Introduction
KBG syndrome(OMIM 148050) is a rare genetic disease characterized by short stature, craniofacial dysmorphism, intellectual disability, macrodontia of the upper central incisors, and skeletal anomalies, and it was named after the initials of the last names of three original families.
Ankyrin repeat domain 11 gene(ANKRD11) has recently been identified as a causal factor of this syndrome, and intragenic variants including ANKRD11 have been reported to result in KBG syndrome.
In this article, we report six cases of KBG syndrome patients of our hospital.
Case
1. Case 1
A 4-year-old girl visited our department for developmental delay. Her height was 95cm(5th percentile(%ile)), and language developmental delay was apparent. Her parents were diagnosed with intellectual disability. On Bayley Scales of Infant and Toddler Development, she had low scores across all domains.
2. Case 2
A 5-year-old girl was Case 1’s sister. Her height was 108cm(25th %ile), and she could not get along well with her peers at the day care center. On Bayley scales, the general adaptive composite score was 82(12th %ile). The results of chromosomal microarray analysis(CMA) of Case 1 and 2 were normal, but the results of diagnostic exome sequencing test(DES) showed the same abnormalities as those of c.5711_5727dup variant in the ANKRD11 gene.
3. Case 3
A 17-month-old boy was referred for delayed development. His weight was 7.3kg(<3rd %ile). He showed brachycephaly, high arch palate, and macrodontia. The CMA results showed 16p11.2 microdeletion and the DES results showed c.5258C>A variant in the ANKRD11 gene.
4. Case 4
A 9-month-old boy was referred for delayed development. His height was 63cm(<3rd %ile), and his growth and development were severely delayed. He showed brachycephaly, triangular face, and tented upper lip.
5. Case 5
Case 4’s sister, a 21-month-old girl also had developmental delay. Her height was 74cm(<3rd percentile). She showed brachycephaly, triangular face, and macrodontia of deciduous teeth. Bone ages of both case 4 and 5 were lower than the actual age.
6. Case 6
A 37-year-old woman was the mother of Case 4 and 5. She showed developmental delay and intellectual disability. Her height was 140cm(50th %ile for 10-year-old). She showed brachycephaly, triangular face, macrodontia of upper central incisors, and scoliosis. In cases 4,5, and 6, the CMA showed normal results, and the Sanger sequencing confirmed the same c.2395-2398delAAAG variant in the ANKRD11 gene.
Conclusion
KBG syndrome was initially thought to be extremely rare. However, it seems to be underdiagnosed due to its mild features, especially in female patients.
So, we recommend that KBG syndrome be screened in patients with developmental delay, short stature and macrodontia.
Moreover, comprehensive rehabilitation will also be required for better consequences. |
