Refinement of the critical region in a new 7p22.1 microduplication syndrome including craniofacial dysmorphism and speech delay

7p22.1 microduplication syndrome: Clinical and molecular characterization of an adult case and review of the literature

“…He presents facial features as thick and arched eyebrows, prominent nose with bulbous tip, short philtrum and thin upper lip that are described also in patients with larger 7p pure duplications (Table 1; Papadopoulou et al, 2006). Cryptorchidism reported in the two previously described males was also present in our patient (Table 1; Chui et al, 2011;Pebrel-Richard et al, 2014). Although skeletal anomalies seem to be a common clinical finding since they are present in three out of four previously described patients (AlFardan et al, 2011;Chui et al, 2011;Preiksaitiene et al, 2012), our patient and the one described by Pebrel-Richard, do not show skeletal anomalies (Table 1).…”

“…The distal larger microduplication is the smallest reported so far, and fully encompasses the minimal region of 430 kb highlighted by PebrelRichard et al as critical of this newly described syndrome (Fig. 4; Pebrel-Richard et al, 2014;Preiksaitiene et al, 2012). The emerging phenotype of the reported patients carrying microduplications involving this region, whose age ranges from 28 months to 14 years, includes speech delay and craniofacial dysmorphisms such as macrocephaly, hypertelorism, anteverted nares and ear anomalies (Table 1; clinical features, our patient shares speech delay, with verbal IQ score of 40, a dysarthric speech and ear anomalies with bilateral underfolded helices and mildly underdeveloped tragus.…”

“…Later on only five 7p microduplications detected by array-CGH have been characterized. All of them, except for the approximately 5 Mb microduplication involving the terminal region (Zahed et al, 2007), are interstitial microduplications located in the 7p22 band (AlFardan et al, 2011;Chui et al, 2011;Pebrel-Richard et al, 2014;Preiksaitiene et al, 2012). Interestingly, the 2.4 Mb duplication spanning 7p22.1p22.2 reported in an 11 year-old female with a "classic 7p duplication phenotype" was inherited from the mother who presented only with some facial features in common with her daughter and mild cognitive disability (AlFardan et al, 2011).…”

“…Given that 7p22.1 microduplications are associated with common clinical features recorded in patients with larger duplications as well, the region indicated by Preiksaitiene et al (2012) has been proposed as critical for a 7p22.1 recognizable microduplication syndrome which hallmarks are developmental delay, distinctive facial features and skeletal anomalies. More recently, Pebrel-Richard et al has described a 3 year-old boy carrying a 7p22.2p22.1 microduplication of about 1.6 Mb who displayed psychomotor and speech delay, several craniofacial dysmorphisms typical of 7p duplication plus joint hypermobility, truncal stereotypies and attention deficit disorder (ADD) (Pebrel-Richard et al, 2014). This microduplication partially overlaps with the smallest duplicated region reported by Preiksaitiene et al (2012), allowing to highlight a minimal critical region of 430 kb encompassing five genes: TNRC18, FBXL18, ACTB, FSCN1 and RNF216.…”

Multiple copy number variants in a pediatric patient with Hb H disease and intellectual disability

“…Regarding the duplication at 7p21, a 7p duplication syndrome has been described; its common phenotypic features include intellectual disability, hypotonia, large anterior fontanel, high/prominent forehead, microcephaly, hypertelorism, abnormally slanted palpebral fissures, flat nasal bridge, abnormal palate, low‐set ears, skeletal abnormalities and cardiovascular abnormalities [Chui et al, ], as well as autism [Goitia et al, ]. At least 20 cases of “pure” 7p duplications have been previously described [Papadopoulou et al, ], 4 of them microduplications [Chui et al, ; Preiksaitiene et al, ; Pebrel‐Richard et al, ; Goitia et al, ], which allowed to delimit and identify candidate genes, establishing a minimal critical region from 5,337,072 to 5,766,245 (NCBI Build 36) on chromosome 7p22.1, highlighting ACTB as the main candidate gene. Although this region is unaffected in our patient, many CNVs involving 7p22.3‐p22.1, some of them pathogenic, are listed in free databases.…”