Abstract

Weiss–Kruszka syndrome (WSKA; OMIM#618619) is a rare condition with multiple congenital anomalies. This study describes a patient with WSKA from Northern China. The patient wasa 9-year-9-month-old boy presenting with growth retardation (growth velocity: 3–4 cm/year at school age), delayed motor and speech development, and eating difficulty. The patient’s weight was 22 kg (<3rd centile), and his height was 125.6 cm (<3rd centile) at the first visit. He had craniofacial anomalies characterized by heavily arched eyebrows, mild bilateral ptosis, inner epicanthal folds, uneven teeth, macrodontia of the upper central incisors, and low-set ears. A transverse palmar crease was observed on the right palm. The serum insulin-like growth factor-1 level was 73.1 ng/mL (normal range: 74–388 ng/mL). His bone age was 9–10 years. Cranial magnetic resonance imaging results revealed a small pituitary gland. Trio whole-exome sequencing was performed because of the patient’s nonspecific dysmorphic features and a phenotype indistinguishable from many other inherited disorders with growth retardation. A de novo splicing variant, c.6833-2A > T, was identified in the ZNF462 gene (NM_021224). Recombinant human growth hormone therapy was started (dose, 0.15 IU/kg/day) and administered as daily subcutaneous injections. His growth velocity increased (5 cm/6 months). This case has been added to the limited number of publications reporting WSKA. This study also examined the genotypic and phenotypic landscape of WKSA, providing clinical and genetic data to support the haploinsufficiency of the ZNF462 gene, as postulated by previous studies.