*Correspondence: renata.rao@hotmail.com.
Abstract
Case Presentation: An 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.
Discussion: 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.
Final Comments: 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.
