Partial monosomy of chromosome 21 and congenital malformations monosomy of chromosome 21 and malformations : Clinical Dysmorphology

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Partial monosomy of chromosome 21 and congenital malformations monosomy of chromosome 21 and malformations

Osiak, Lucasa; Saraiva, João G.a; Mestre, Viviane de F.a; Ferrari, Lígia S.L.b; Paiva, Wagner J.M.c; de Lima, Renata L.L.F.d; Salles, Maria J.S.a

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doi: 10.1097/MCD.0000000000000310
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Monosomy of chromosome 21 is a rare chromosomal abnormality, which can occur as complete monosomy, mosaicism and through translocations (Toral-Lopez et al., 2012). Partial deletion of chromosome 21 has been associated with dysmorphic characteristics, cardiac defects, seizures, impaired motor function, cognitive deficit, microcephaly, epilepsy, and respiratory distress (Roberson et al., 2011; Riegel et al., 2005).

This correspondence describes a female patient, with monosomy of chromosome 21 with mosaicism, and whose parents are not blood-related and did not present alterations in their karyotype. The patient was born at the 34th week of gestation, by a Cesarean section indicated due to maternal protein S deficiency. At the prenatal stage, ultrasound examinations showed a polycystic kidney and intrauterine growth restriction. During pregnancy, the mother was 35 years old and presented a history of hypothyroidism and three idiopathic miscarriages. At birth, the neonate presented: weight of 1120 g, length 37 cm, and cephalic circumference 26.5 cm (Z score below three to the three measures). The syndromic characteristics were: low ear implantation, left ear not detached, right ear protruding, asymmetrical and pointed ears, palpebral fissures inclined downwards, long eyelashes, cranium deformities, especially in the left parietal, right mammary artery higher than the left, and deformity in the left foot with overlap of the fifth toe in relation to the fourth toe, in addition to intrauterine growth restriction. The karyotype was performed by giemsa tripsin giemsa staining, followed by analysis through CGH-Array/FISH, and showed the result: 46,XX,−21,+mar[14]/45,XX, −21 [6], being that 70% of the analyzed metaphases had monosomy 21 and one marker chromosome, and 30% of the metaphases analyzed presented complete monosomy 21. Comparative analysis by CGH detected that the distal deletion on chromosome 21 is of approximately 11.5 Mb, and affected the band 21q22.12-q.22.3 (Fig. 1). This patient also presented respiratory distress syndrome, a dysfunctional and multicystic right kidney, cardiac malformations, tetralogy of Fallot and tricuspid atresia and laryngotracheomalacia in the first year of life and feeding difficulties, what required a gastrostomy. In May 2017, she was aged 4 years and 7 months, and presented: weight 10 320 g, height 92 cm and BMI 12.2 (Z score below three to the three measures) and has been hospitalized several times with respiratory and urinary tract infections and seizures. She does not move alone and cannot pronounce words, but understands instructions.

Fig. 1:
Result of the CGH-array/FISH of the patient B.N.P. The examination showed that of the cell line with partial monosomy, which in the karyotype had been characterized as a marker chromosome, had a distal deletion of approximately 11.5Mb, affecting the region 21q22.12-q.22.3.

Some studies have shown that haploinsufficiency of the DYRK1A gene leads to intellectual impairment, primary microcephaly, intrauterine growth retardation, facial dimorphisms, impaired motor functions, including feeding difficulties during childhood, and seizures (van Bon et al., 2011; Courcet et al., 2012). B.N.P. presents deletion of the region corresponding to the DYRK1A gene in 30% of the analyzed metaphases, justifying her microcephaly, intellectual deficiency, and seizures. The patient presented cardiac malformations, which may be associated with KCNE1, RCAN1, CLIC6, and RUNX1 (Lindstrand et al., 2010), found in the region of 21q22.11-q22.12 of 2.9 Mb, deletions of which region may be seen in association with cardiac malformations in severe cardiac malformations. This region is contained in the 30% of cells that showed complete deletion of our patient’s chromosome 21.

No case reported presented laryngotracheomalacia before in the literature. In addition, no chromosome 21 gene was associated with renal alterations. It was concluded that survival was associated with the presence of mosaicism with the cell line presenting partial deletion.


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