16p11.2 deletion syndrome

Rare condition caused by a microdeletion on the short arm of chromosome 16 December 2023 2 16p11.2 deletion syndrome motor speech and developmental coordination disorders, language disorder, psychiatric conditions, autism spectrum features Obesity and related comorbidities Genetic testing Global developmental delay, autism spectrum disorder, any chromosome abnormality associated with intellectual disability Genetic (typically de novo) Depends on symptoms ~1 in 2,000 16p11.2 deletion syndrome is a rare genetic condition caused by microdeletion on the short arm of chromosome 16. Most affected individuals experience global developmental delay and intellectual disability, as well as childhood-onset obesity. 16p11.2 deletion is estimated to account for approximately 1% of autism spectrum disorder cases. Signs and symptoms Developmental and behavioral The most commonly observed features of 16p11.2 deletion syndrome are global developmental delay and psychiatric or behavioral issues, though severity varies significantly. Most people with the deletion don't have intellectual disability, but many have learning disabilities. The average IQ of individuals with 16p11.2 deletion syndrome is approximately 2 standard deviations below that of family members without the deletion. Many have language disorders and motor speech disorders including dysarthria and apraxia. Half of affected individuals have at least one psychiatric or behavioral diagnosis. Approximately 30% of individuals are diagnosed with attention deficit hyperactivity disorder. Approximately 20-25% of individuals are diagnosed with autism spectrum disorder (ASD), and nearly all share some behavioral traits with ASD. Neurologic Up to 25% of affected individuals experience seizures. The most common type is tonic-clonic seizure; complex focal seizures and absence seizures are also reported. Many individuals may exhibit EEG, CT, or MRI abnormalities. Hyporeflexia, gait abnormalities, and truncal or symmetric limb hypotonia were observed in at least 15% of individuals in a cohort of 136 16p11.2 deletion carriers. Sensorineural or conductive hearing loss and paroxysmal kinesigenic choreoathetosis are observed in some individuals. Obesity 16p11.2 deletion syndrome strongly predisposes individuals to increased body mass index (BMI) and obesity beginning in childhood. BMI in individuals with the syndrome is significantly higher than that in the general population by age 5, and 50% of carriers are obese by age 7. By adulthood, 75% of individuals are obese. Affected individuals report hyperphagia due to sensory and social cues or boredom. Obesity and related comorbidities such as insulin resistance or type 2 diabetes comprise the majority of medical challenges for adults with 16p11.2 deletion syndrome. Other Macrocephaly is slightly more prevalent in 16p11.2 deletion syndrome compared to the general population. Approximately one-third of individuals have a sacral dimple or café au lait spots. Vertebral anomalies associated with scoliosis are also observed. 16p11.2 deletion has been associated with a 13.9-fold increased risk of neuroblastoma. Genetics 16p11.2 deletion syndrome is caused by a heterozygous microdeletion of ~600 kilobases between the recurrent breakpoint regions BP4 and BP5 on the short arm of chromosome 16. Genes in the BP4-BP5 region include the following: 10em SLC7A5P1 SPN QPRT C16orf54 ZG16 MAZ PRRT2 C16orf53 MVP CDIPT SEZ6L2 ASPHD1 KCTD13 TMEM219 TAOK2 HIRIP3 INO80E DOC2A C16orf92 FAM57B ALDOA PPP4C TBX6 YPEL3 GDPD3 MAPK3 CORO1A BOLA2 SLX1A SLX1B SULT1A3 SULT1A4 Nearby regions on chromosome 16 may also be affected. Notably, deletion of SH2B1 is associated with obesity and may be involved in the pathogenesis of obesity observed in the syndrome. 16p11.2 deletion typically occurs by de novo mutation. Approximately 7% of affected individuals inherit the mutation from a parent in an autosomal dominant fashion. Parents carrying the deletion often have no history of intellectual disability or autism spectrum disorder. Prevalence of 16p11.2 deletion syndrome was initially estimated to be 3 in 10,000 in the general population, though more recent estimates have increased to 1 in 2,000. Management Management of 16p11.2 deletion syndrome is highly variable and based on an individual's specific symptoms or deficits. Interventions may include special education, psychiatric treatment, standard epilepsy treatment, audiology