenatal Screening Strategy

Screening for limb, joint, hand, foot, digit anomalies, and fetal movement quality should begin in the first trimester and continue throughout pregnancy. Reduced differentiation into specific movement patterns is often appreciated in the second trimester. Chromosomal microarray analysis is indicated in all fetuses with AMC; further molecular testing (panel and genome-wide sequencing) should be offered based on clinical presentation.

Source: Fleges I, Tercanli S, Hall JG. Fetal arthrogryposis: challenges and perspectives for prenatal detection and management. Am J Med Genet. 2019;181C:327-336. Fig. 2.

Algorithm Flow

📅 First Trimester (11-14 weeks): Screen for limb, joint, hand, foot, digit anomalies. Assess quality of fetal movements (reduced differentiation into specific patterns).

📅 Second Trimester: Monitor for persistent contractures, abnormal joint positioning, reduced fetal movements. Perform detailed fetal anatomy survey.

🔍 If AMC suspected:

Assess for associated anomalies (CNS, cardiac, renal, pulmonary hypoplasia)
Evaluate amniotic fluid volume (polyhydramnios common)
Rule out uterine anomalies, amniotic bands, multiple gestation

🧬 Genetic Testing (all fetuses with AMC):

Chromosomal microarray analysis (CMA)
If negative, consider next-generation sequencing (targeted gene panels, whole exome/genome sequencing) based on phenotype
Specific testing for myotonic dystrophy (DM1) in mother

👩 Maternal Evaluation: Examine for myotonic dystrophy (grip myotonia, percussion myotonia), myasthenia gravis (fatigable weakness, ptosis).

📋 Pregnancy Management: Multidisciplinary planning (neonatology, orthopedics, genetics). Consider in utero stimulation, timing of delivery based on lung maturation.

Fig 648.18: Algorithm for prenatal detection of AMC. Screening starts in first trimester. CMA indicated in all fetuses with AMC. Further molecular testing based on clinical presentation.

Fig 648.13 — Clinical Classification of Arthrogryposis Multiplex Congenita (AMC)

📊 Classification Scheme (Grenoble Alpes University Hospital)

Clinical classification distinguishes AMC into three main groups: Group 1 (Amyoplasia), Group 2 (Distal Arthrogryposis), and Group 3 (with or without CNS involvement, with nine etiologic subgroups).

Source: Le Tanno P, Latypova X, Rendu J, et al. Diagnostic workup in children with arthrogryposis: description of practices from a single reference centre. J Med Genet. 2023;60:13-24. Fig. 2.

Clinical Classification of AMC

📌 Group 1

Amyoplasia (classical arthrogryposis)

Symmetric limb contractures, muscle replaced by fibrous/fatty tissue, sporadic, no CNS involvement.

📌 Group 2

Distal Arthrogryposis (DA)

Hands/feet contractures, proximal joints spared, often AD inheritance (MYH3, TPM2, TNNT3).

📌 Group 3

Other / Syndromic AMC

With or without CNS involvement. Nine etiologic subgroups.

🔍 Group 3 — Etiologic Subgroups (with CNS involvement examples)

SMA (5q) SMALED PCH type 1 CMD (Fukuyama, Walker-Warburg, MEB) LGMD COFS syndrome PWS (Prader-Willi) SLO (Smith-Lemli-Opitz) ARC syndrome OPD syndrome OFD syndrome CDP (chondrodysplasia) CCA (contractural arachnodactyly) CBD (congenital bone disorder)

🧬 Genes / Syndromes in Group 3 (selected)

ARC: Arthrogryposis, renal dysfunction, cholestasis
ARX: Alpha-thalassemia/mental retardation syndrome
CMD: Congenital muscular dystrophies (LAMA2, COL6, FKRP, FKTN, POMT1, POMGnT1, etc.)
COFS: Cerebro-facio-oculo-skeletal syndrome
MEB: Muscle-eye-brain disease
PCH: Pontocerebellar hypoplasia type 1 (EXOSC3, VRK1, TSEN54)
SMA: Spinal muscular atrophy (SMN1), SMALED, SMA with respiratory distress (SMARD1)
SLO: Smith-Lemli-Opitz syndrome
WWS: Walker-Warburg syndrome

Fig 648.13: Clinical classification of AMC distinguishing amyoplasia (Group 1), distal arthrogryposis (Group 2), and syndromic forms with or without CNS involvement (Group 3).