Smith-Lemli-Opitz syndrome is a autosomal recessive malformative syndrome caused by mutations in the sterol delta-7-reductase gene (DHCR7) (MIM.602858), which maps to 11q12-q13.

Synopsis

 systemic anomalies

• short stature
• birth weight <2500gm
• failure to thrive
• decreased fetal movement
• breech presentation

 craniofacial anomalies

• microcephaly
• micrognathia
• bitemporal narrowing
• low-set ears
• posteriorly rotated ears
• ptosis of eyelids
• inner epicanthal folds
• cataracts
• hypertelorism
• strabismus
• anteverted nares
• broad, flat nasal bridge
• cleft palate
• hypoplastic tongue
• broad alveolar margins
• large central front teeth
• dental crowding

 cardiovascular anomalies

• ventricular septal defect
• atrial septal defect
• coarctation of aorta
• patent ductus arteriosus

 pulmonary anomalies

• hypoplastic lungs
• incomplete lobulation of the lungs

 gastrointestinal anomalies

• digestive malrotation
• pyloric stenosis
• digestive aganglionosis (Hirschsprung disease)

 atypical mononuclear giant cells in pancreatic islets

 genital anomalies

• perineoscrotal hypospadias
• ambiguous genitalia
• micropenis
• hypoplastic scrotum
• bifid scrotum
• microurethra
• cryptorchidism

 urinary anomalies

• renal agenesis
• renal hypoplasia
• hydronephrosis
• single kidney
• cystic kidneys (cystic renal disease)
• ureteropelvic junction obstruction
• ureteral anomalies

 limb anomalies

• stippled epiphyses
• hip dislocation
• hip subluxation
• limbs
• limb shortening
• short thumbs
• postaxial polydactyly
• proximally placed thumbs
• syndactyly of second and third toes
• talipes calcaneovalgus
• short, broad toes
• overriding toes
• metatarsus adductus

 cutaneous anomalies

• severe photosensitivity
• eczema
• facial capillary hemangioma
• blonde hair

 central nervous system

• hydrocephalus (dilated ventricles)
• microcephaly
• frontal lobe hypoplasia
• cerebellar hypoplasia
• brainstem hypoplasia
• gray matter periventricular heterotopia
• irregular gyral pattern
• irregular neuronal organization
• anomalies of spinal cord development

Biology

 low cholesterol
 elevated 7-dehydrocholesterol

Phenotypic variants

 Rutledge lethal multiple congenital anomaly syndrome (SLO2) (Ex-MIM.268670)

Etiology

 mutations in the gene DHCR7 encoding sterol delta-7-reductase at 11q12-q13 (MIM.602858)

References

 Herman GE. Disorders of cholesterol biosynthesis : prototypic metabolic malformation syndromes. Hum Mol Genet. 2003 Apr 2 ;12(Suppl 1) :R75-88. PMID : #12668600#

 Farese RV Jr, Herz J. Cholesterol metabolism and embryogenesis. Trends Genet. 1998 Mar ;14(3):115-20. PMID : #9540409#