Pierson Syndrome: A Fetal Homozygous Pathogenic Variant Within the LAMB2 Gene

Document Type

Conference Proceeding

Publication Date

2025

Publication Title

Genetics in Medicine Open

Abstract

Treatment and Management: Serial ultrasounds to monitor growth, amniotic fluid levels, and the fetal kidneys were recommended. Throughout the prenatal period, the patient received an initial course of antenatal steroids at 29 weeks 3 days gestation and a rescue course at 31 weeks 4 days gestation due to concerns regarding non-reassuring antenatal testing. After diagnosis of Pierson syndrome, consultation by pediatric nephrology, neonatology, and the palliative care teams were requested. Due to the suspected life-limiting effects of the disease, the patient opted to pursue comfort care. Outcome and Follow-Up: The patient ultimately underwent a scheduled induction of labor at 36 weeks 2 days gestation that resulted in a technically uncomplicated spontaneous vaginal delivery. APGAR score at 1 minute was 6 and at 5 minutes was 8. In alignment with the patient’s wishes, comfort care was provided to the infant. The infant passed at approximately 12 hours of life. Discussion: It is suspected that the cnLOH likely contributed to this affected pregnancy. PS has been reported to have highly variable presentations and prior published case reports have not previously described a homozygous c.1477del p.(C493Afs*4) pathogenic variant, which proved to have a severe life-limitng phenotype. Conclusion: Case reports such as this one continue to add to the body of knowledge needed to make informed phenotype-genotype correlations. This information remains essential when counseling patients regarding expected outcomes, goals of care, and desired clinical management in these challenging situations. Introduction: Pierson syndrome (PS) is a rare autosomal recessive disorder caused by variants within the LAMB2 gene. LAMB2 encodes laminin beta 2, which is a protein expressed within the glomerulus, neuromuscular junction and various portions of the eye leading to congenital nephrotic syndrome and ocular defects. The phenotype severity has been shown to be dependent on underlying genetic abnormality. This report presents a novel case of a fetus found to be homozygous for the pathogenic variant c.1477del p.(C493Afs*4) in LAMB2 leading to life-limiting Pierson syndrome. Case Presentation: A 30-year-old nulliparous patient was referred to genetic counseling at 23 weeks 6 days gestation for findings of bilateral hyperechogenic kidneys identified on anatomy ultrasound. There was no significant maternal or paternal past medical history. Family history was negative for birth defects, intellectual disabilities, developmental delays, multiple miscarriages, or known genetic abnormalities. The couple denied consanguinity. There was a low risk cfDNA obtained in the first trimester. A repeated detailed anatomy ultrasound confirmed that bilateral kidneys were diffusely hyperechogenic. Both kidneys had a normal contour, were slightly smaller in size, and did not have evidence of cysts. The fetal bladder was present, and no other anatomical abnormalities were appreciated. Fetal growth restriction with estimated fetal weight in 7th percentile and oligohydramnios were initially diagnosed at 29 weeks 3 days gestation. The fetus continued to have inadequate growth and ultimately was diagnosed with anhydramnios at 31 weeks 4 days. At the time of delivery, the estimated fetal weight was in the 1st percentile. There was a normal umbilical artery Doppler interrogation throughout the pregnancy. Diagnostic Workup: An amniocentesis was performed at the time of the initial genetic counseling appointment. Cytomegalovirus and toxoplasmosis PCR were negative. FISH resulted with disomy for chromosomes 13, 18, 21, and sex chromosomes. Microarray results showed a 26.164 Mb copy-neutral loss of heterozygosity (cnLOH) within chromosome bands 3p22.3-3p14.2. Expanded carrier screening for 560 genes of both the patient and her partner were low risk and negative for ARPKD and seven of the 391 genes found in the cnLOH. Exome sequencing results showed both the patient, and her partner, were found to carry the pathogenic variant c.1477del p.(C493Afs*4) in LAMB2 and both copies of the pathogenic variant were inherited by the fetus.

Volume

3

Issue

Suppl 2

First Page

47

Comments

2025 AMCG (American College of Medical Genetics) Annual Clinical Genetics Meeting, March 18-22, 2025, Los Angeles, CA

Last Page

48

DOI

10.1016/j.gimo.2025.103250

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