Objective To investigate the attitudes of parents of children with a sex chromosome aneuploidy (SCA) regarding the impact of an early diagnosis and noninvasive prenatal testing (NIPT). Method A survey consisting of multiple choice and long response formatted questions was completed by parents of children with SCA(s). Results Fifty‐five participants responded to the survey. A total of 88.1% of participants who received an early diagnosis expressed that it had a positive impact on their child's life. Of the 23 participants who utilized NIPT, 95.7% believed it was a decisive factor in their life because they could research the disorders prior to the birth of their child (35.3%), pinpoint valuable resources and interventions (38.2%), and determine possible risk factors of neurodevelopmental delays to be considered after delivery (20.6%). Conclusion This study documented parental perspectives on the impact of an early SCA diagnosis and attitudes towards NIPT use for identifying those at risk for SCAs. These informative and insightful results provide personal experiences that health care providers may want to consider when providing prenatal counseling on NIPT for expectant mothers. As this analysis is the first of its kind, ascertainment is limited, and future research should aim to expand these findings by investigating the different factors influencing attitudes towards NIPT.

Abstract47,XXY (Klinefelter syndrome [KS]) is the most common sex chromosomal aneuploidy (1:660), yet, despite this, only 25% of the males are ever diagnosed. Males with 47,XXY present with characteristic symptoms throughout their lifetime with typical physical and neurodevelopmental manifestations focused in growth, cognitive development, endocrine function, and reproduction. Studies have demonstrated that optimal outcomes are dependent on early detection combined with consistent and targeted neurodevelopmental treatment throughout the lifespan. During infancy and into the preschool years, individuals with 47,XXY commonly face deficits in growth and development in the areas of early hormonal, motor, speech, and behavioral development. As they transition into school, the primary neurodevelopmental concerns include language difficulty, executive dysfunction, behavior, and learning and reading deficits. Adults with 47,XXY often present with taller than average height, low levels of fertility, azoospermia, and elevated gonadotropin levels. These presentations may persist from early childhood through adulthood but can be mitigated by appropriate interventions. Early neurodevelopmental and hormonal treatment has been shown to have a minimizing effect on the physical and neurodevelopmental manifestations in individuals with 47,XXY. With innovative and current research studies, the features common to the neurodevelopmental profile of 47,XXY have been further expanded and defined. Further research is necessary to elucidate and understand the relationship between the brain, behavior, and the phenotypic profile of 47,XXY.

This cross‐sectional study examined the neurodevelopment of a large, prenatally diagnosed population of boys with 47,XXY; investigated the potentially positive effects of early hormonal therapy (EHT) on language, cognition, and motor in this population; and identified novel at risk biomarkers associated with 47,XXY. Two‐hundred and seventy two evaluations were collected from 148 prenatally diagnosed boys with 47,XXY between 0 and 36 months and separated into one of three groups, depending on visit age: Y1 (0–12 months; n = 100), Y2 (13–24 months; n = 90), and Y3 (25–36 months; n = 82). Those who received EHT (administered by 12 months) were further separated (Y1, n = 37; Y2, n = 34; Y3, n = 30). Neurodevelopmental evaluations consisted of Preschool Language Scales, Early Language Milestone Scale, and Bayley Scales of Infant and Toddler Development and evaluated the effect of EHT on auditory comprehension, expressive communication, receptive language, cognition, and motor. EHT was found to be associated with a positive effect within the first year of life in these domains, as well as in the second and third year of life. Additionally, three novel at‐risk biomarkers were identified in this cohort: feeding difficulties in infancy, positional torticollis, and the need for orthotics. The positive effects of EHT observed in language, cognition, and motor at variable stages within the first 3 years of life provide additional evidence into the possible efficacy of early biological treatment for boys with 47,XXY to address the neurodevelopmental dysfunction.

49,XXXXY is the rarest X and Y chromosomal variation, with an incidence of 1 in 80,000-100,000 live male births and has been associated with numerous musculoskeletal abnormalities. Data was collected from an international cohort of boys with 49,XXXXY over 10 years. Children were evaluated by a multidisciplinary team consisting of a pediatric orthopedist, a neurogeneticist, a neurodevelopmentalist, and two physical therapists. Increased rates of torticollis (32.4%), hamstring tightness (42%), radioulnar synostosis (67.6%), pes planus (65.2%), and other foot abnormalities (86.9%) were observed. Several anomalies increased with age, specifically hamstring tightness, kyphosis, and scoliosis. The elucidation of the orthopedic profile of this population is necessary in order to provide healthcare providers with current medical information. This research further supports the necessity for the comprehensive multidisciplinary treatment of boys with 49,XXXXY.

(Abstracted from Am J Med Genet 2020;182A:1881–1889) 47,XXY (Klinefelter syndrome) is characterized by disruption in neurodevelopment, the endocrine and musculoskeletal systems, and brain morphology. It is also associated with an increased risk of asthma, infertility, decreased muscle tone, emotional lability, and decreased libido.