Chromosome 17q23.1-Q23.2 Deletion Syndrome

A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome.

Clinical Features

Ballif et al. (2010) reported 7 unrelated patients with chromosome 17q23.1-q23.2 deletion syndrome ranging in age from 8 months to 16.5 years. All individuals had mild to moderate developmental delay. Other common features included low birth weight (5 of 7), microcephaly or relative microcephaly (5 of 7), and postnatal growth retardation (5 of 7). Heart defects, either patent ductus arteriosus or atrial septal defect, were present in 6. All had hand and foot anomalies, including long, thin fingers and toes, and 4 had variable musculoskeletal anomalies, such as ossification defects, hypoplasia of the patellas, and deep or shallow acetabula. Two had aggressive behavior, and 2 had hearing loss. Five had eye anomalies, such as chalazion, stellate pattern of the irides, retinopathy of prematurity, and esotropia, but the authors concluded that the anomalies were incidental, since they affected different components of the eye. Although all individuals had at least mild dysmorphic facial features, there was no characteristic constellation of features that were specific to the disorder. Some of the musculoskeletal abnormalities were reminiscent of the small patella syndrome (147891).

In 2 sibs with congenital clubfoot, both of whom were less than 3 years of age, Alvarado et al. (2010) identified a 2.2-Mb chromosome 17q23.1-q23.2 deletion. Neither sib had the heart defects, facial dysmorphism, or cognitive and behavioral abnormalities previously reported in patients with the same deletion. Alvarado et al. (2010) identified patients in 3 other families segregating clubfoot who had duplication of the same chromosome 17q region (613618).

Ballif et al. (2010) identified 7 unrelated patients with a heterozygous deletion of chromosome 17q23.1-q23.2 using microarray-based comparative genomic hybridization. All deletions were confirmed by FISH and BAC analysis and were apparently de novo. One individual had a 2.8-Mb deletion, whereas the remaining 6 had 2.2-Mb deletions. The 2.2-Mb deletions were flanked by homologous segmental duplications in the same orientation, consistent with nonallelic homologous recombination. The proximal breakpoint of the 2.8-Mb deletion fell between 2 segmental duplications. The phenotype of the patient with the larger deletion did not appear to differ from that of those with the 2.2-Mb deletion. Ballif et al. (2010) postulated that the conserved transcription factors TBX2 (600747) and TBX4 (601719) located within this chromosome region may be involved, since they are known to play numerous roles in development.

Nimmakayalu et al. (2011) reported a girl with a 17q22-q23 deletion who had congenital microcephaly, thyroglossal duct cyst, sensorineural hearing loss, dysmorphic features, developmental delay, and pulmonary hypertension.

Kerstjens-Frederikse et al. (2013) studied 20 consecutive patients with idiopathic or heritable pulmonary arterial hypertension (PAH), 6 of whom had accompanying mental retardation and dysmorphic features. By array CGH, 3 of the 6 were found to have 17q23 deletions.

German et al. (2019) reported a neonate with severe respiratory failure, bilateral clenched fists, posteriorly rotated and low-set ears, widely spaced and underdeveloped nipples, broad halluces, hypoplastic toenails, and bilateral clinodactyly of the second toes. By rapid exome sequencing, he was found to have a 2-Mb deletion (chr17:59,290,909-61,353,248, GRCh37) involving 14 genes, including TBX4. A lung biopsy on day 8 of life showed marked arrest of lung maturation consistent with acinar dysplasia.

Suhrie et al. (2019) reported 2 neonates with pulmonary hypoplasia, one of whom (infant B) had the 2.2-Mb deletion on 17q with a missense variant (R288K; rs11760393) in the ABCA3 gene (601615) on the other allele.

Of 26 patients with lethal lung disorders, Karolak et al. (2019) found that 8 had deletions on 17q that involved the TBX4 gene. Inheritance was de novo in 2 cases, inherited in 1 case, and unknown in the remaining 5 cases. Karolak et al. (2019) also reported 7 controls with the same deletion and identified an additional 6 patients who did not have pulmonary hypoplasia but had other issues, including developmental delay, hearing impairment, and variable dysmorphic features. One of the latter patients had a pneumothorax at birth and another developed severe childhood-onset pulmonary arterial hypertension and interstitial lung disease, in the setting of autism spectrum disorder and microcephaly. Karolak et al. (2019) argued that those affected with lung hypoplasia harbored at least one noncoding single nucleotide variant in the predicted lung-specific enhancer region, which was absent in 13 control individuals with overlapping deletions but without any structural lung disease.