Seckel syndrome presenting with complete heart block

Abstract

Seckel syndrome is a rare autosomal recessive disorder characterized by facial dysmorphic features known as bird-headed dwarfism. Only about 100 cases have been reported. Cardiac anomalies have been described as a potential association with Seckel syndrome. We report a 21-year-old woman with Seckel syndrome and epilepsy who presented with status epilepticus. She was hypotensive and bradycardic. Her electrocardiogram showed complete heart block. She was placed on transcutaneous pacer with no response. A transvenous pacemaker was placed before inserting a suitable permanent pacemaker for her size. This is the third case of complete heart block associated with Seckel syndrome and raises concern about the potential association.

Seckel syndrome is a rare (<1:10,000 live births) autosomal recessive disorder known as bird-headed dwarfism.¹ It is characterized by intrauterine growth retardation, dwarfism, bird-headed facial appearance, microcephaly, and mental retardation.² The syndrome was described by Seckel in 1960, and only about 170 cases have been reported in the literature.^3,4 Seckel syndrome has been associated with different congenital abnormalities like congenital hearing loss as well as cardiac abnormalities. The association of Seckel syndrome with complete heart block (CHB) has been reported twice, by Çelenk et al and Unal et al.^5,6 Here, we report the third case of Seckel syndrome associated with CHB.

CASE PRESENTATION

A 21-year-old woman, known to have Seckel syndrome with neurodevelopmental delay and seizure disorder, presented to the emergency department with recurrent generalized tonic-clonic seizures and intractable vomiting of 1-day duration. Upon arrival, she had an altered level of consciousness, and her heart rate was in the 20s. Her electrocardiogram showed CHB (Figure 1). Laboratory workup showed acute kidney injury (creatinine of 0.8 mg/dL vs baseline of 0.5 mg/dL), with a potassium of 6.4 mmol/L. She was started on intravenous fluids due to the obvious volume depletion on physical exam as well as dopamine and isoproterenol drips with no improvement of her heart rate. Her potassium level was corrected as well, with no reversing of the CHB. She was also placed on a transcutaneous pacer with no adequate capturing. A transvenous pacemaker was placed in the emergency room, and the patient was admitted to the pediatric intensive care unit given her small size for her age (she weighed 26 kg). The patient’s clinical course significantly improved with steady capture and good cardiac output, stable systemic blood pressures, and perfusion. Transthoracic echocardiography showed normal systolic and diastolic functions. No cardiac anomaly was found. Neurologically, her mental status also improved with no further seizure activity. A suitable permanent pacemaker for her size was unavailable at our facility, and she was transferred to the University of Texas Southwestern Medical Center in Dallas, where she got a permanent pacemaker and was discharged home in stable condition.

Figure 1.

(a) Complete heart block on presentation. (b) Ventricularly paced rhythm.

DISCUSSION

Systemic abnormalities associated with Seckel syndrome include central nervous system, hematopoietic, endocrine, cochlear, and cardiovascular anomalies.^1,2 Cardiovascular manifestations are rare in this disease, with around 12 reported cases. Most are congenital cardiac anomalies; however, arrhythmias like severe sinus bradycardia and CHB have been reported as well.^4–6 Reported anomalies include tetralogy of Fallot,⁷ tricuspid atresia,⁸ atrioventricular canal defect,⁹ Moyamoya-like vasculopathy,¹⁰ patent ductus arteriosus,¹¹ complex heart lesion,¹¹ and atrial septal defect.¹² Howanietz et al reported a case of congenital heart failure with atrial septal defect, ventricular septal defect, and patent ductus arteriosus.¹³

Among the arrhythmias reported, Ramasamy et al reported a case of severe sinus bradycardia that required a pacemaker.⁴ There was no clear mechanism for this severe sinus bradycardia.⁴ Two cases of CHB were reported in the literature.^5,6 Unal et al reported the first patient with Seckel syndrome who underwent a pacemaker insertion while under anesthesia for CHB at 6 months of age.⁵ Çelenk et al reported the second case in a patient who was undergoing a cochlear implant. This patient had a permanent pacemaker as well.⁶ To our knowledge, ours is the third case of CHB reported in association with Seckel syndrome.

Seckel syndrome is usually due to recessive mutations in the gene encoding ataxia telangiectasia and Rad3-related protein, a protein kinase responsible for the deoxyribonucleic acid damage response pathway; however, other gene mutations have also been identified.² The ataxia telangiectasia and Rad3-related protein gene is involved in sensing DNA damage and activating the DNA damage checkpoint, leading to cell cycle arrest.¹⁴ This gene is related to a second checkpoint-activating kinase, serine/threonine kinase, an ataxia telangiectasia mutated gene that leads to cell cycle arrest, DNA repair, or apoptosis when activated. It has been described to have a role in cardiac remodeling with different effects early and late post-myocardial infarction.¹⁵ Yet, no studies have been done to describe the relationship with specialized cardiac muscle cells and CHB. Could it be apoptosis for specialized cardiac muscle cells?

Theoretically, a large cohort study should be done to establish the association of different cardiac problems with Seckel syndrome. However, since the disease is rare and only three cases of CHB have been reported, including our case, we cannot establish a clear association. More cases are needed to study the possible mechanism and to further understand the potential association. Genomic studies for these different cases might be helpful in this rare disease entity and might help establish such an association. We recommend a cardiac evaluation for every case of Seckel syndrome.