Muscle cramps are a common problem characterized by a sudden, painful, and involuntary contraction of a muscle or muscle group. Most muscle cramps develop in the calf muscles, particularly in situations of prolonged exercise; however, some may be related to underlying systemic conditions such as the hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome. Muscle cramps appear to be the initial symptom of the HANAC syndrome; however, the clinical characteristics of these muscle cramps have rarely been described in detail.
We report a familial case of autosomal-dominant muscle cramps in four members of a Japanese family spanning across three generations. The muscle cramps were recognized as systemic symptoms of the HANAC syndrome associated with a novel COL4A1 pathogenic variant, NM_001845:c.1538G > A, p.(Gly513Asp). The four affected individuals indicated that the first episodes of the muscle cramps occurred in early childhood. In addition, they reported that the muscle cramps are characterized by an abrupt onset of severe pain without muscle contraction. The painful recurrent attacks occurred spontaneously in various muscles throughout the body, but rarely in the calf muscle. The muscle pain lasts for several minutes, cannot be ameliorated by stretching the affected muscle, and leaves a feeling of discomfort that lasts for 24–48 h. The serum creatine kinase levels of the patients were persistently elevated; however, their electromyography results did not reveal any specific abnormalities.
Recognition of the clinical characteristics of the muscle cramps in the HANAC syndrome may facilitate early diagnosis of the syndrome and enable proper treatment of the patients, improve their long-term outcomes, and facilitate the design and adaption of appropriate genetic counseling.
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- Nocturnal leg cramps in children: Incidence and clinical characteristics.J Natl Med Assoc. 1999; 91: 329-332
- Neurogenic muscle cramps.J Neurol. 2015; 262: 1814-1821
- HANAC Col4a1 mutation in mice leads to skeletal muscle alterations due to a primary vascular defect.Am J Pathol. 2017; 187: 505-516
- COL4A1 mutations and Hereditary Angiopathy, Nephropathy, Aneurysms, and Muscle Cramps.N Engl J Med. 2007; 357: 2687-2695
- Autosomal-dominant familial hematuria with retinal arteriolar tortuosity and contractures: A novel syndrome.Kidney Int. 2005; 67: 2354-2360
- Porencephaly in a fetus and HANAC in her father: Variable expression of COL4A1 mutation.Am J Med Genet A. 2015; 167: 156-158
- Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Genet Med. 2015; 17: 405-424
- Consideration of cosegregation in the pathogenicity classification of 164 genomic variants.Am J Hum Genet. 2016; 98: 1077-1081
- HELLP syndrome — Holistic insight into pathophysiology.Medicina (Kaunas). 2022; 58: 326
- Molecular advances in preeclampsia and HELLP syndrome.Int J Mol Sci. 2022; 23: 3851
Published online: March 14, 2023
Accepted: February 26, 2023
Received in revised form: February 13, 2023
Received: November 8, 2022
Publication stageIn Press Corrected Proof
© 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.