With the advent of comparative genomic hybridization (CGH) technology, more patients with microduplications or micro deletions are being reported. Herein, we report an 11-year-old girl with 7p22.1 microdeletion who presented with short stature and intellectual disability. She was the second born child to non-consanguineous parents, born at full term with a birthweight of 2 kg. Ventricular septal defect and patent foramen ovale were detected after birth and cardiac surgery was undertaken at one year of age (weight 7 kg). At four years of age, she was detected with intellectual disability and short stature (height of 87 cm) with a normal karyotype (46,XX).

At 11 years, her weight was 31.3 kg (about -1 SD) height 134.5 cm (<2 SD), with distinctive facial features including long face, high forehead, arched eyebrows, long eyelashes, flat nose bridge, broad nose, upturned lip, downturned corners of the mouth and pointed chin. Small brown pigmentation, snaggle teeth, sagging shoulders and shoulder girdle muscle bulk, scar on the chest wall, flexion of the left thumb (contracture), clinodactyly and abnormal dermatogly-phics were also noted with Tanner stage 4 breast development. Wechsler intelligence scale showed intellectual disability with a score of 56.

Laboratory data showed hypertriglyceridemia (3.64 mmol/L). The levels of follicle stimulating hormone, luteinizing hormone, prolactin, progesterone and estradiol were consistent with sexual development. The level of insulin-like growth factor 1, insulin like growth factor binding protein 3, corticotrophin, cortisol, liver function, renal function and thyroid function were in normal range. An abdominal ultrasound was normal. Copy number variation (CNV) analysis (MyGenostics Gene Technology Co., Ltd. China) was performed and a 1.673 Mb microdeletion (chr7: 5 147 686-6 820 998) at chromosome 7p22.1 was found. No similar deletion was noted from her parents by CNV analysis and her parents refused for FISH analysis.

About 30 cases with 7p22.1 microdeletion have been earlier reported [1,2]. The common clinical features in these patients included intellectual disability (58.3%), distinctive facial features (44%), short stature (33.3%), microcephaly (22.2%), hernia (14.8%), hypotonia (14.8%), VSD (13%) and abnormal extremities (7.4%). Joint laxity, bilateral radial abnormalities, PFO, pulmonary artery dilatation and high palate were also reported in one case.

The specific relationship between genotype and phenotype in 7p22.1 deletion is still unknown. The deleted region in index case contained 36 genes, including RNF216, AIMP2, RAC1, PMS2 and ACTB, which are known pathogenic genes. Mutations in RNF216, AIMP2, RAC1 and ACTB are associated with intellectual disability [1-5]. The expression levels of ACTB are linearly correlated with the ACTB gene copy number and influence the amount of b-actin, which is involved in cell motility and expressed in all eukaryotic cells [1,2]. Thus, the haploinsufficiency of ACTB may be accountable for intellectual disability and other clinical features in 7q22.1 microdeletion [2]. Postnatal growth retardation, high forehead, hypertelorism, arched eyebrows, broad nose with large tip, hypoplastic scapulas, and congenital heart defects in index case were consistent with the features of ACTB gene deficiency. However, ACTB gene was not deleted in few cases who showed intellectual disability, implying that other genes (e.g., RAC1 gene) or even non-coding RNA coded in this region may contribute to the clinical features of this rare condition.

In summary, 7p22.1 microdeletion syndrome should be considered in patients with intellectual disability, distinctive facial features, microcephaly, short stature, inguinal hernia, hypotonia, and congenital heart disease and confirmed with genetic testing.

Contributors: CCZ: conceived the study; HYL and JXF: manuscript writing and literatures review.  All authors approved the final manuscript.

Funding: National Natural Science Foundation (81170787 & 81371215) and Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents (2014);
Competing interest: None stated.

REFERENCES

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2. Shimojima K, Narai S, Togawa M, Doumoto T, Sangu N, Vanakker OM, et al. 7p22.1 microdeletions involving ACTB associated with developmental delay, short stature, and microcephaly. Eur J Med Genet. 2016;59:502-6.

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