Mosaic trisomy 4: Long-term outcome on the first reported liveborn

Abstract

In a previous report, we described the first liveborn with trisomy 4 mosaicism [Marion et al. (1990) Am J Med Genet 37:362-365]. To our knowledge, since our original report, there have been only four additional reports of a prenatal diagnosis of mosaic trisomy 4 resulting in a liveborn child [Hsu et al. (1997) Prenat Diag 17:201-242; Kuchinka et al. (2001) Prenat Diag 21:36-39; Wieczorek et al. (2003) Prenat Diag 23:128-133; Zaslav et al. (2000) Am J Med Genet 95:381-384]. Three of the more recent reports lacked confirmation of the mosaicism in tissue samples collected from the child after delivery, and likely represent cases of confined placental mosaicism. We recently examined our original patient, N.J., in an effort to provide long-term follow-up. N.J. is currently 14-years-old, and is enrolled in both special education and mainstream eighth grade classes at a local public middle school. Although she generally scores below average on standardized intellectual tests, her verbal skills and social interactions are more age appropriate. Our initial report described abnormalities of N.J.'s right hand and right ear, for which several reconstructive surgeries have been performed. A current medical concern is her entrance into puberty, as menarche has not yet occurred, and asymmetrical breast development is present. Overall, N.J. has developed into a generally healthy adolescent with low-normal intellect. This report demonstrates the importance of long-term follow-up in providing accurate counseling for rare chromosomal disorders.

A live‐born child with a mosaic chromosomal pattern of either monosomy 21 or trisomy 4 in different embryonal germ layers

“…In our patient, the evident low-set dysplastic ears, holoprosencephaly, lung hypoplasia, cystic renal dysplasia, and abnormalities of hands and feet have been previously reported in the literature (Marion et al, 1990;Mori et al, 2004;Brady et al, 2005;Nguyen et al, 2009) in cases with monosomy 21 or in cases with trisomy 4. Mandibular agenesis has not previously been correlated to either one of the chromosomal abnormalities.…”

“…None of the tissues examined show both chromosomal abnormalities. We cannot exclude the fact that some of the tissues might have been Trisomy 4 mosaicism is very rare in live-borns, and only five patients have been described (Marion et al, 1990;Zaslav et al, 2000;Kuchinka et al, 2001;Wieczorek et al, 2003;Brady et al, 2005). Although the number of patients is small clinical findings consist of reduced birth weight and length, microcephaly, minor facial dysmorphisms, short neck, unilateral absence of thumb, hypoplastic distal phalanges, and congenital heart defects [ventral septal defect (VSD)].…”

Linear and whorled naevoid hypermelanosis in a patient with trisomy 4 mosaicism

“…Mosaic trisomy 4 is very rare, and occurs when only some of the body's cells have an extra copy of chromosome 4. The signs and symptoms vary widely, and can include unusual facial appearance, developmental delay, heart defects, abnormalities of the fingers and toes, anal atresia, and other birth defects . Underlying chromosomal mosaicism and cytogenetic changes have been observed in only some individuals with LWNH.…”

“…The signs and symptoms vary widely, and can include unusual facial appearance, developmental delay, heart ª 2014 British Association of Dermatologists defects, abnormalities of the fingers and toes, anal atresia, and other birth defects. 7 Underlying chromosomal mosaicism and cytogenetic changes have been observed in only some individuals with LWNH. However, false-negative results cannot be excluded if cytogenetic studies are performed only on peripheral blood.…”

Implications of fetoplacental mosaicism on cell‐free DNA testing: a review of a common biological phenomenon

“…In the second situation (CPM Types 1 and 3), the only rare mosaic trisomies in CV showing a likelihood of fetal confirmation are the mosaic trisomies 4 (T4) and 16 (T16). Clinical consequences of a fetal mosaic T16 or T4 are unpredictable and largely dependent on the mosaicism level in the fetus. As for ‘large’ partial CNVs, and even for rare full chromosomal trisomies, their presence in fetal tissue in a consistent level of mosaicism would trigger fetal ultrasound abnormalities or a lethal phenotype.…”