Arthrogryposis Differential Diagnoses

Updated: Aug 30, 2021
  • Author: Mithilesh Kumar Lal, MD, MBBS, MRCP, FRCPCH, MRCPCH(UK); Chief Editor: Maria Descartes, MD  more...
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Diagnostic Considerations

Disorders characterized mainly by limb involvement [13]

Amyoplasia (classic arthrogryposis) [8, 14]

This is characterized as follows:

  • The most common type of arthrogryposis seen in clinical practice and constitutes about one third of cases

  • The incidence is about 1 in 10,000 live births

  • Amyoplasia is a sporadic condition and has not been observed in siblings or offspring

  • The pathogenesis is thought to involve impaired blood circulation to the fetus early in pregnancy; hypotension and hypoxia damage the anterior horn cells, resulting in a lack or underdevelopment of muscle tissue, with fatty or connective tissue replacement

  • Symmetrical limb involvement is noted

  • The distinct positioning of the body includes internally rotated and adducted shoulders; fixed, extended elbows; pronated forearms; and flexed wrists and fingers

  • A severe talipes equinovarus deformity with either flexed or extended knees may be present

  • Hips may be flexed and externally rotated or extended and subluxated or dislocated

  • Characteristic midline facial hemangioma is often noted

  • Intelligence is normal

The natural history of untreated amyoplasia is largely undocumented and unknown. However, a study documented a 94% rate of survival for individuals with amyoplasia at 20 years. [4] Without treatment, the ambulatory and functional outcomes are poor.

Distal arthrogryposes

These involve the distal joints and include the following types and subtypes (all have autosomal dominant inheritance with reduced penetrance and variable expressivity) [15] :

  • Type I (Distotarlar dysmorphism) - Adducted thumbs, ulnar deviation of metacarpophalangeal (MP) joints, normal facies

  • Type IIA (Freeman-Sheldon syndrome, whistling face syndrome, craniocarpal tarsal dystrophy, windmill hand) - Distinctive facies, flexion and ulnar deviation of the fingers

  • Type IIB - Distinctive facies, flexion and ulnar deviation of the fingers, vertical talus

  • Type III (Gordon syndrome) - Cleft palate, finger contractures, clubfoot

  • Type IV - Scoliosis, finger contractures

  • Type V - Limited ocular motility, ptosis, finger contractures

  • Type VI - Sensorineural hearing loss, finger contractures

  • Type VII (trismus-pseudocamptylodactyly syndrome, Hecht syndrome) - Inability to fully open mouth, facultative camptodactyly

  • Type VIII (Dominant pterygium syndrome) - Multiple pterygium, finger contractures

  • Type IX (congenital contractual arachnodactyly, Beals syndrome) - Ear deformity, finger contractures

Bony fusion

This is likely to be confused with arthrogryposis but includes symphalangism (ie, fusion of phalanges), coalition (ie, fusion of the carpals and tarsal bones), and synostosis (ie, fusion of long bones).

Contractural arachnodactyly (Beals syndrome; OMIM 121050)

This is an autosomal dominant disorder characterized by joint contractures; a long, thin body build; and crumpling ears. It usually lacks the cardiovascular and ocular abnormalities of Marfan syndrome.


Other associated syndromes and conditions include absence of dermal ridges, absence of distal interphalangeal joint (DIP) creases, amniotic bands, antecubital webbing, camptodactyly, coalition, humeroradial synostosis, familial impaired pronation and supination of forearm, Liebenberg syndrome, nail-patella syndrome, Nievergelt-Pearlman syndrome, Poland anomaly, radioulnar synostosis, symphalangism, symphalangism-brachydactyly, Tel-Hashomer camptodactyly, and trismus pseudocamptodactyly.

Disorders that involve the limbs and other body parts [13]

Multiple pterygium syndrome

Multiple pterygium syndrome is heterogeneous (OMIM 265000, autosomal recessive; OMIM 178100, autosomal dominant). [16, 17] It is characterized as follows:

  • The autosomal recessive type is characterized by multiple joint contractures with marked pterygia, dysmorphic facies (flat, sad, motionless facial appearance), and cervical vertebral anomalies

  • The autosomal dominant type is characterized by multiple pterygia with or without intellectual disability

  • Multiple pterygium syndrome, characterized by pterygia with flexion contractures, scoliosis, and cleft palate, has been reported in several families and is associated with malignant hyperthermia

  • Multiple pterygium syndrome, Escobar type is characterized by webbing of the neck that increases with age, webbing of the knees and elbows that develops before adolescence, multiple joint contractures, and lumbar lordosis [18]

Lethal multiple pterygium syndrome (OMIM 253290) [19]

This is an autosomal recessive disorder characterized by early death, hydrops, cystic hygroma, dysmorphic facies (eg, hypertelorism, markedly flattened nasal bridge with hypoplastic nasal alae, cleft palate, micrognathia, low-set ears), marked webbing and flexion contractures of multiple joints, short neck, small chest, and hypoplastic lungs.

