Abstract:

Objective: To analyze a case of Lamb-Shaffer syndrome(LAMSHF) with short stature and delayed language and motor development as the main manifestation,and summerize data of the disease in data bank for improving the understanding of this disease. Methods: A male child aged 9 year and 3 months with severe short stature and delayed language and motor development admitted to our hospital was analyzed. Their clinical data were collected, and the genomic DNA was extracted from whole blood of the children and their parents for whole exome sequencing and DNA Sanger sequencing verification. Meanwhile, relevant literature was reviewed to analyze the pathogenesis, clinical characteri-stics, diagnosis and therapy and prognosis of LAMSHF. Results: The height of the boy was 108.7 cm [-4.82 standard deviation (SD)], weight was 17.1 kg (<-2.1 SD), body mass index was 14.5 kg/m² (-1.1 SD), and gross motor and language development 1-year delay. Laboratory test showed the insulin-like growth factor was 74 ng/mL (-2.14 SD), growth hormone challenge test suggested growth hormone and the remaining tests were all normal. Whole exome sequencing revealed that Seq[GRCh37]del(12)(p12.1s; p11.1) involved multiple known pathogenic genes including SOX5, with a copy number deletion of at least 10.4 Mb, and which were not detected before, so the copy number variant was a novel mutation. The mutation was assessed by ACMG guidelines as probable pathogenic (PS2+PM1). Therefore Lamb-Shaffer syndrome was diagnosed. Literature reviewing indicated that 11 LAMSHF-related studies included 1 domestic study and 10 foreign studies, with a total of 75 patients. The diagnosis of LAMSHF depended on genetic testing, and there is no clear genotype-phenotype correlation. The improvement of the patient's intellectual disability depended on rehabilitation treatment. Due to the high risk of epilepsy, ocular signs, and hypotonia in this disease, and the tendency to have tumors, growth hormone should be avoided for treatment of short stature. Patients with this disease currently had a poor prognosis. Conclusions: The boy with LAMSHF carried 12p12.1 deletion, which is the largest deletion and is never reported, presenting severe short stature. Short stature children with abnormal intelligence need to be screened for gene mutation and copy number variation of SOX5, and growth hormone therapy should be avoided due to potential risk of tumorigenesis.

Key words: Short stature, Language retardation, Motor retardation, Lamb-Shaffer syndrome