Segregation of a paternal insertional translocation results in partial 4q monosomy or 4q trisomy in two siblings

Abstract

A genetics evaluation was requested for a 6‐week‐old infant with multiple congenital malformations including mild craniofacial anomalies, truncal hypotonia, hypospadias, and a ventriculoseptal defect. Blood obtained for chromosome analysis revealed an abnormal chromosome 4. Paternal chromosome analysis showed a 46,XY, inv ins (3;4) (p21.32; q25q21.2), inv(4)(p15.3q21.2) karyotype. Therefore, the proband's chromosome 4 was the unbalanced product of this insertional translocation from the father resulting in partial monosomy 4q. Additionally, the derivative 4 had a pericentric inversion which was also seen in the father's chromosome 4. During genetic counseling, the proband's 2‐year‐old brother was evaluated. He was not felt to be abnormal in appearance, but was described as having impulsive behavior. Chromosome analysis on this child revealed 46,XY,der(3)inv ins(3;4)(p21.32;q25q21.2)pat. This karyotype results in partial trisomy 4q. FISH using two‐color “painting” probes for chromosomes 3 and 4 confirmed the G‐banded interpretation in this family. The segregation seen in this family resulted in both reciprocal products being observed in the two children, with partial 4q monosomy showing multiple congenital anomalies, and partial 4q trisomy showing very few phenotypic abnormalities. © 1995 Wiley‐Liss, Inc.

De novo interstitial duplication 4(q28.1q35) associated with choanal atresia

“…The only problem was impulsive behaviour. 11 Renal and thumb anomalies were noted in nine cases of dup4q reviewed by Zollino et al ., three of which were of pure partial trisomy 4q, 4,8,9 all of them having breakpoints spanning over 4q22-q23. Zollino et al .…”

“…However, normal intelligence was also reported in a case of dup 4q(21.2‐q25) in a 3.25‐year‐old boy, resulting from malsegregation of a paternal insertional translocation, and without apparent dysmorphic features. The only problem was impulsive behaviour 11 .…”

“…Pure trisomy 4q has been reported in a limited number of cases. Through a literature search, we have identified 13 reports of pure partial trisomy 4q, arising either from a simple duplication, [1][2][3][4][5][6][7][8][9] parental insertion, 10,11 or from acrocentric translocation. 12,13 Clinical features of our case are compared with reported pure partial trisomy 4q cases in the literature (Table 1).…”

Molecular and clinical characterization of a patient with duplication of 1p36.3 and metopic synostosis

“…The authors suggest a possible dosage effect for FGFR3, causing the different growth expression in these two phenotypes. Another example of striking differences in deletion versus duplication of a chromosomal region is seen in a family with a paternal insertional translocation involving chromosome 4q21 to q25 and the observation of the reciprocal products in two of his offspring [24]. One son had congenital heart disease, hypospadias, abnormal facial features, and global developmental delay.…”

Duplicación parcial del cromosoma 4 asociada con coloboma ocular bilateral

“…12 Elghezal y cols., publicaron acerca de otro niño sano con una duplicación aún más larga (4q25-q34), cuya única manifestación fenotípica fue un leve retraso mental asociado a un déficit del lenguaje. 13 En el análisis comparativo realizado por estos últimos autores se sugiere que la región 4q31-q33 podría estar involucrada en el desarrollo de las características dismórficas típicas de esta duplicación, mientras que la banda distal 4q35 podría asociarse con el desarrollo de microcefalia, retraso mental grave y retraso de crecimiento.…”