IllnessArthrogryposis, distal; differential diagnosis

After exclusion of neuromuscular and amyoplasic causes as well as syndromes

NGS +

[Sanger]

Distal arthrogryposis is characterized by contractures that limit movement of the hands and feet, with camptodactyly, overlapping fingers and ulnar deviation; clubfoot is also common. The specific hand and foot abnormalities vary among affected individuals. Contractures may be due to prenatal problems with pysiological muscle contractions. Distal arthrogryposis affects more than 1/10 000 people worldwide, with some of the forms being syndromic. Distal arthrogryposis can be caused by mutations in several genes. Type 1 is mostly due to altered TPM2, MYBPC1 or TNNT3 genes. In some cases, the genetic cause of distal arthrogryposis type 1 currently remains unknown. Type 2 A (Freeman-Sheldon syndrome) and type 2B (Sheldon-Hall syndrome; based on mutated MYH3, TNNI2, TNNT3 or TPM2 genes) mainly show prominent facial features in addition to other symptoms. PIEZO2 mutations are responsible for 3 other forms and Marden-Walker syndrome, whereas ECEL1 alterations cause only one of these forms. Congenital contracture arachnodactyly encompasses a broad phenotypic spectrum (some with rarer symptoms) based on FBN2 variations. However, in some cases, the genetic cause of distal arthrogryposis remains unexplained. Therefore, a negative DNA test result does not exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1386/

• Alias: Arthrogryposis multiplex congenita
• Alias: Congenital contractural arachnodactyly [better expr. than] distal arthrogryposis
• Allelic: Avascular necrosis of femoral head, primary, 2 (TRPV4)
• Allelic: Brachyolmia type 3 (TRPV4)
• Allelic: CAP myopathy 2 (TPM2)
• Allelic: Cardiomyopathy, dilated, 1S (MYH7)
• Allelic: Cardiomyopathy, familial hypertrophic, 26 (FLNC)
• Allelic: Cardiomyopathy, familial restrictive 5 (FLNC)
• Allelic: Cardiomyopathy, hypertrophic, 1 (MYH7)
• Allelic: Contractural arachnodactyly, congenital (FBN2)
• Allelic: Digital arthropathy-brachydactyly, familial (TRPV4)
• Allelic: Hereditary motor + sensory neuropathy, type IIc (TRPV4)
• Allelic: Laing distal myopathy (MYH7)
• Allelic: Left ventricular noncompaction 5 (MYH)
• Allelic: Macular degeneration, early-onset (FBN2)
• Allelic: Metatropic dysplasia (TRPV4)
• Allelic: Myopathy, congenital, with tremor (MYBPC1)
• Allelic: Myopathy, myosin storage, AD + AR (MYH7)
• Allelic: Nemaline myopathy 4, AD (TPM2)
• Allelic: Neuronopathy, distal hereditary motor, type VIII (TRPV4)
• Allelic: Parastremmatic dwarfism (TRPV4)
• Allelic: Scapuloperoneal spinal muscular atrophy (TRPV4)
• Allelic: Scapuloperoneal syndrome, myopathic type (MYH7)
• Allelic: Sodium serum level QTL 1 (TRPV4)
• Allelic: Spondyloepiphyseal dysplasia, Maroteaux type (TRPV4)
• Allelic: Spondylometaphyseal dysplasia, Kozlowski type (TRPV4)
• Allelic: Trismus-pseudocamptodactyly syndrome (MYH8)
• Arthrogryposis, distal, type 1A (TPM2)
• Arthrogryposis, distal, type 1B (MYBPC1)
• Arthrogryposis, distal, type 1C (MYLPF)
• Arthrogryposis, distal, type 2A + B3 (MYH3)
• Arthrogryposis, distal, type 2B1 (TNNI2)
• Arthrogryposis, distal, type 2B2 (TNNT3)
• Arthrogryposis, distal, type 2B4 (TPM2)
• Arthrogryposis, distal, type 3 + 5 (PIEZO2)
• Arthrogryposis, distal, type 5D (ECEL1)
• Arthrogryposis, distal, with impaired proprioception + touch (PIEZO2)
• Carney complex variant (MYH8)
• Congenital distal spinal muscular atrophy + arthrogryposis [Lit.] (TRPV4)
• Contractural arachnodactyly, congenital (FBN2)
• Contractures, pterygia + spondylocarpostarsal fusion syndrome 1A + 1B (MYH3)
• Distal arthrogryposis (MYBPC1)
• Lethal congenital contracture syndrome 4 (MYBPC1)
• Marden-Walker syndrome (PIEZO2)
• Muscular dystrophy, Ar, with rigid spine + distal joint contractures (TOR1AIP1)
• Myopathy, distal, 4 (FLNC)
• Myopathy, myofibrillar, 5 (FLNC)
• Trismus-pseudocamptodactyly syndrome (arthrogryposis, distal, type 7 (MYH8)