Absent inner dynein arms in a fetus with familial hydrocephalus-situs abnormality.
We report a family in which a healthy, unrelated couple had a male fetus with bilateral ventriculomegaly, a normal liveborn girl, a hydatidiform molar pregnancy, a female fetus with ventriculomegaly and situs abnormalities, and a male fetus with hydrocephalus, a three-lobed left lung, and defective tracheal cilia with absent inner dynein arms and a single centriole. A mutation analysis of FOXJ1 and POLL in the last fetus with ciliary defect revealed no mutation within their coding regions. The presence of three affected fetuses of both sexes in a family with phenotypically normal parents suggests that the condition was inherited as an autosomal recessive trait. A thorough evaluation of the thoracic and abdominal situs is recommended before counseling a family of a child with hydrocephalus, because the recognition of situs defects may point to the diagnosis of primary ciliary defect and recurrence risk of 25% for siblings. This figure is much higher than the general risk of 1-2% for siblings of a patient with isolated hydrocephalus.
Kosaki
Kenjiro
K
Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan. kkosaki@sc.itc.keio.ac.jp
Ikeda
Kazushige
K
Miyakoshi
Kei
K
Ueno
Mari
M
Kosaki
Rika
R
Takahashi
Daisuke
D
Tanaka
Mamoru
M
Torikata
Chikao
C
Yoshimura
Yasunori
Y
Takahashi
Takao
T
D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology*; D037881:Aborted Fetus; D002552:Cerebral Ventricles / Q000002:abnormalities*; D002923:Cilia / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics; D004398:Dyneins / Q000737:chemistry*; D017809:Fatal Outcome; D051858:Forkhead Transcription Factors; D006801:Humans; D006849:Hydrocephalus / Q000473:pathology*; D007619:Kartagener Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D017422:Sequence Analysis, DNA; D012857:Situs Inversus / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics
D004268:DNA-Binding Proteins; C106349:FOXJ1 protein, human; D051858:Forkhead Transcription Factors; D015534:Trans-Activators; D004398:Dyneins