An Exploration of the Neurodevelopmental Phenotype of Five Patients with 48,XXYY during Early Childhood Years

Margaret Olaya¹Carole Samango-Sprouse^1,2,3*Debra Counts⁴Antonie Kline⁵Francie Mitchell¹Elizabeth Buscema¹Elizabeth Tipton¹Teresa Sadeghin¹Andrea Gropman^4,6

• ¹The Focus Foundation, Crofton, United States
• ²George Washington University, Washington, D.C., United States
• ³Florida International University, Miami, United States
• ⁴Sinai Hospital, Baltimore, United States
• ⁵Greater Baltimore Medical Center Harvey Institute for Human Genetics, Baltimore, United States
• ⁶St Jude Children's Research Hospital, Memphis, United States

Background 48,XXYY is a sex chromosome aneuploidy (SCA) occurring in 1:18,000-50,000 male births characterized by androgen deficiency in conjunction with hypogonadism, hypertelorism, clinodactyly, pes planus, radioulnar synostosis, increased height velocity, hypotonia, and a suspected increased incidence of autism spectrum disorder (ASD). The neurodevelopmental phenotype includes motor dysfunction, speech/language disturbance, and intellectual deficits. Aim This series will compare the neurodevelopmental profile of five patients with 48,XXYY during early childhood. Methods Five cases of males with 48,XXYY were followed beginning at the time of diagnosis. Each case underwent a combination of neurodevelopmental, oral motor, speech/ language, physical therapy, medical genetics, and/or neurology evaluations. Results In the five cases presented there was an increased incidence of torticollis with the right side more common. Abnormal muscle tonus was noted in all cases, characterized by truncal, upper extremities, and oral motor musculature hypotonia. Four of the patients exhibited an increased head circumference (≥ 79th percentile) by 7 months of age. All cases had speech/language and motor delays evident in the first 12 months of life and no signs of ASD prior to 3 years of age. Conclusions The presentation of 48,XXYY is varied, including oral motor deficits, hypotonia, positional and congenital muscular torticollis, respiratory issues, and inner-ear dysfunction. Early presentations of infantile developmental dyspraxia are evident by 18-months-old; specifically, discrepancies between fine and gross motor and expressive and receptive language skills. This series provides additional aspects to the phenotypic presentation of males with 48,XXYY during infancy and early childhood as well as identifies common complications.