Prenatal diagnosis of lanosterol synthase deficiency: Fetal ultrasound findings as a window on family genetics

Sigal Matza Porges*, Hagar Mor-Shaked, Avraham Shaag, Shay Porat, Hagit Daum

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Cholesterol is essential in the brain from the earliest stages of embryonic development. Disruption of cholesterol synthesis pathways that leads to cholesterol deficiency underlies a few syndromes, including desmosterolosis and Smith–Lemli–Opitz syndrome. In both syndromes, brain anomalies can occur. The LSS gene encodes lanosterol synthase (LSS), an important enzyme in the cholesterol biosynthesis pathway. Biallelic pathogenic variants in this gene cause alopecia–intellectual disability type 4 syndrome (APMR4, MIM 618840), a rare autosomal recessive disorder. Here, we describe two new LSS variants (c.1016C > T; p. Ser339Leu and c.1522G > C; p. Gly508Arg) found in a compound heterozygous fetus diagnosed prenatally with brain abnormalities by ultrasound scanning. Two of his siblings from the same parents also harbored these variants. Both siblings had alopecia, mild intellectual disability, autism spectrum disorder, and cataracts. To the best of our knowledge, this case represents the first prenatal diagnosis of APMR4 first suspected by ultrasound. In addition, the phenotypic features of the siblings are extensive compared with those described in previous reports and include abnormal corpus callosum, cataracts, alopecia, and developmental delay.

Original languageAmerican English
Article number104825
JournalEuropean Journal of Medical Genetics
Issue number10
StatePublished - Oct 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Masson SAS


  • Congenital alopecia
  • Congenital cataracts
  • Exome sequencing
  • LSS pathogenic variant
  • Prenatal diagnosis
  • Ultrasound scanning


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