Arthrogryposis Multiplex Congenita

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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Congenital malformations and deformations of the musculoskeletal system

OMIM Number

108110

Mode of Inheritance

Isolated cases

Description

Arthrogryposis multiplex congenita (AMC) is a frequent sequence of congenital joint fixation. The major cause of arthrogryposis is fetal akinesia (decreased fetal movements), which could result from fetal abnormalities (e.g., neurogenic, muscle, and connective tissue abnormalities) or maternal disorders (e.g., infection, drugs, and trauma). AMC is characterized by reduced mobility of many joints of the body due to the overgrowth of fibrous tissue in the joints (fibrous ankylosis). The symptoms of arthrogryposis multiplex congenita vary widely among affected individuals depending on the disease type. In the most common form of the disease, the range of motion of the joints in the limbs is limited or fixed.

The disease occurs in 1/3000 live births and has been ascribed to either oligohydramnios or a variety of diseases involving the central nervous system, skeletal muscle, or spinal cord. Since neuronal degeneration and neuronophagia occur in the anterior horns, it has been hypothesized that the AMC of neurogenic origin could be related to acute spinal muscular atrophy (SMA type I, Werdnig-Hoffmann disease). Life span is usually normal, but it may be depend on the disease severity and associated malformations.

Molecular Genetics

Most types of arthrogryposis multiplex congenita are not inherited and do not occur more than once in a family. A genetic cause is only identified in about 30% of the cases.

Epidemiology in the Arab World

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Other Reports

Oman

Aithala et al. (1995) reported the co-occurrence of spinal muscular atrophy (SMA) with arthrogryposis multiplex congenita in monozygotic male twins who were the product of a consanguineous marriage. They presented at the age of three and a half months with a history of generalized weakness and delayed gross motor milestones. There was no significant family history of still births, abortions, neurological disorders, or joint contractures. At birth, the twins had good apgar scores, but were noted to have contractures. The twins presented with weights below the 10th and 3rd centile, severe generalized hypotonia and wasting of the proximal and distal groups of limb muscles, along with symmetrical distal joint flexion contractures, obvious fasiculations of the tongue during sleep and activity, paradoxical respiratory movements, and mild spinal scoliosis. The other organ systems were normal. Blood investigations revealed normal creatinine phosphokinase and lactate dehydrogenase. EMG revealed denervation, increased insertional activity, and fibrillations with polyphasic potentials. Histopathology of muscle biopsy of one of the twins showed hypertrophied fibers intermingled with atrophic ones. ATP staining was consistent with neurogenic atrophy. The twins were then diagnosed to have infantile SMA and distal arthrogryposis. They died at the age of eight months from severe pneumonia. Aithala and colleagues (1995) surmised that these infants might form a separate sub-group as the occurrence of SMA and arthrogryposis has not been seen in the same families as classic SMA disease. In the absence of necropsy studies, further validation of this proposal could not be done. [Aithala GR, Chand P, Koelma I, El Bualy MS. Acute infantile spinal muscular atrophy with arthrogryposis multiplex congenita in identical twins. Emirates Med J. 1995; 13:53-5.]

Rajab et al. (2005) reported six Omani children from two consanguineous families, with a multiple congenital anomaly syndrome defined by arthrogryposis multiplex congenita, typical facial appearance, ophthalmologic anomalies, atrophic calf muscles, and interdigital, neck and axillar pterygia. In addition, the patients had unique features as a furrowed tongue and enlarged corneal nerves, undescribed previously in association with other distal arhtrogryposis syndromes (DA). Rajab et al. (2005) suggested that their patients could be classified as having Escobar syndrome type B because of the apparently recessive inheritance, short stature, relative macrocephaly, distinct facial appearance, camptodactyly, congenital foot deformities, and similar skeletal abnormalities such as vertebral defects, scoliosis, and joint dislocations.

Saudi Arabia

Abdullah et al. (2000) reported for the first time in the Arabian Gulf area three patients with arthrogryposis multiplex congenita, cholestasis and renal tubular dysfunction from a Saudi family with two other siblings and three cousins who possibly died with a similar clinical picture. The first patient, the 11th for a first degree Saudi cousin parents, presented jaundice at age of 3 days. Liver biopsy reported by showed intracellular and intracanalicular cholestasis with paucity of intrahepatic bile ducts. Many hepatocytes showed cytoplasmic granular pigment of indeterminate nature and there was no evidence of metabolic or storage disease. She was hyptonic with marked generalized muscle wasting, bilaterally dislocated hips, talipes equinovarus deformity and flexion deformities of the knees. By the fifth month she had severe global developmental delay. MRI brain at the age of 150 days showed hypoplasia of the corpus callosum, with insufficient myelination. Electromyography was consistent with muscular atrophy. The child had polyuria renal tubular acidosis, glucosuria, phosphaturia, hypophosphatemia, hyperchloremia, generalized aminoaciduria and proteinuria. The second case was a female baby, the sister of case 1, and had bilateral hip dislocation, knees flexion and talipes equinovarus. The third case was a female infant, sister of case 1, and was noticed to have flexion deformity of both knees and dislocated right hip at birth. She developed direct hyperbilirubinenia at age of 3 days. Abdullah et al. (2000) pointed that this autosomal recessive disorder is possibly under-diagnosed in the Arabian Gulf region, characterized by a high consanguineous marriage rate.

United Arab Emirates

Sztriha et al. (1998) reported an inbred Arab family with three neonates affected by microlissencephaly syndrome. The index patient was a male infant born by Cesarean section because of fetal distress. The parents were consanguineous of United Arab Emirates origin. Pregnancy was complicated by gestational diabetes requiring insulin treatment. On examination, he had gasping respiration. He died 10 hours after birth. Brain magnetic resonance imaging in the index case revealed very thin brain mantle with agyria-pachygyria, agenesis of the corpus callosum, and hypoplasia of the brainstem and cerebellum. Two male siblings also died soon after birth. All three neonates had microcephaly, arthrogryposis multiplex congenita, and micropenis.

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