Classification by Hall [19, 20] and Entezami et al [21, 22] is as follows:

  • Type I (Gillin-Pryse-Davis syndrome): Multiple pterygia, pulmonary hypoplasia, genital anomalies, and marked flexed extremities with a reduced muscle mass

  • Type II (Chen syndrome) [23] : Multiple pterygia, hygroma colli, facial anomalies, undermodeled long bones, cartilaginous fusion of joints and bony fusion of the spinous processes of the vertebrae, polyhydramnios, hypoplastic lungs and heart, and diaphragmatic hernia

  • Type III (van Regemorter syndrome): Multiple pterygia, pulmonary hypoplasia, facial anomalies, thin extremities with reduced muscle mass, and fusions of the long tubular bones

  • Type IV (Herva syndrome): Multiple pterygia, degeneration of the anterior horn cells of the spinal cord, and observed particularly in Finland

Popliteal pterygium syndrome (OMIM 119500)

This is an autosomal dominant disorder characterized by popliteal webs, cleft lip or palate, webs in the mouth, and unusual nails.

Lethal popliteal pterygium syndrome (OMIM 263650)

This is also known as Bartsocas-Papas syndrome and is an autosomal recessive disorder characterized by severe webs across the knee. In the newborn period, it is associated with facial clefting and fused digits (synostosis of the hand and foot bones). It is usually lethal.

Freeman-Sheldon syndrome (OMIM 193700)

This is also known as whistling face syndrome and is an autosomal dominant disorder. It is characterized by a masklike face with a small mouth, giving a whistling face appearance; deep-set eyes; small nose with a broad nasal bridge; epicanthal folds; strabismus; high arched palate; small tongue; an H-shaped cutaneous dimpling on the chin; flexion of fingers; equinovarus feet with contracted toes; kyphosis; scoliosis; and other anomalies. [24]


This is known to have associated congenital contractures, including metatropic dysplasia, perinatal lethal osteogenesis imperfecta, parastremmatic dysplasia, Jansen metaphyseal dysplasia, Saul-Wilson syndrome, geleophysic syndrome, synspondylism, spondyloepiphyseal dysplasia congenita, and otospondylomegaepiphyseal dysplasia.


Other associated syndromes and conditions include focal femoral dysplasia, hand-muscle wasting and sensorineural deafness, Holt-Oram syndrome, Kuskokwim syndrome, Larsen dysplasia, leprechaunism, megalocornea with multiple skeletal anomalies, Möbius syndrome, nemaline myopathy, oculodentodigital syndrome, ophthalmomandibulomelic dysplasia, orocraniodigital syndrome, otopalatodigital syndrome, Pfeiffer syndrome, Prader-Willi habitus/osteoporosis/hand contractures, pseudothalidomide syndrome, Puretic-Murray syndrome, sacral agenesis, Schwartz-Jampel syndrome, tuberous sclerosis, VATER (vertebral [defects], [imperforate] anus, tracheoesophageal [fistula], radial and renal [dysplasia]) complex, Weaver syndrome, Winchester syndrome, and X-trapezoidocephaly with midfacial hypoplasia and cartilage abnormalities.

A link exists between a variety of mitochondrial respiratory chain complex deficiencies and contractures of varying severity. Therefore, the differential diagnosis of neonatal arthrogryposis should include mitochondrial disorders, especially if the patient displays other characteristic findings, such as lactic acidemia or basal ganglia abnormalities. [25]

Disorders with limb involvement and CNS dysfunction [13]

These include the following:

  • Associated chromosome abnormalities include 45,X; 47,XXY; 48,XXXY; 49,XXXXX; 49,XXXXY; trisomies (4p, 8, 8 mosaicism, 9, 9q, 10p, 10q, 11q, 13, 14, 15, 18, 21); and many others

  • Cerebrooculofacioskeletal syndrome (OMIM 214150) is a common lethal condition characterized by contractures, brain anomalies, dysmyelination, microphthalmia, cataracts, renal anomalies, and other visceral anomalies

  • Neu-Laxova syndrome (OMIM 256520) is a lethal autosomal recessive disorder characterized by dramatic contractures, intrauterine growth retardation, microcephaly, open eyes, tight ichthyotic skin, and severe CNS anomalies

  • Restrictive dermopathy (OMIM 275210) is a lethal autosomal recessive disorder characterized by contractures and failure of fetal skin to grow normally; this restricts fetal movement, leading to secondary contractures

  • Pena-Shokeir phenotype (OMIM 208150) is characterized by pulmonary hypoplasia, intrauterine growth retardation, polyhydramnios, short umbilical cord, unusual craniofacies, and short, fixed limbs; phenotype is caused by fetal akinesia rather than a specific syndrome [26, 27, 22, 28]

Other associated syndromes and conditions

These include the following:

  • Adducted thumbs

  • Bowen-Conradi syndrome

  • C syndrome

  • Syndrome of cloudy cornea, diaphragmatic defects, and distal limb deformities

  • Syndrome of craniofacial and brain anomalies and intrauterine growth retardation

  • Syndrome of cryptorchidism, chest deformity, and contractures

  • Faciocardiomelic syndrome

  • FG syndrome

  • Maternal multiple sclerosis

  • Maternal autoantibodies

  • Marden-Walker syndrome

  • Meckel syndrome

  • Meningomyelocele

  • Mietens syndrome

  • Miller-Dieker syndrome

  • Congenital myotonic dystrophy

  • Congenital myasthenia gravis

  • Popliteal pterygium with facial clefts

  • Pseudotrisomy 18

  • Spinal muscular atrophy

  • Toriello-Bauserman syndrome

  • X-linked lethal arthrogryposis

  • Zellweger syndrome