Fetal akinesia deformation sequence: a study of 30 consecutive in utero diagnoses.

The etiology of the fetal akinesia deformation sequence (FADS) is heterogeneous and can be the result of neurogenic and myopathic disorders, restrictive dermopathy, teratogen exposure, and intrauterine constraint. We present the prenatal and fetopathological findings in a consecutive series of 30 affected fetuses with normal chromosomal results. According to the in utero time of onset of the fetal akinesia, the severity of the phenotype varied from a severe, generalized FADS in the early-onset group to milder defects, as isolated distal arthrogryposis in the late-onset group. No more than 10% (3/30) were diagnosed in the first trimester of pregnancy and all presented a severe phenotype. Twenty-seven of the thirty (90%) were diagnosed after the first trimester, with a severe FADS in 15/27 and a milder phenotype of distal arthrogryposis in 12/27. In all 30 patients, extensive neuropathological studies (brain, spinal cord, and muscles) were performed. In 16 patients (53%) a specific diagnosis could be made (central nervous system abnormalities 9/16; spinal cord 1/16; primary myopathy 3/16; syndromic 3/16). In 10 others (33%), pathological neuromuscular findings were present but no definitive diagnosis was established. In 4 patients (13%), neuromuscular findings were normal, and the etiology of the FADS remained unexplained.

[1]  S. Reed,et al.  Three distinct types of X‐linked arthrogryposis seen in 6 families , 1982, Clinical genetics.

[2]  C. Morris,et al.  Prenatal diagnosis of distal arthrogryposis. , 1988, American journal of medical genetics.

[3]  J. Fryns,et al.  Non-immune hydrops fetalis caused by beta-glucuronidase deficiency (mucopolysaccharidosis VII). Study of a family with 3 affected siblings. , 1996, Genetic counseling.

[4]  L. de Catte,et al.  β‐Glucuronidase deficiency as a cause of prenatally diagnosed non‐immune hydrops fetalis , 1991 .

[5]  A. Munnich,et al.  Survival motor neuron gene deletion in the arthrogryposis multiplex congenita-spinal muscular atrophy association. , 1996, The Journal of clinical investigation.

[6]  J. Hall,et al.  Analysis of Pena Shokeir phenotype. , 1986, American journal of medical genetics.

[7]  K. Devriendt,et al.  Clinical and molecular genetic features of congenital spinal muscular atrophy , 1996, Annals of neurology.

[8]  G. Lingman,et al.  Mucopolysaccharidosis VII as cause of fetal hydrops in early pregnancy. , 1992, American journal of medical genetics.

[9]  J. Fryns,et al.  The fetal akinesia deformation sequence. A fetopathological approach. , 1990, Genetic counseling.

[10]  W. Kleijer,et al.  beta-Glucuronidase deficiency as a cause of fetal hydrops. , 1992, American journal of medical genetics.

[11]  J. Fryns,et al.  Fetal akinesia sequence caused by glycogenosis type VII. , 1995, Genetic counseling.

[12]  S. Reed,et al.  The distal arthrogryposes: delineation of new entities--review and nosologic discussion. , 1982, American journal of medical genetics.

[13]  J. Fryns,et al.  Marden—Walker syndrome versus isolated distal arthrogryposis: Evidence that both conditions may be variable manifestations of the same mutated gene , 1998, Clinical genetics.

[14]  P. Barth,et al.  Olivo-ponto-cerebellar atrophy with muscular atrophy, joint contractures and pulmonary hypoplasia of prenatal onset , 2004, Virchows Archiv A.

[15]  D. Armstrong,et al.  Fatal infantile encephalopathy with olivopontocerebellar hypoplasia and micrencephaly , 2004, Acta Neuropathologica.

[16]  E. Jauniaux,et al.  Lysosomal storage diseases presenting as transient or persistent hydrops fetalis. , 1991, Genetic counseling.

[17]  K. Devriendt,et al.  Two siblings with early onset fetal akinesia deformation sequence and hydranencephaly: further evidence for autosomal recessive inheritance of hydranencephaly, fowler type. , 2002, American journal of medical genetics.