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Título

AN ULTRARARE CHROMOSOMAL ABERRATION COMPATIBLE WITH LIFE: 49 XXXXY SYNDROME

Apresentação do caso único

Case report: Boy, 1 year and 5 months old, only child of non-consanguineous parents, mother 30 years old, Father 35 years old, pregnancy without complications, normal delivery, at term, low weight, evolved with weak suction and hearing deficit on the right. Neuropsychomotor developmental delay (DD) was observed at 3 months, cephalic control at 6 months, sitting with support at 8 months, not walking or speaking. He evolved with a slowdown in weight and height gain, bilateral cryptorchidism and micropenis. Currently, he has fleeting visual support, low social interaction, hand and head stereotypes, irritability and delayed tooth eruption; low weight and height for his age; dysmorphic features such as bilateral single palmar line, overlapping of the 2nd and 5th fingers, short toes and eversion of the feet, convergent strabismus and weak crying, axial hypotonia and mild hypertonia of the lower limbs, distal hypotrophy, global muscle strength grade IV/V. Echocardiogram: ventricular septal defect. Brain MRI: hyposignal on T1 and hypersignal on FLAIR and T2 in the supratentorial white matter, more evident in the posterior periventricular regions, moderate ectasia of the supratentorial ventricular system, diffuse thinning of the corpus callosum. Exome: extranumerous X chromosomes; SNP array: three additional X chromosomes, compatible with karyotype 49, XXXXY, considered pathogenic.

Discussão

Discussion: 49,XXXXY syndrome is an extremely rare aneuploidy of the sexual chromosomes, with an estimated incidence of 1:85,000 to 1:100,000 live male births. It is characterized by intellectual, motor and language deficiencies, dysmorphisms, cardiac, endocrinological, bone and/or renal alterations. This syndrome is caused by double non-disjunction of homologous chromosomes or sister chromatids during maternal phases meiosis I and II, resulting in three additional X chromosomes. Well-established risk factors have not been identified. Diagnosis is made by tests that assess the number of copies, such as karyotype or SNP array. Treatment is multi-professional and supportive.

Comentários finais

Final considerations: 49,XXXXY syndrome is a complex genetic disorder, considered a more severe variant of Klinefelter syndrome (47,XXY), mainly affecting neurodevelopment. With the advances in genetic tests, in patients with non-specific dysmorphims associated with DD, the Exome can be a first-line test, and when necessary, diagnostic confirmation complemented by other tests, as in this case, by the microarray.

Referências

Gropman, Andrea L et al. “Neurocognitive development and capabilities in boys with 49,XXXXY syndrome.” American journal of medical genetics. Part A vol. 185,12 (2021): 3541-3546.
Frühmesser, A, and D Kotzot. “Chromosomal variants in klinefelter syndrome.” Sexual development: genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation vol. 5,3 (2011): 109-23.
Samango-Sprouse, Carole et al. “49,XXXXY syndrome: A study of neurological function in this uncommon X and Y chromosomal disorder.” American journal of medical genetics. Part A vol. 185,12 (2021): 3557-3566.

Palavras Chave

49 XXXXY SYNDROME; ULTRARARE; CHROMOSOMAL ABERRATION