Case Report
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Mar 16, 2021; 9(8): 1853-1862
Published online Mar 16, 2021. doi: 10.12998/wjcc.v9.i8.1853
A three-year clinical investigation of a Chinese child with craniometaphyseal dysplasia caused by a mutated ANKH gene
Jia-Li Wu, Xiao-Li Li, Shu-Mei Chen, Xiao-Ping Lan, Jin-Jin Chen, Xiao-Yan Li, Wei Wang
Jia-Li Wu, Shu-Mei Chen, Xiao-Yan Li, Department of Otolaryngology and Head and Neck Surgery, Shanghai Children’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200062, China
Xiao-Li Li, Department of Radiation Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Xiao-Ping Lan, Molecular Diagnostic Laboratory, Shanghai Children’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200062, China
Jin-Jin Chen, Department of Child Healthcare, Shanghai Children’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200062, China
Wei Wang, Shanghai AhCare Consulting, Shanghai 20120, China
Author contributions: Wu JL and Li XY were the patient’s otolaryngologists, reviewed the literature and contributed to manuscript drafting; Li XL was the patient’s radiologist, performed the patient’s radiography and interpreted the image findings at the Shanghai Children’s Hospital; Chen SM reviewed the literature and contributed to the follow-up of the patient; Lan XP performed the genetic analysis and database search; Chen JJ was the pediatrician, reviewed the case and followed up the patient; Wang W was the clinical geneticist, responsible for the analysis and interpretation of the gene testing results; Li XY and Wang W were responsible for the revision of the manuscript for important intellectual content and approval of the manuscript; Li XY and Wang W are co-corresponding authors; all authors issued final approval for the submission of this article.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: All authors declare no conflict of interests.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Wei Wang, MD, MPH, PhD, Shanghai AhCare Consulting, No. 500 Furonghua Road, Pudong New District, Shanghai 20120, China. angei200598@126.com
Received: August 12, 2020
Peer-review started: August 12, 2020
First decision: December 8, 2020
Revised: December 31, 2020
Accepted: January 23, 2021
Article in press: January 23, 2021
Published online: March 16, 2021
Abstract
BACKGROUND

Craniometaphyseal dysplasia (CMD) is a rare genetic disorder. Autosomal dominant CMD (AD-CMD) is caused by mutations in the ANKH gene. Affected individuals typically have distinctive facial features including progressive thickening of the craniofacial bones. Treatment for AD-CMD primarily consists of surgical intervention to release compression of the cranial nerves and the brain stem/spinal cord. To alleviate progression of the clinical course and improve the quality of life in children waiting to undergo the necessary surgery, we investigated clinical changes in a diagnosed patient with AD-CMD over three years.

CASE SUMMARY

A 17-mo-old boy presented with progressive nasal obstruction, snoring and hearing loss symptoms. Physical examination showed enlargement of the head circumference and clinical features such as wide nasal bridge, paranasal bossing, widely spaced eyes with an increased bizygomatic width, and a prominent mandible. The patient underwent otolaryngological examination, endoscopy, hearing test, laboratory examination of phosphorus and bone metabolism, cranial and femoral computed tomography, X-ray and next-generation sequencing. The patient was diagnosed with AD-CMD due to p.Phe377 deletion (c.1129_1131del) on exon 9 of the ANKH gene. After adherence to a prescribed low-calcium diet, the boy’s alkaline phosphatase (ALP) levels continuously decreased to within the normal range. However, after 14 mo of dietary intervention, his parents altered his diet to an intermittent low-calcium diet to include milk and eggs. The patient’s ALP was slightly higher than normal after the dietary change but remained close to the normal range. His serum osteocalcin changed to within normal levels after dietary regulation for 33 mo. His serum combined beta C-terminal telopeptide of type I collagen also continuously decreased after the nutritional intervention, although still slightly higher than normal levels. Despite fluctuating blood test results, the boy’s nasal symptoms were markedly relieved and steadily improved after dietary intervention. No significant changes were found in the craniofacial bones by cranial radiography. Close monitoring of clinical features is still ongoing. Calcitriol treatment is currently under consideration and a surgical procedure is planned as necessary in the future.

CONCLUSION

We herein report the first Chinese case of AD-CMD with heterozygous mutation of p.Phe377 deletion (c.1129_1131del) on the ANKH gene. Biochemical alterations were significantly improved after dietary intervention indicating that a low-calcium diet may be applied in pediatric AD-CMD patients with ANKH mutations to help alleviate phenotypic manifestations and improve the quality of life before surgical intervention. Further large scale studies are needed to replicate these findings and to establish the appropriate timing for nutritional and surgical interventions

Keywords: ANKH gene mutation, Clinical investigation, Craniometaphyseal dysplasia, Case report, Child

Core Tip: Craniometaphyseal dysplasia is a rare genetic disorder. It has been found to be caused by mutations in the ANKH gene with an autosomal dominant inheritance pattern. If untreated, hyperostosis and sclerosis of the skull may lead to cranial nerve compressions resulting in deafness, blindness and facial palsy. Surgical interventions would usually be needed in severe cases such as these. We herein report the first Chinese case with heterozygous mutation of p.Phe377 deletion (c.1129_1131del) on the ANKH gene. We investigated the clinical changes in this patient who underwent nutritional intervention between 3 and 33 mo. Biochemical alterations were significantly changed after dietary intervention. Phenotypic manifestations were markedly alleviated. A low-calcium diet may help slow the clinical course in children and improve the quality of life before the necessary surgery. Further large scale studies are needed to establish the appropriate timing of nutritional and surgical interventions.