assessment, physical and occupational therapy for gross/fine motor skills, and regular monitoring of congenital anomalies or defects. Due to increased risk of obesity associated with the syndrome, psychiatric medications associated with weight gain are not recommended. Social work involvement and community support can also benefit affected individuals and caregivers. References Taylor Cora M. Smith Rebecca Lehman Christopher Mitchel Marissa W. Singer Kaitlyn Weaver W. Curtis Chung Wendy 16p11.2 Recurrent Deletion GeneReviews 1993 https://www.ncbi.nlm.nih.gov/books/NBK11167/ University of Washington, Seattle 20301775 Weiss Lauren A. Shen Yiping Korn Joshua M. Arking Dan E. Miller David T. Fossdal Ragnheidur Saemundsen Evald Stefansson Hreinn Ferreira Manuel A.R. Green Todd Platt Orah S. Ruderfer Douglas M. Walsh Christopher A. Altshuler David Chakravarti Aravinda Tanzi Rudolph E. Stefansson Kari Santangelo Susan L. Gusella James F. Sklar Pamela Wu Bai-Lin Daly Mark J. Association between Microdeletion and Microduplication at 16p11.2 and Autism New England Journal of Medicine 14 February 2008 358 7 667–675 10.1056/NEJMoa075974 free 18184952 Fetit Rana Price David J. Lawrie Stephen M. Johnstone Mandy Understanding the clinical manifestations of 16p11.2 deletion syndrome: a series of developmental case reports in children Psychiatric Genetics October 2020 30 5 136–140 10.1097/YPG.0000000000000259 32732550 7497286 0955-8829 Szelest Monika Stefaniak Martyna Ręka Gabriela Jaszczuk Ilona Lejman Monika Three case reports of patients indicating the diversity of molecular and clinical features of 16p11.2 microdeletion anomaly BMC Medical Genomics 10 March 2021 14 1 76 10.1186/s12920-021-00929-8 33691695 7945342 1755-8794 free Chung Wendy K. 12 October 2011 An Overview of Monogenic and Syndromic Obesities in Humans Pediatr Blood Cancer 58 1 122–128 10.1002/pbc.23372 21994130 3215910 1545-5009 Chung Wendy K Roberts Timothy PL Sherr Elliott H Snyder LeeAnne Green Spiro John E 16p11.2 deletion syndrome Current Opinion in Genetics & Development 1 June 2021 68 49–56 10.1016/j.gde.2021.01.011 33667823 10256135 0959-437X Zufferey Flore Sherr Elliott H Beckmann Noam D Hanson Ellen Maillard Anne M Hippolyte Loyse Macé Aurélien Ferrari Carina Kutalik Zoltán Andrieux Joris Aylward Elizabeth Barker Mandy Bernier Raphael Bouquillon Sonia Conus Philippe Delobel Bruno Faucett W Andrew Goin-Kochel Robin P Grant Ellen Harewood Louise Hunter Jill V Lebon Sébastien Ledbetter David H Martin Christa Lese Männik Katrin Martinet Danielle Mukherjee Pratik Ramocki Melissa B Spence Sarah J Steinman Kyle J Tjernagel Jennifer Spiro John E Reymond Alexandre Beckmann Jacques S Chung Wendy K Jacquemont Sébastien A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders Journal of Medical Genetics October 2012 49 10 660–668 10.1136/jmedgenet-2012-101203 free 23054248 3494011 Gill Richard Chen Qixuan D'Angelo Debra Chung Wendy K. Eating in the absence of hunger but not loss of control behaviors are associated with 16p11.2 deletions: 16p11.2 Deletion and Disinhibited Eating Obesity December 2014 22 12 2625–2631 10.1002/oby.20892 free 25234362 Steinman Kyle J. Spence Sarah J. Ramocki Melissa B. Proud Monica B. Kessler Sudha K. Marco Elysa J. Green Snyder LeeAnne D'Angelo Debra Chen Qixuan Chung Wendy K. Sherr Elliott H. 16p11.2 deletion and duplication: Characterizing neurologic phenotypes in a large clinically ascertained cohort American Journal of Medical Genetics Part A November 2016 170 11 2943–2955 10.1002/ajmg.a.37820 27410714 2469192 Egolf Laura E. Vaksman Zalman Lopez Gonzalo Rokita Jo Lynne Modi Apexa Basta Patricia V. Hakonarson Hakon Olshan Andrew F. Diskin Sharon J. Germline 16p11.2 Microdeletion Predisposes to Neuroblastoma The American Journal of Human Genetics September 2019 105 3 658–668 10.1016/j.ajhg.2019.07.020 free 31474320 6731370 Kleinendorst Lotte van den Heuvel Lieke M. Henneman Lidewij van Haelst Mieke M. Who ever heard of 16p11.2 deletion syndrome? Parents' perspectives on a susceptibility copy number variation syndrome European Journal of Human Genetics September 2020 28 9 1196–1204 10.1038/s41431-020-0644-6 32415274 7608422 en 1476-5438 External links LD44.G1 Q93.5 611913 10740 Proximal 16p11.2 microdeletion syndrome 261197 Category:Syndromes with intellectual disabilities Category:Syndromes with obesity Category:Syndromic autism Category:Autosomal monosomies and deletions Category:Autosomal dominant disorders