Mosaic proximal trisomy 13q and regular trisomy 13 in a female patient with long survival: Involvement of an incomplete trisomic rescue and a chromothripsis event

Abstract

Background Trisomy 13 or Patau syndrome has a prevalence of 1:10,000–20,000 and is characterized by microcephaly, microphthalmia, polydactyly, as well as other dysmorphic features and malformations, with a patient survival of 13% in the first year. Trisomy 13 presents either as a free chromosome 13 trisomy or associated with a chromosomal Robertsonian translocation, as partial trisomy affecting proximal or distal 13q regions, and also as a mosaic. Mosaic trisomy 13 shows a highly variable phenotype, displaying from mild to severe affectations. We present a 12‐year‐old Mexican female patient with intellectual disability, dysmorphic features, polymenorrhea, and long survival, whose initial cytogenetic study referred to a small supernumerary marker chromosome. Methods GTG banding karyotype, high‐resolution chromosomal microarray, and fluorescent in situ hybridization analyses were performed in peripheral blood cells. Results Our analyses demonstrated a de novo mosaicism in our patient, constituted by proximal trisomy 13q10‐q14.3 (82%) and free trisomy 13 (18%) cell lines. Her final chromosomal complement is mos 47,XX,+del(13)(q14.3)[25]/47,XX,+13[7].ish del(13)(RB1+)[17]/13q14(RB1x3)[2].arr[GRCh37] 13q11q14.3(19436286_51726415)x3,13q11q34(19436286_115107733)x2‐3 dn. Conclusions The wide spectrum of clinical manifestations observed in our patient mainly results from the proximal trisomy 13q, and her phenotype is modified by the presence of a free trisomy 13 cell line. We propose that her mosaicism probably derived from a trisomic zygote that underwent a failed trisomic rescue associated with chromothripsis, originating the cell line with partial 13q proximal trisomy, whose selective advantage could explain the long survival of our patient.

A Six-Year-Old Child With Mosaic Trisomy 13

“…They reported that she could support her head and sit at eight months, could stand at one year and two months, and walk without help at two years of age. At the age of 12 years, she can say few monosyllabic words without an appropriate context [2]. In our case, the child was able to hold his head at two months, sit at seven months, and at the age of one year, he was able to stand and cruise around furniture by himself.…”

“…At the age of six years, he can say two to three words phrases and knows numbers and colors. Morán-Barroso et al reported that pigmentary anomalies, like hyperpigmented and hypopigmented skin lesions, are present in 82% of patients with mosaic trisomy 13 [2]. No pigmentations or any type of skin lesions are present in the reported patient.…”

“…Survival after the first year is rare, and there are few other reported cases that survived beyond 10 years [1]. Trisomy 13 is associated with central nervous system malformations like holoprosencephaly, congenital heart defects like atrial-septal defect and ventricular-septal defect, psychomotor delay, and mental retardation [2]. Early death is mainly attributed to central nervous system and cardiac anomalies [3].…”

Moyamoya syndrome secondary to mitochondrial disease in a patient with partial trisomy 13q14 and 13q31: A novel case report and literature review

“…Trisomy 13, or Patau Syndrome, is a chromosomal aberration that results in an extra duplicate of chromosome 13 being present in the body cells. Trisomy 13 may be full trisomy 13 (a third copy of chromosome 13 exists in all cells), mosaic trisomy 13 (a third copy of chromosome 13 exists only in some cells), or partial trisomy 13 (only a partial third copy of chromosome 13 exists in all cells) [ 22 , 23 ]. Partial trisomy is typically only of the 13q type, meaning the extra copy present is that of the long arm (q) of chromosome 13 [ 23 ].…”

“…Trisomy 13 may be full trisomy 13 (a third copy of chromosome 13 exists in all cells), mosaic trisomy 13 (a third copy of chromosome 13 exists only in some cells), or partial trisomy 13 (only a partial third copy of chromosome 13 exists in all cells) [ 22 , 23 ]. Partial trisomy is typically only of the 13q type, meaning the extra copy present is that of the long arm (q) of chromosome 13 [ 23 ]. Furthermore, partial trisomy 13q is characterized by the presence of distinct symptoms including microcephaly, holoprosencephaly, leukoencephalopathy, facial anomalies, and intellectual disability [ 24 , 25 ].…”