An Unusual Hydrops Fetalis Associated with Compound Heterozygosity for Krüppel-like Factor 1 mutations

Area of Science:

• Hematology
• Genetics
• Fetal Medicine

Background:

• Hydrops fetalis is a serious fetal condition often caused by Hemoglobin Bart's disease in Southeast Asia.
• Congenital dyserythropoietic anemia (CDA) is a group of inherited disorders characterized by ineffective erythropoiesis.
• Krüppel-like factor 1 (KLF1) gene mutations are known to cause various hematological disorders.

Observation:

• A pregnant woman presented with fetal cardiomegaly detected during a routine mid-trimester scan.
• The fetus developed hydrops fetalis and severe anemia (Hb 3.4 g/dL), with common causes excluded.
• Increased erythroblasts suggested CDA, prompting genetic screening of the parents.

Findings:

• The fetus was found to be compound heterozygous for two novel KLF1 gene mutations: c.525_526insCGGCGCC, p.Gly176Argfs*179 (mother) and c.1012C>A, p.Pro338Thr (father).
• Diagnosis of CDA associated with compound heterozygous KLF1 mutations was confirmed.
• The hydrops fetalis resolved following repeated intrauterine transfusions.

Implications:

• This case highlights that hydrops fetalis can be a rare manifestation of CDA due to compound heterozygous KLF1 mutations.
• Repeated intrauterine transfusions can effectively manage this severe fetal condition.
• The findings expand the known clinical spectrum of KLF1 gene mutations and their impact on erythropoiesis.