Inheritance: autosomal recessive
Genetic locus: 11q12-13
Biochemical defect: deficiency of 7-dehydrocholesterol reductase (DHCR7) which affects cholesterol synthesis
Clinical features:
(1) small size at birth, with failure to thrive
(2) moderate short stature
(3) facial dysmorphic features
(3a) cleft palate
(3b) anteverted nostrils with broad nasal tip
(3c) ptosis of the eyelids
(3d) microcephaly
(3e) micrognathia
(3f) low set or slanted auricles
(3g) strabismus
(4) congenital heart disease (hypoplastic left heart, atrial septal defect, patent ductus arteriosus, membranous ventricular septal defect, endocardial cushion defect)
(5) in males, hypospadias, micropenis, bifid scrotum or cryptorchidism
(6) defects in limbs
(6a) polydactyly
(6b) syndactyly (typically of the second and third toes)
(6c) short, proximally placed thumb
(7) mental deficiency
(8) feeding difficulty with gastroesophageal reflux
(9) muscle hypotonia in early infancy, with hypertonia developing later
(10) renal abnormality (ureteropelvic junction obstruction, hydronephrosis, cystic dysplasia, renal agenesis, other)
Laboratory findings:
(1) very low serum cholesterol
(2) elevated 7-dehydrocholesterol
(3) absence of unconjugated estriol in amniotic fluid
