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Joana Catanho1; Inês Carvalho1

1 - Department of Medical Genetics, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal.

- ACMG Annual Clinical Genetics Meeting 2022 (Poster) 

Background: Partial monosomy of the short arm (p) of chromosome 7 is a rare chromosomal disorder associated with a variable phenotype, depending on the size and location of the deleted region. When the deletion involves the interstitial deletion of 7p22.1p21.2 region, literature review describes phenotypic features that include craniosynostosis, microcephaly, ocular hypotelorism or hypertelorism, downslanting palpebral fissures, epicanthal folds, dysplastic ears, depressed nasal bridge, and cleft palate. Abnormalities of the thumbs and feet have been described, and also cardiovascular, renal and genital anomalies. The 7p22.1 chromosomal region encompasses, among others, the ACTB gene. Deletion of this region presents overlapping features as previously described and is associated with Baraitser-Winter syndrome (BRWS, OMIM 243310). Haploinsufficiency of ACTB has been recently suggested as a probable disease mechanism explaining the clinical phenotype observed in patients with 7p22.1 deletion.
Case presentation: We report a 1-year-old girl with healthy nonconsanguineous parents, born prematurely at 33 weeks of gestation, by elective cesarean section due to pre-eclampsia. First trimester combined screening revealed high risk for trisomy 18 (1:4), trisomy 13 (1:10) and trisomy 21 (1:127), but parents refused invasive testing. Ultrasound performed at 28 weeks and 3 days of gestation showed abnormality of the cavum septum pellucidum, omphalocele with hyperechogenic bowel, hepatomegaly, right wrist angulation, hand digits malformation, and duplex left kidney. Neonatal period was complicated due to bradycardia and low Apgar score (4, 6 and 6 at 1, 5 and 10 minutes respectively), needing intubation, ventilation, resuscitation, and epinephrine. Weight at birth was 1100 g (3rd percentile), height was 35.7 cm (3rd percentile) and occipitofrontal circumference of 26 cm. She was admitted in the Neonatal Intensive Care Unit, with the following diagnosis: prematurity, very low birth weight, polymalformative syndrome including cardiovascular, renal and neurological alterations, peri-natal hypoxia, hyaline membrane disease thrombocytopenia and hypothyroidism.  She was first observed in our Genetics Clinic at 3 months old, presenting with dolichocephaly, hypotelorism, dense eyelashes, broad nasal bridge, thin upper lip vermilion, short arms and bilateral nonfunctional thumb hypoplasia. Patient also presented with umbilical hernia, hypertonia and psychomotor development delay. Karyotype and chromosomal microarray analysis identified an 8.96 Mb heterozygous deletion involving the interstitial chromosome region 7p22.1p21.2. Parental testing revealed normal results, establishing the diagnosis of a de novo 7p22.1p21.2 microdeletion.
Conclusions: Interstitial deletion of chromosome 7p22.1p21.2 is a rare chromosomal disorder, and review for recent literature found few descriptions for this disorder.  This report highlights the importance of distinguishing prematurity complications from syndromatic features associated with a genetic syndrome.  Also, it brings to attention the importance of chromosomal microarray analysis as a molecular genetic tool that is effective to detect copy number variations and determine its breakpoints. The molecular diagnosis allowed suitable genetic counseling, facilitated informed decision-making and provided for a proper prognostic assessment. 

Palavras Chave: Microdeletion, Microarray, 7p22.1p21.2 deletion, Baraitser-Winter syndrome