Dados do Trabalho

Título

Syndromic Intellectual Disability AD 29: Case Report

Apresentação dos casos

This is a 12-year-old female adolescent with onset global neuro psychomotor developmental delay, significant verbal communication impairment with dysarthria and dyslalia, agitation, impulsivity, dysmorphisms (thin arched eyebrows, tubular nose, relevant microretrognathia, protrusion of upper incisors, clinodactyly of fifth finger). The neuropsychological assessment showed an Intellectual Quotient (IQ) of 59 and sublevels of attention and hyperactivity incompatible with mental age and suggested a diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) as a comorbidity. Array testing showed arr[GRCh38] 18q12.3q21.1(44704004_46650765)x1, which results in haploinsufficiency of the SETBP1 gene and characterizes Autosomal Dominant Intellectual Disability 29 (DI AD 29). Magnetic resonance imaging of the brain revealed no structural alterations and the electroencephalogram showed no changes. The patient showed a good response to the use of psychostimulants, with longitudinal gains in autonomy and lifestyle habits.

Discussão

The etiologic diagnosis of ID is a challenge because it is a multifactorial condition, related to genetic or environmental causes or both. Trio exome is the most effective complementary test for identifying the culprit of ID of genetic etiology, with up to 50% success rate in the cases tested, while array analysis approaches a success rate of close to 20%. In situations where there is a recognizable phenotype, the investigation should include specific molecular tests related to the clinical presentations. In the case described, the etiology of ID by array was sufficient and provided individualization of clinical management, such as characterization of speech and language disorder, specific management of ADHD and epilepsy surveillance.

Comentários finais

The importance of the etiological definition of syndromic ID lies in the prognosis and clinical management of each condition. In our case, syndromic ID AD 29 is related to SETBP1 Haploinsufficiency Disorder and the recognition of associated comorbidities, such as ADHD, was crucial to establishing a specific therapy, improving daily living activities and quality of life.

Referências

1. Jansen NA, Braden RO, Srivastava S, Otness EF, Lesca G, Rossi M, Nizon M, Bernier RA, Quelin C, van Haeringen A, Kleefstra T, Wong MMK, Whalen S, Fisher SE, Morgan AT, van Bon BW. Clinical delineation of SETBP1 haploinsufficiency disorder. Eur J Hum Genet. 2021 Aug;29(8):1198-1205. doi: 10.1038/s41431-021-00888-9. Epub 2021 Apr 19. PMID: 33867525; PMCID: PMC8385049.
2. Morgan A, Braden R, Wong MMK, Colin E, Amor D, Liégeois F, Srivastava S, Vogel A, Bizaoui V, Ranguin K, Fisher SE, van Bon BW. Speech and language deficits are central to SETBP1 haploinsufficiency disorder. Eur J Hum Genet. 2021 Aug;29(8):1216-1225. doi: 10.1038/s41431-021-00894-x. Epub 2021 Apr 27. PMID: 33907317; PMCID: PMC8384874.

Palavras Chave

intellectual disability; Genetics Behavioral; Genetic Research