Neuropediatrics 2018; 49(S 02): S1-S69
DOI: 10.1055/s-0038-1675994
Posters
Neurogenetics
Georg Thieme Verlag KG Stuttgart · New York

P 308. Autosomal Recessive Mutations in the NALCN Gene: A Rare Cause of a Severe Developmental Disorder with Facial Dysmorphia, Epilepsy and Cheyne–Stokes/Biot’s Respiration with Central Apneas

Iciar Sánchez-Albisua
1   Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University’s Children Hospital, University of Duisburg-Essen, Essen, Germany
,
Nuria Brämswig
2   Institute of Human Genetics, University’s Hospital, University of Duisburg-Essen, Essen, Germany
,
Adela Della Marina
1   Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University’s Children Hospital, University of Duisburg-Essen, Essen, Germany
,
Heike Kölbel
1   Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University’s Children Hospital, University of Duisburg-Essen, Essen, Germany
,
Katrin Rupprich
1   Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University’s Children Hospital, University of Duisburg-Essen, Essen, Germany
,
Alma Küchler
2   Institute of Human Genetics, University’s Hospital, University of Duisburg-Essen, Essen, Germany
,
Tim M. Strom
3   Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany
,
Hermann Josef Luedecke
2   Institute of Human Genetics, University’s Hospital, University of Duisburg-Essen, Essen, Germany
3   Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany
4   Institut of Human Genetics, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
,
Dagmar Wieczorek
2   Institute of Human Genetics, University’s Hospital, University of Duisburg-Essen, Essen, Germany
4   Institut of Human Genetics, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
,
Ulrike Schara
1   Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University’s Children Hospital, University of Duisburg-Essen, Essen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
30 October 2018 (online)

 

Background: Biallelic loss of function mutations in the NALCN gene have been described in the literature. It causes a disorder leading to hypotonia, mental retardation, facial dysmorphia, cachexia, and other variable clinical abnormalities. However, only very few affected cases have been published so far and the described phenotype is miscellaneous in some aspects.

Aim: Phenotyping of a patient with a biallelic loss of function mutation in the NALCN gene.

Patients and Methods: A 6-year-old girl presented with facial dysmorphias, convergent strabismus, severe mental retardation, unachieved ambulation, and lacking language development along with autistic traits. She showed muscular hypotonia with dystrophy (BMI: −2.29Z, < P1) and normocephaly. From the age of 6 years, epileptic attacks occurred (myoclonias, drop seizures). The mother reported irregular breathing and breathing pauses with subsequent arousals in the form of chest retractions/noisy breathing.

Results: Trio exome sequencing showed a nonsense and a frameshift mutation [c.2629delC; p.(Gln877Asnfs*16); c.3022C>T; p.(Arg1008Ter)] in the NALCN gene. Under valproate, lamotrigine, and especially ketogenic diet, the patient has been seizure free for 5 years. Valproat could be discontinued successfully. The ketogenic diet also led to an improvement of dystrophy (BMI: P6). Despite slow progress in development, she had not yet achieved any ability to walk or speak. The polygraph showed a continuous image of Cheyne–Stokes/Biot’s breathing with central apnea for 10 seconds during sleep and wakefulness without significant desaturation.

Conclusion: The NALCN gene encodes a nonselective sodium leak channel and is mainly expressed in the central nervous system. Facial dysmorphia, epilepsy, dystrophy, and irregular breathing may be indicative of mutations in the NALCN gene. The ketogenic diet can have a positive effect on both epilepsy and dystrophy. We believe that the NALCN gene should be included in the panel for epilepsies with developmental disorder.