Prenatal Detection of HSPG2-Related Dyssegmental Dysplasia, Silverman-Handmaker Type: A Rare Case Report

HSPG2-related dyssegmental dysplasia (heparan sulfate proteoglycan 2) is an extremely rare and severe autosomal recessive skeletal dysplasia. The low incidence and the overlapping features with other types of lethal skeletal dysplasia represent the main challenges in diagnosis. Early diagnosis is essential and can be achieved by ultrasound examination and genetic analysis. This report describes a case of HSPG2-related dyssegmental dysplasia, Silverman-Handmaker type (DDSH) diagnosed prenatally through a combination of detailed ultrasound imaging and subsequent genetic analysis.

A 21-year-old pregnant lady (G2P1) was referred to our center at 17-week gestation upon the detection of severe shortening of fetal limbs. Detailed ultrasound examination revealed small for gestational age, and specific craniofacial features such as severe micrognathia, short neck, microcephaly, prominent eyes, and occipital encephalocele. Other abnormalities were detected in extremities in the form of bowing of lower limbs, severe tetramicromelia, and upper limbs in a fixed flexion. Amniocentesis for whole exome sequencing was performed. It showed a homozygous pathogenic variant in the HSPG2 gene (c.11565+1G>A), a result consistent with the genetic diagnosis of autosomal recessive HSPG2-related DDSH. Medical termination was performed based on the decision of parents. Parents signed a written consent for the publication of this case report.

Findings of this report support the growing evidence of the phenotypic spectrum and genetic underpinnings of the lethal disorder of HSPG2-related DDSH, emphasizing the importance of early and accurate diagnosis for optimal patient care. DDSH can be diagnosed prenatally using fetal ultrasound as early as 13 weeks. Radiographic assessment and molecular analysis of the HSPG2 gene are essential for confirming the prenatal diagnosis. Accurate diagnosis enables appropriate healthcare delivery and facilitates informed reproductive decision-making, including prenatal diagnosis and preimplantation genetic testing in future pregnancies.