Case report of rare 3q27.1 microdeletion syndrome for patient with dysmorphic features, growth retardation and mild developmental delay

Abstract

Background/Objectives: Constitutional rearrangements involving chromosome 3q are very rare and overlapping microdeletions of chromosome 3q26-3q28 have only been reported in ten individuals with severe prenatal and postnatal growth restriction and neurodevelopmental abnormalities. Methods: The proband is 2-year-old female who was born at 38 weeks of gestation, birth weight 2060 g (-2.88 SD). Severe Intrauterine growth restriction was noticed from the begging of 3rd trimester. She failured to thrive during infancy with normal motor development. At the clinical visit her height was 79 cm (-2.44 SD), weight 8 kg (-4.26 SD). The hormonal assessment was performed and normal levels of IGF-1, TSH, FT4, basal cortisol levels were detected. Dysmorphic facial features were noticed: hyperthelorism, high anterior hairline, frontal bossing, depressed nasal bridge, short nose with anteverted nares, low set ears. Developmental delay was assed by scale of Diagnostic inventory for screening children, 1984 (DISC). Test value was 50-77%, especially language delay with feeding difficulties. Results: Whole Genome NGS-based Large Copy Number Variation Analysis (Centogene, Germany) was performed and 867 kb one copy loss within chromosome region 3q27.1 was detected. The deletion covered 21 genes and 9 of them were OMIMassociated with disease, particularly DVL3, AP2M1 and PARL genes. Frameshift variants in DVL3 gene are associated with autosomal dominant type III Robinow syndrome (MIM#: 616894). AP2M1 (MIM#: 601024) has role in poor speech, developmental delay, hypotonia and seizures. PARL (MIM#: 607858) possibly associated with growth restriction. Conclusion: We suggest that haploinsufficiency of DVL3, AP2M1 and PARL genes can cause 3q27.1 microdeletion phenotype.