Case Reports

. 2022 Feb 17;48(1):29.

doi: 10.1186/s13052-021-01194-2.

Alternating Hemiplegia of Childhood: neurological comorbidities and intrafamilial variability

Piero Pavone¹, Xena Giada Pappalardo^{2

3}, Naira Mustafa^{4

5}, Sung Yoon Cho⁶, Dong Kyu Jin⁶, Gemma Incorpora⁷, Raffaele Falsaperla⁸, Simona Domenica Marino⁹, Giovanni Corsello¹⁰, Enrico Parano², Martino Ruggieri¹¹

Affiliations

¹ Pediatric Clinic, Department of Clinical and Experimental Medicine, University Hospital A.U.O. "Policlinico-Vittorio Emanuele" of Catania, Catania, Italy. ppavone@unict.it.
² National Council of Research, Institute for Research and Biomedical Innovation (IRIB), Unit of Catania, Catania, Italy.
³ Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Catania, Italy.
⁴ Department of Paediatrics, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
⁵ Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
⁶ Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁷ Pediatric Clinic, Department of Clinical and Experimental Medicine, University Hospital A.U.O. "Policlinico-Vittorio Emanuele" of Catania, Catania, Italy.
⁸ Unit of Pediatrics and Neonatal Intensive Therapy, Department of Promotion of Maternal and Infantile and Internal Medicine Health, and Specialist Excellence "G. D'Alessandro", University of Palermo, Palermo, Italy.
⁹ Unit of Pediatrics, Neonatology and Neonatal Intensive Care, and Pediatric Emergency, AOU "Policlinico", PO "San Marco", University of Catania, Catania, Italy.
¹⁰ Mother and Child Department, Operative Unit of Pediatrics and Neonatal Intensive Therapy, University of Palermo, Palermo, Italy.
¹¹ Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, AOU "Policlinico", PO "G. Rodolico", Catania, Italy.

PMID: 35177115
PMCID: PMC8851838
DOI: 10.1186/s13052-021-01194-2

Case Reports

Alternating Hemiplegia of Childhood: neurological comorbidities and intrafamilial variability

Piero Pavone et al. Ital J Pediatr. 2022.

. 2022 Feb 17;48(1):29.

doi: 10.1186/s13052-021-01194-2.

Authors

Affiliations

¹ Pediatric Clinic, Department of Clinical and Experimental Medicine, University Hospital A.U.O. "Policlinico-Vittorio Emanuele" of Catania, Catania, Italy. ppavone@unict.it.
² National Council of Research, Institute for Research and Biomedical Innovation (IRIB), Unit of Catania, Catania, Italy.
³ Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Catania, Italy.
⁴ Department of Paediatrics, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
⁵ Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
⁶ Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁷ Pediatric Clinic, Department of Clinical and Experimental Medicine, University Hospital A.U.O. "Policlinico-Vittorio Emanuele" of Catania, Catania, Italy.
⁸ Unit of Pediatrics and Neonatal Intensive Therapy, Department of Promotion of Maternal and Infantile and Internal Medicine Health, and Specialist Excellence "G. D'Alessandro", University of Palermo, Palermo, Italy.
⁹ Unit of Pediatrics, Neonatology and Neonatal Intensive Care, and Pediatric Emergency, AOU "Policlinico", PO "San Marco", University of Catania, Catania, Italy.
¹⁰ Mother and Child Department, Operative Unit of Pediatrics and Neonatal Intensive Therapy, University of Palermo, Palermo, Italy.
¹¹ Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, AOU "Policlinico", PO "G. Rodolico", Catania, Italy.

PMID: 35177115
PMCID: PMC8851838
DOI: 10.1186/s13052-021-01194-2

Abstract

Background: Alternating of Childhood (AHC) is an uncommon and complex disorder characterized by age of onset before 18 months with recurrent hemiplegia of one or either sides of the body or quadriplegia. The disorder is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene. In AHC neurological co-morbidities are various and frequently reported including developmental delay, epilepsy, tonic or dystonic spells, nystagmus,autonomic manifestations with intrafamilial variability.

Case presentation: Clinical and genetic findings of a couple of twins (Family 1: Case 1 and Case 2) and a couple of siblings (Family 2: Case 3 and Case 4) coming from two different Italian families affected by AHC were deeply examined. In twins of Family 1, a pathogenic variant in ATP1A3 gene (c.2318A>G) was detected. In siblings of Family 2, the younger brother showed a novel GRIN2A variant (c.3175 T > A), while the older carried the same GRIN2A variant, and two missense mutations in SCNIB (c.632 > A) and KCNQ2 (1870 G > A) genes. Clinical manifestations of the four affected children were reported along with cases of AHC drawn from the literature.

Conclusions: Hemiplegic episode is only a sign even if the most remarkable of several and various neurological comorbidities in AHC affected individuals. Molecular analysis of the families here reported showed that clinical features of AHC may be also the result of an unexpected genetic heterogeneity.

Keywords: Alternating hemiplegia of childhood (AHC); Case report; Comorbidities; Epilepsy; GRIN2A.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

**Fig. 1**
a Case 3. EEG at 4 years old showing multifocal spike/waves prevalently in fronto-centro-parietal regions. b Case 3. EEG at 4 years old showing multifocal spike/waves with generalization

**Fig. 2**
a Case 4. EEG at 8 years old showing multifocal spike/waves prevalently in the frontal regions. b Case 4. Ictal EEG showing multifocal spikes and waves

See this image and copyright information in PMC

References

1. Verret S, Steele JC. Alternating hemiplegia in childhood: a report of eight patients with complicated migraine beginning in infancy. Pediatrics. 1971;47(4):675–680. doi: 10.1542/peds.47.4.675. - DOI - PubMed
1. Krageloh I, Aicardi J. Alternating hemiplegia in infants: report of five cases. Dev Med Child Neurol. 1980;22(6):784–791. doi: 10.1111/j.1469-8749.1980.tb03746.x. - DOI - PubMed
1. Bourgeois M, Aicardi J, Goutieres F. Alternating hemiplegia of childhood. J Pediatr. 1993;122(5 Pt 1):673–679. doi: 10.1016/S0022-3476(06)80003-X. - DOI - PubMed
1. Mikati MA, Kramer U, Zupanc ML, Shanahan RJ. Alternating hemiplegia of childhood: clinical manifestations and long-term outcome. Pediatr Neurol. 2000;23(2):134–141. doi: 10.1016/S0887-8994(00)00157-0. - DOI - PubMed
1. Aicardi J, Bourgeois M, Goutieres F. Alternating hemiplegia of childhood: clinical findings and diagnostic criteria. In: Andermann F, Aicardi J, Vigevano F, editors. Alternating Hemiplegia of Childhood. New York: Raven Press; 1995. pp. 3–18.

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Alternating Hemiplegia of Childhood: neurological comorbidities and intrafamilial variability

Affiliations

Alternating Hemiplegia of Childhood: neurological comorbidities and intrafamilial variability

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Supplementary concepts

LinkOut - more resources

Full Text Sources

Miscellaneous