Ann Pediatr Endocrinol Metab.  2023 Mar;28(1):67-72. 10.6065/apem.2142134.067.

First female Korean child with Coffin-Lowry syndrome: a novel variant in RPS6KA3 diagnosed by exome sequencing and a literature review

• Song A
• Im M
• Kim MS
• Noh ES
• Kim C
• Jang J
• Lee SM
• Ki CS
• Cho SY
• Jin DK

• KMID: 2540790
• DOI: http://doi.org/10.6065/apem.2142134.067

Abstract

Coffin-Lowry syndrome (CLS, OMIM # 303600) is a rare X-linked disorder caused by mutations in RPS6KA3. CLS is characterized by facial dysmorphism, digit abnormalities, developmental delays, growth retardation, and progressive skeletal changes in male patients. Females with CLS are variably affected, complicating diagnosis. Here, we describe the clinical and molecular findings in a female Korean child with CLS and review the associated literature. A 5-year-old girl presented with short stature and developmental delays. She had a coarse facial appearance characterized by a prominent forehead, hypertelorism, thick lips, and hypodontia. She also had puffy tapering fingers and pectus excavatum. We performed exome sequencing and identified a novel, likely pathogenic, heterozygous variant, c.326_338delinsCTCGAGAC (p.Val109Alafs*10), in RPS6KA3 (NM_004586.2). This is the first Korean female genetically diagnosed with CLS. In contrast to the delayed bone age reported in previous studies, our patient showed advanced bone age and central precocious puberty. CLS should be considered as a differential diagnosis of short stature, tapering fingers, and developmental delay. We suggest that molecular techniques can be a useful tool for diagnosis of rare disorders such as CLS because such conditions are not simple, and the associated spectrum of phenotypes can vary.

Keyword

Coffin-Lowry syndrome; X-linked inheritance; Short stature; Developmental delay

Figure

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  Fig. 1. Puffy hands with typical tapering stubby fingers were seen in a girl with Coffin-Lowry syndrome at age 5 years 5 months.

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  Fig. 2. Sanger sequencing of the proband and her parents. A heterozygous, likely pathogenic variant, c.326_338delinsCTCGAGAC (p.Val109Alafs*10), in RPS6KA3 was found in the patient but was absent in her parents.

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  Fig. 3. Anterioposterior and lateral radiographs of the spine showing scoliosis with a 23° Cobb angle.

Reference

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