兰尼碱受体 1 (RYR1) 基因的致病性变异可导致多种肌肉表型，从恶性高热到轻度非进行性肌病，再到严重的先天性肌病。常染色体显性遗传和隐性遗传均可发生，更严重的形式通常表现为隐性遗传。然而，由于基因较大和表型异质，基因型-表型相关性很复杂。我们介绍了一名患有严重先天性肌病的 6 岁患者，携带从健康母亲遗传的杂合致病性 RYR1 变异。通过全基因组测序，我们发现了第二种深内含子 RYR1 变异，该变异最近在另一名患有严重先天性肌病的患者中得到描述，并被证明会影响剪接。分离分析证实这些变体是复合杂合的。我们将患者的表型与文献中的患者以及我们中心的另外五名具有复合杂合 RYR1 变异体的患者进行了比较。主要重叠特征包括先天性发病、主要肌张力减退和肌酸激酶（CK）水平正常，而总体临床表现差异很大。有趣的是，两名携带新内含子剪接变体的患者都表现出非常严重的病程。基因组测序的更广泛使用将为更好的基因型-表型相关性开辟道路。

Pathogenic variants in the ryanodine receptor 1 (RYR1) gene are causative for a wide spectrum of muscular phenotypes, ranging from malignant hyperthermia over mild, non-progressive to severe congenital myopathy. Both autosomal dominant and recessive inheritance can occur, with the more severe forms usually showing recessive inheritance. However, genotype-phenotype correlations are complicated due to the large size of the gene and heterogeneous phenotypes. We present a 6-year-old patient with severe congenital myopathy, carrying a heterozygous pathogenic RYR1 variant inherited from the healthy mother. Through whole genome sequencing we identified a second, deep intronic RYR1 variant that has recently been described in another patient with severe congenital myopathy and shown to affect splicing. Segregation analyses confirmed the variants to be compound heterozygous. We compared our patient's phenotype to that of the patient from the literature as well as five additional patients with compound heterozygous RYR1 variants from our center. The main overlapping features comprised congenital onset, predominant muscular hypotonia, and normal creatine kinase (CK) levels, while overall clinical expression varied substantially. Interestingly, both patients carrying the new intronic splice variant showed a very severe disease course. More widespread use of genome sequencing will open the way for better genotype-phenotype correlations.