The NAXCARE (NAXos disease and Cardiocutaneous Assessment and Registry for Evaluation) is a global initiative designed to collect, store, and analyze clinical outcomes data on patients with Naxos disease and related cardiocutaneous syndromes (CCS). This registry aims to fill the gaps in clinical knowledge, enhance treatment approaches, and improve patient outcomes by systematically documenting disease progression, genetic profiles, and patient care pathways. The following methodology outlines the registry's design, data collection protocols, management, security measures, and anticipated contributions to research and clinical practice.

Naxos disease variant (Carvajal syndrome) is a cardiocutaneous genetic disease caused by Plakoglobin and Desmoplakin gene mutation, and usually manifests with woolly hair, palmoplantar keratoderma, and cardiomyopathy, and are found to have a high risk for uncontrolled arrhythmia. An observational retrospective cohort study was conducted at King Faisal Specialist Hospital & Research Center in Riyadh, Saudi Arabia, a tertiary care hospital, which included 10 Saudi pediatric patients with clinical manifestations that indicate Naxos disease variant. The medical records of the patients were analyzed such as Echocardiography parameters (for ventricular function assessment), electrocardiography (ECG), 24-h Holter (for arrhythmias), and genetic analysis results were collected to confirm the medical diagnosis. We report 10 Saudi pediatric patients with Naxos disease variant who presented with severe dilated cardiomyopathy manifestation. All the patients had woolly hair, and half had palmoplantar keratoderma. They all had severely dilated and depressed left ventricular systolic function, and nine of them also had depressed right ventricular systolic function. Frequent premature ventricular tachycardias (PVCs) were reported in nine cases, and an implantable cardioverter defibrillator (ICD) was implanted in 3 patients for uncontrolled ventricular tachycardias. Moreover, four patients underwent heart transplantation, and three died suddenly while waiting for a heart donation. Finally, in 8 patients, genetic studies were homozygous for Desmoplakin gene (DSP), confirming the diagnosis. Naxos disease variant is accompanied by high risk of arrhythmia and sudden cardiac deaths, so family members of proband need an extensive genetic workup for identification of gene carriers for counseling, especially in our Arab countries where consanguineous marriage is common. Moreover, hair and skin phenotypes in a child should alert for signs of cardiomyopathy manifestation.

A 10-year-old Indian female presented with persistently short, sparse scalp hair since birth, with no subsequent growth. Clinical examination revealed tightly coiled, light-colored, and diffusely thinned scalp hair, along with partial loss of the lateral third of the eyebrows. The disease is a rare genetic disorder characterized by structural abnormalities of the hair shaft, presenting as tightly curled hair, and exists in two primary forms: autosomal dominant hereditary woolly hair and the rarer autosomal recessive familial woolly hair. It has also been associated with keratosis pilaris, canaliform nail dystrophy, interdental spacing, recurrent bullous impetigo, and a few diseases like Naxos disease and Carvajal syndrome. This rare case, involving multiple siblings in an Indian setting, highlights the clinical spectrum of congenital woolly hair and underscores the need for further genetic investigations to elucidate its molecular basis. RésuméUne fillette indienne de 10 ans présentait des cheveux courts et clairsemés depuis sa naissance, sans repousse ultérieure. L’examen clinique a révélé des cheveux clairs, frisés et clairsemés, ainsi qu’une perte partielle du tiers latéral des sourcils. Cette maladie est une maladie génétique rare caractérisée par des anomalies structurelles de la tige pilaire, se manifestant par des cheveux bouclés serrés. Elle existe sous deux formes principales : la forme laineuse héréditaire autosomique dominante et la forme laineuse familiale autosomique récessive, plus rare. Elle a également été associée à la kératose pilaire, à la dystrophie unguéale canaliforme, à l’espacement interdentaire, à l’impétigo bulleux récurrent et à quelques maladies comme la maladie de Naxos et le syndrome de Carvajal. Ce cas rare, impliquant plusieurs frères et sœurs en Inde, met en évidence le spectre clinique de la forme laineuse congénitale et souligne la nécessité de recherches génétiques complémentaires pour élucider ses bases moléculaires.

The electrocardiogram (ECG) remains a cornerstone of modern cardiology, providing rapid, non-invasive, and widely accessible diagnostic insights. While ECG interpretation is an essential skill for clinicians, certain patterns can be subtle or atypical, posing diagnostic challenges. In our previous review (doi.org/10.3390/jpm12111754), we explored several uncommon ECG syndromes with significant clinical implications. However, the spectrum of electrocardiographic abnormalities extends far beyond those initially discussed. In this second installment, we expand our discussion of rare and underrecognized ECG syndromes, including Long QT, Jervell and Lange-Nielsen, Romano-Ward, Andersen-Tawil, Timothy, Short QT, and Twiddler's syndromes, as well as Noonan, Barlow's, Bundgaard, BRASH, Carvajal, Naxos, and Danon disease. We highlight their clinical context, characteristic findings, and implications for diagnosis and management. These conditions range from acute, life-threatening emergencies requiring immediate intervention to chronic electrical disorders necessitating long-term monitoring and risk stratification. By broadening our focus, we aim to enhance awareness and recognition of these entities, ultimately improving patient outcomes through timely and accurate diagnosis.

Carvajal syndrome, a rare autosomal recessive disorder caused by mutations in the DSP gene, is characterised by woolly hair, palmoplantar keratoderma, and left ventricular dilated cardiomyopathy. Although less frequently reported, noncompaction cardiomyopathy can co-occur, further complicating the clinical picture. Early diagnosis and management are crucial due to the high risk of progressive heart failure and sudden cardiac death in affected individuals. A 13-year-old male with autism presented with a 1.5-month history of persistent cough and worsening clinical symptoms, including hepatomegaly and signs of heart failure. Physical examination revealed woolly hair, patchy alopecia, nail anomalies, and ectodermal dysplasia. Echocardiography demonstrated left ventricular dilated cardiomyopathy, noncompaction, and a severely reduced ejection fraction of 23%. Initial management in the paediatric intensive care unit included inotropic support, diuretics, and beta-blockers. Genetic analysis confirmed a homozygous c.7912G > T nonsense variant in the DSP gene, establishing the diagnosis of Carvajal syndrome. The patient was referred to an advanced cardiac centre. Carvajal syndrome involves multisystem manifestations, with prominent dermatologic and cardiovascular features. Unlike Naxos disease, which primarily affects the right ventricle, Carvajal syndrome predominantly involves the left ventricle, as observed in this case. Notably, left ventricular noncompaction was a striking feature in our patient, further exacerbating cardiac dysfunction and complicating the clinical course. Although noncompaction cardiomyopathy is less frequently reported in Carvajal syndrome, its pronounced presence in this case underscores the phenotypic variability and severity of myocardial involvement. Intensive care management with a multidisciplinary approach was essential in stabilising this patient. Genetic testing confirmed the diagnosis and highlighted the importance of molecular diagnostics in differentiating cardiocutaneous syndromes.