The NALCN Beginners Guide

NALCN Health Condition FACT SHEET

Sospecha de un Diagnóstico

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Trastornos del neurodesarrollo y respiratorios en combinación con hipotonía, o en combinación con artrogriposis distal, son altamento sugestivos de una canalopatía asociada a NALCN. Una mutación del gen NALCN o en UNC80 (su subauxilar) podrá ser confirmada mediante técnicas genéticas de diagnóstico.
NALCN

The most common symptoms: 

Global developmental delay.  Intellectual disability that is caused by NALCN/UNC80 can rage from mild to severe. Children can have difficulty with language and motor development. Most children are not able to walk and they do not develop speech. Inherited and spontaneous mutations in the NALCN CONDITIONS cause devastating symptoms including hypotonia, developmental delay, inability to sit, stand or walk, severe intellectual disability, lack of speech developement, epilepsy and seizures and premature death in children

-Hypotonia. Weak muscle tone. s the medical term for decreased muscle tone. Newborn babies and young children with severe hypotonia are often described as being «floppy». 

-Breathing abnormalities. Episodes of disrupted respiratory rhythms, central and obstructive sleep apneas with recurrent hypoxia may be presented. Apneas and hypoapneas. Central apneas during sleep. Chronic respiratory dysfunctions should be anticipated and treated aggressively in infants with confirmed NALCN mutations, as they may adversely affect the neurodevelopmental outcome. It is recommended sleep studies (POLYSOMNOGRAPHY TEST) for all patients with NALCN/UNC80 gene mutations.

-Constipation

-Characteristic facies 

-In addition, CLIFAHDD Syndrome may exhibit distal arthogryposis. DA are a group of disorders that mainly involve the distal parts of the limbs. Arthrogryposis, describes congenital joint contracture in two or more areas of the body.Contractures in CLIFAHDD patients can be mild enough in some cases to have been overlooked, particularly in older children and young adults. 

 

Some patients also have: 

-Sleep disturbances

– Epileptic Seizures

-Movements disorders.

-Ataxia and episodic ataxia. Episodic ataxia consists of episodes of unsteadiness of movement and poor balance, vertigo (dizziness), nausea and headache. Children with episodic ataxia may typically walk without any problem but suddenly struggle to keep their balance. These attacks can by triggered by physical stress, fevers, exercise, warm wheather among others.

-Cerebellar dystrophy (MRI). This affects muscle coordination and balance. Symptoms include uncoordinated movement of the arms and legs, wide-based uncoordinated walk, back and forth tremor in the trunk of the body among others. 

-Eyes disorders IHPRF1. 

-Alteration in pain sensitivity

-Endocrine dysfunction. The sodium leak channel NALCN regulates cell excitability of pituitary endocrine cells. FASEB J. 2021, demonstrate that the sodium leak channel NALCN as well as its ancillary subunits are endogenously expressed in GH3 cells at least at the mRNA level. Results suggest that symptoms observed in patients with both the IHPRF1 and the CLIFAHDD syndromes that are complex may arise not only from an alteration of neuronal excitability, but also from endocrine defects 

-Early death in severe mutations..

WHAT DO CLIFAHDD AND IHPRF1&2 (NALCN/UNC80 genes)HAVE IN COMMUN?

The sodium leak channel NALCN is part of a large ion channel complex, consisting of multiple proteins including UNC80 and UNC79. (NALCN, UNC80 and UNC79 work together. If one of them does not work, the others will be affected as well.  NALCN forms a channel complex, interacting directly with UNC80, and indirectly with UNC79).