Evidence of intrauterine growth restriction and growth hormone deficiency in 49,XXXXY syndrome

• Published in: American journal of medical genetics. Part A 2021-12, Vol.185 (12), p.3547-3553
• Main Authors: Counts, Debra R., Yu, Christine, Lasutschinkow, Patricia C., Sadeghin, Teresa, Gropman, Andrea, Samango‐Sprouse, Carole A.
• Format: Article
• Language: English
• Subjects: 49,XXXXY; Anthropometry; Child; Child, Preschool; Children; Chromosomes, Human, X - genetics; Chromosomes, Human, Y - genetics; Dwarfism, Pituitary - complications; Dwarfism, Pituitary - diagnostic imaging; Dwarfism, Pituitary - genetics; Dwarfism, Pituitary - physiopathology; Etiology; Fetal Growth Retardation - diagnostic imaging; Fetal Growth Retardation - genetics; Fetal Growth Retardation - physiopathology; Growth Hormone - deficiency; Growth Hormone - genetics; Growth hormones; Humans; Infant; Infant, Newborn; intrauterine growth restriction; Klinefelter Syndrome - complications; Klinefelter Syndrome - diagnostic imaging; Klinefelter Syndrome - genetics; Klinefelter Syndrome - physiopathology; Male; Physical growth; Sex Chromosome Aberrations; sex chromosome abnormalities and aneuploidies; Short Stature Homeobox Protein - genetics; X and Y chromosomal variations
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.61738

49,XXXXY is an X and Y chromosome variation that occurs in 1:85,000 to 1:100,000 live male births. Previous case studies have described boys with this disorder to be shorter than average when compared with boys with only one extra chromosome and with the mean stature in a small cohort reported to range from the seventh to 33rd percentile. The origin behind the possible differences in height between boys with 47,XXY and 49,XXXXY is currently unknown, however one study hypothesized that it was due to a difference in the expression of the SHOX gene. This study reports on the anthropometric measurements of 84 boys with 49,XXXXY. Forty‐five percent of children with 49,XXXXY were found to be below the third percentile in height at the time of evaluation. In addition, 7.14% of the cohort were diagnosed and given treatment for growth hormone deficiency (GHD). The analysis of this cohort demonstrates that the below average heights seen throughout childhood in this population potentially begins prenatally and suggests that boys with 49,XXXXY may be at a higher risk for intrauterine growth restriction (IUGR) and GHD. Future research is needed to investigate the etiology of the poor growth in boys with 49,XXXXY and evaluate the incidence of GHD and IUGR in this population.