Prenatal diagnosis of Ritscher-Schinzel syndrome
Purpose: Utilize prior pregnancy history and fetal ultrasound findings to provide a basis for genetic diagnosis.
Methods: Family and pregnancy history, fetal ultrasound, echocardiogram, cytogenetic evaluation, fluorescence in situ hybridization (FISH) and autopsy.
Results: The first pregnancy of a healthy, unrelated couple was terminated at 18 weeks gestation due to ultrasound findings of cystic hygroma, Dandy-Walker variant, tetralogy of Fallot with absent pulmonary valve, single umbilical artery (SUA) and absent kidney. Cytogenetic analysis showed a normal male karyotype. FISH showed no deletion or duplication of chromosomal region 22q11.2. Subsequent pregnancy was again characterized by increased nuchal lucency at 11 weeks 3 days. Abnormal head shape, single umbilical artery and possible heart defect were noted at 14 weeks. Fetal echocardiogram at 14 weeks 2 days showed levorotation, absent pulmonary valve, dilated and pulsatile branch pulmonary arteries, tricuspid insufficiency, and possible hypoplastic left heart. Pregnancy was terminated. Additional findings on autopsy included low set ears, micrognathia, intestinal malrotation, proximally placed thumbs and club feet. These malformations suggested Ritscher-Schinzel syndrome, an autosomal recessive multiple malformation/mental retardation syndrome of unknown etiology, which may be more common than previously thought. Typical features include DWM, hydrocephalus, characteristic facial dysmorphism, ocular colobomata, cleft palate, conotruncal or endocardial cushion defects, SUA, renal anomaly, hypospadias, ano-rectal malformation, minor skeletal defects, postnatal growth deficiency and immunodeficiency.
Conclusions: Specific pattern of malformation suggested diagnosis of Ritscher-Schinzel syndrome in two affected fetuses despite absence of an affected liveborn child. Consider this condition in any fetus with Dandy-Walker malformation and/or conotruncal or endocardial cushion defect and normal karyotype.