18º Congresso Brasileiro de Neurologia Infantil

Dados do Trabalho



Apresentação do caso

8 years-old boy, with no gestational or perinatal complications,
presenting developmental delay, nystagmus, facial dysmorphia, hypotonia, hypotonia, joint
hypermobility, patellar luxation, cryptorchidism and hypothyroidism. The genome sequencing
revealed a likely pathogenic variant c.3842_3843del:p. (Val1281Alafs*22) in the KAT6B
gene, in heterozygosis, associated to Say-Barber-Biesecker-Young-Simpson Syndrome and
Genitopatellar Syndrome, both with autosomal dominant inheritance pattern.
Girl, 16 years old, paternal cousin of the firt case, presenting consanguinity (first cousin
parents ​​with paternal and maternal grandparents monozygotic twin brothers) with no
gestational or perinatal complications presenting developmental delay, nystagmus, facials
dysmorphias, hypotonia, low visual acuity, ataxic gait, alopecia, finger syndactyly and
patellar luxation. In the genome was found a pathogenic variant c.830del:p
(Gly277AlafsTer20), residing in the CDH3 gene, in homozygosity; and another probably
pathogenic variant c.3379A>T:p.(Lys1127Ter) in the PRX gene, in homozygosity. The CHD3
gene is associated with the phenotypes of Ectodermal Dysplasia, Ectrodactyly and Macular
Dystrophy (DEEDM) and Congenital Hypertrichosis with Juvenile Macular Dystrophy
(HCDM), both with recessive autosomal inheritance; while the PRX gene is related with the
phenotypes of Charcot-Marie-Tooth Disease 4F type, of autosomal recessive inheritance,
and of Dejerine-Sottas Disease of autosomal dominant or recessive inheritance.


Diseases associated with the genes reported in the diagnostic analysis of
these cousins ​​are rare, with an estimated global prevalence of <1/1,000,000. The increase in
the frequency of autosomal recessive diseases caused by consanguinity is due to the finding
of rare variants in alleles inherited from a common ancestor. The identification in
homozygosis, in two genes reinforce the parental relationship of parents. In the grisl’s case it
can be observed that the characteristics of the complex phenotype correspond to alterations
in two distinct genes. However, characteristics often shared by members of the same family
need to be better investigated by molecular genetic tests.

Comentários finais

The described individuals, despite sharing important family consanguinity,
as well as some phenotypic characteristics suggesting involvement of one or more genes
segregating in the family, have distinct molecular diagnosis.

Referências (se houver)

Clayton-Smith J et al. Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome. Am J Hum Genet. 2011 Nov 11;89(5):675-81. doi: 10.1016/j.ajhg.2011.10.008. PMID: 22077973; PMCID: PMC3213399.
Lemire G, Campeau PM, Lee BH. KAT6B Disorders. 2012 Dec 13 [Updated 2020 Jan 2]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK114806/.
Zhang LX et al. Further delineation of the clinical spectrum of KAT6B disorders and allelic series of pathogenic variants. Genet Med. 2020 Aug;22(8):1338-1347. doi: 10.1038/s41436-020-0811-8. Epub 2020 May 19. PMID: 32424177; PMCID: PMC7737399.
Radvanszky J et al. Complex phenotypes blur conventional borders between Say-Barber-Biesecker-Young-Simpson syndrome and genitopatellar syndrome. Clin Genet. 2017 Feb;91(2):339-343. doi: 10.1111/cge.12840. Epub 2016 Sep 29. PMID: 27452416.
Lundsgaard M et al. De novo KAT6B Mutation Identified with Whole-Exome Sequencing in a Girl with Say-Barber/Biesecker/Young-Simpson Syndrome. Mol Syndromol. 2017 Jan;8(1):24-29. doi: 10.1159/000452258. Epub 2016 Nov 5. PMID: 28232779; PMCID: PMC5260604.
Baets et al. Genetic spectrum of hereditary neuropathies with onset in the first year of life. Brain 134: 2664-2676, 2011.

Palavras Chave

SBBYSS;GTPTS;KAT6B;Genitopatellar syndrome; Say-Barber-Biesecker-Young-Simpson syndrome; Charcot-Marie-Tooth Disease; Ectodermal Dysplasia; Ectrodactyly and Macular Dystrophy

Fonte de Fomento (se houver)

Declaração de conflito de interesses de TODOS os autores





Renata Andrade Oliveira, Renata Andrade Oliveira, Emília Katiane Embiruçu de Araujo Leão, Emília Katiane Embiruçu de Araujo Leão, Vinícius Lima Ferraz, Vinícius Lima Ferraz, Jemima Araújo da Silva Batista, Jemima Araújo da Silva Batista