Prenatal diagnosis of Smith-Lemli-Opitz syndrome

Objective

To present a case of Smith Lemli Opitz Syndrome (SLOS) associated with multiple anomalies and to discuss the prenatal diagnosis.

Methods

We present a case of SLOS in which multiple anomalies were detected ultrasonographically. SLOS is an autosomal recessive deficiency of 7-dehydrocholesterol reductase (DHCR7) resulting in an accumulation of 7- and 8-dehydrocholesterol (7- and 8-DHC) in tissues and body fluids. At birth patients have variable malformations of central nervous system, heart, kidney, genitalia, and limbs. These malformations may be life-threatening. Psychomotor and mental retardation and behavior abnormalities become evident later. Prenatally SLOS can be suspected with the findings of malformations and intrauterine growth retardation (IUGR) in prenatal ultrasonography and reduced maternal free estriol in serum. The diagnosis is confirmed by sterol analysis in a chorionic villus biopsy or amniotic fluid.

Case(s)

A 36-year-old pregnant woman was referred to our institution at the 27th week of her fifth pregnancy because of fetal cardiac anomaly. Her first and third pregnancies had ended up with healthy male and female babies delivered vaginally. She had aborted her second pregnancy. The fourth pregnancy was a spontaneous twin pregnancy but at 6th gestational week one of the twins was missed. The surviving twin had short humerus and femur length.This male infant was delivered vaginally with low APGAR scores. He was 3600g and had multisystemic anomalies such as thumb duplication, talipes, congenital cardiac anomaly, adrenal hypoplasia, ambiguous genitalia and small kidneys. He lived only a few days. The patient underwent amniocentesis in the current fifth pregnancy because of the high risk in her second trimester screening test. Normal karyotype was reported. Atrioventriculer septal defect (AVSD), aortic interruption, hypoplastic aorta were observed in fetal echocardiographic evaluation. At the first visit in our institution, left ventricular hypoplasia, left atrial hypoplasia, AVSD, hypoplastic aorta and early intrauterine growth restriction (IUGR) were recognized. Genetic consultation was offered because of the similar findings in the previous baby. Her weekly follow-up continued and cesarean section was performed at the 37th week due to IUGR, oligohydramnios and fetal distress. A 2280g female infant was delivered. Cord blood was sampled to be studied at the genetic department to confirm the prenatal diagnosis. The newborn had metabolic disturbances and also dysmorphologic features such as telangiectasia, rhizomelic limbs. Echocardiographic evaluation was compatible with prenatal findings.

Conclusion

Smith-Lemli-Opitz syndrome (SLOS) can be associated with multiple malformations. Due to reduced maternal serum unconjugated estriol (MSuE3) levels, second trimester screening tests may reveal high risk for chromosomal anomaly. Such patients with poor obstetric history should be referred to genetic consultation.

Keywords

Smith Lemli Opitz Syndrome, prenatal diagnosis