Clinical report of 8 patients with 49,XXXXY syndrome: Delineation of the facial gestalt and depiction of the clinical spectrum

Associated anomalies in cases with agenesis of the corpus callosum

“…Aicardi syndrome was the most common associated syndrome with 62 cases including one male, followed by Dandy–Walker syndrome, 24 cases. Over 200 genetic syndromic conditions associated with ACC are listed in the Online Mendelian Inheritance in Man (OMIM) database, including syndromes with identified genes, syndromes with ACC seen consistently, no gene yet identified, and syndromes with ACC seen occasionally (Burgemeister et al, ; Lefebvre et al, ; Palmer & Mowat, ; Paul et al, ; Platzer et al, ; Romaniello et al, ; Wojcik et al, ).…”

Behavioral phenotype of 49,XXXXY syndrome: Presence of anxiety‐related symptoms and intact social awareness

“…Gropman et al, evaluated seven boys with 49,XXXXY using the Gilliam Autism Rating Scale (GARS‐2) and found that none were at risk for being on the autism spectrum. Similarly, a case report of eight patients with 49,XXXXY found only one of the eight children had a diagnosis of ASD at the time of evaluation and that most of the patients were socially outgoing (Burgemeister et al, ).…”

“…In a study of 12 boys with 49,XXXXY between 5 and 17 years of age, Blumenthal et al found significantly greater problems in internalizing and externalizing behaviors as well as social, thought, and attention problems as compared to boys with 46,XY (Blumenthal et al, ). Additionally, in a case report of 8 patients, Burgemeister et al found that boys with 49,XXXXY had higher incidences of impulsivity, eloping, and verbal aggression, but not physical aggression (Burgemeister, Gronwald, Maurer, & Zirn, ). These studies have demonstrated a wide variability in behaviors in 49,XXXXY, with some boys having low to no reported behavioral concerns to others with more severe behavioral problems including inappropriate language, tantrums, and aggression.…”

Impact of early diagnosis and noninvasive prenatal testing (NIPT): Knowledge, attitudes, and experiences of parents of children with sex chromosome aneuploidies (SCAs)

“…48,XXXY has an incidence of one in 40 000 to 60 000, while 49,XXXXY is the least common SCA, with an incidence of one in every 100 000 births. Both disorders include mild to severe dysmorphology, childhood apraxia of speech, and musculoskeletal problems that become more prevalent with age . Although the neurodevelopmental profiles of SCAs with multiple additive chromosomes are quite complicated, previous studies indicate the benefits to early detection and intervention for these populations …”

“…Both disorders include mild to severe dysmorphology, childhood apraxia of speech, and musculoskeletal problems that become more prevalent with age. 8,25,[28][29][30] Although the neurodevelopmental profiles of SCAs with multiple additive chromosomes are quite complicated, previous studies indicate the benefits to early detection and intervention for these populations. 23,28,31 Over 50 years of publications have demonstrated significant evidence to the importance of early identification of SCAs and the positive impact of early intervention on neurodevelopmental outcomes.…”