fetal akinesia sequence
MIM.208150
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Definition: Prolonged decrease or absence of fetal motion results in a group of anomalies, characterized in their full blown appearance by abnormal limb positions, craniofacial deformations, growth restriction, polyhydramnios, lung hypoplasia and short umbilical cord. The deformities are usually symmetric and the severity of the deformities often increases distally along the involved limb. FADS is usually generalized but focal anomalies exist. Bimelic akinesia affects more often the lower limbs.
Inheritance
autosomal recessive transmission (50%)
autosomal dominant transmission (2070954)
Synopsis
systemic anomalies
- small for gestational age
- intrauterine growth retardation
- premature birth
- stillborn (30%)
craniofacial anomalies
- rigid face (expressionless face)
- long philtrum
- micrognathia
- small, posteriorly rotated ears
- poorly folded ears
- prominent eyes
- hypertelorism
- telecanthus
- short palpebral fissures
- ptosis
- depressed nasal tip
- small mouth
- high arched palate
- cleft palate
- short neck
thoracic anomalies
- pulmonary hypoplasia
- small thorax
- thin ribs
digestive anomalies
- short-gut syndrome
limb anomalies
- hip ankylosis
- elbow ankylosis
- knee ankylosis
- thin, gracile long bones
- ulnar deviation of hands
- camptodactyly
- absent dermal ridges or sparse dermal ridges
- ankle ankylosis
- rocker-bottom feet
- talipes equinovarus
neurological anomalies
- neurogenic muscle atrophy
- hydrocephalus
- microgyria
- cerebellar hypoplasia
- absent septum pellucidum
- cavum septum pellucidum
placental et annexial anomalies
Etiology
FADS can be secondary to neurogenic diseases, myogenic anomalies, and restrictive dermopathies. The most common pattern of transmission is autosomal recessive.
Due to the various possible etiologies, the prediction of recurrence is difficult, varying from 0-15% (when associated with primary brain malformation) to 25% (myogenic etiology).
fetal neuronopathy
- anterior horn cell loss and lateral corticospinal tract degeneration in spinal cord, with marked muscular atrophy (11810649)
fetal myopathy (11555456, 2262870)
- congenital myotonic dystrophy (7606895)
maternal myasthenia gravis (10797415)
fetal cerebral anomalies
- lissencephaly type 3 (MIM.601160)
- severe cerebrospinal malformations
- Dandy-Walker malformation (11810649)
- acquired intrauterine brain damage (1891100)
- bilateral opercular polymicrogyria (8972538)
degeneration of large motor neurons of the thoracolumbosacral spinal cord and irregular atrophy of diaphragm (1866365)
association microphthalmia, hemiatrophy of the left temporal lobe with calcification of degenerated neurons, hypoplasia of the cervothoracic spinal cord with decrease and degeneration of neurons (1866365)
monogenic diseases
- acetylcholine receptor pathway mutations (18252226)
- no mutations in CHRNA1, CHRNB1, CHRND and RAPSN genes(18179903)
Associations
cystic hygroma (11332983)
thymic and systemic T-cell lymphoid hyperplasia (11070126)
Differential diagnosis
- craniofacial, limb, and thoracic anomalies
uterine malformation
References
Michalk A, Stricker S, Becker J, Rupps R, Pantzar T, Miertus J, Botta G, Naretto VG, Janetzki C, Yaqoob N, Ott CE, Seelow D, Wieczorek D, Fiebig B, Wirth B, Hoopmann M, Walther M, Körber F, Blankenburg M, Mundlos S, Heller R, Hoffmann K. Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders. Am J Hum Genet. 2008 Feb;82(2):464-76. PMID: 18252226
Vogt J, Harrison BJ, Spearman H, Cossins J, Vermeer S, ten Cate LN, Morgan NV, Beeson D, Maher ER. Mutation analysis of CHRNA1, CHRNB1, CHRND, and RAPSN genes in multiple pterygium syndrome/fetal akinesia patients. Am J Hum Genet. 2008 Jan;82(1):222-7. PMID: 18179903
Yfantis H, Nonaka D, Castellani R, Harman C, Sun CC. Heterogeneity in fetal akinesia deformation sequence (FADS): autopsy confirmation in three 20-21-week fetuses. Prenat Diagn. 2002 Jan;22(1):42-7. PMID: 11810649