Varied imaging manifestations in EFEMP2 Related Cutis Laxa Associated Arterial Tortuosity
TJ03-TJ05
Correspondence
Jini Joseph,
“Menampadathil House” Maikkavu, P.O. Thamarassery, Calicut-673573, Kerala, India.
E-mail: jini.joseph@asterhospital.com
Case 1
An eight-month-old male baby was brought to the hospital by his parents due to poor weight gain, lower respiratory tract infection, and exertional dyspnoea (noticed by the parents) for one month. During the clinical examination, a grade-III ejection systolic murmur and end diastolic murmur were observed. A hyperdynamic apex and mild tachypnoea were also noted. Echocardiography (ECHO) was performed to investigate the suspicion of cardiac disease. The ECHO revealed aneurysmal aortic dilatation, moderate to severe aortic regurgitation, and was suggestive of Arterial Tortuosity Syndrome (ATS). Subsequently, a Computed Tomography (CT) pulmonary angiogram was conducted (Table/Fig 1),(Table/Fig 2),(Table/Fig 3),(Table/Fig 4),(Table/Fig 5),(Table/Fig 6),(Table/Fig 7),(Table/Fig 8).
At the time of discharge, the baby was stable and able to tolerate feeds. The caregivers were counselled regarding the progressive nature of the disease, its genetic aetiology and the prognosis.
Case 2
A 10-month-old female baby, who was developmentally normal, presented with complaints of breathing difficulty that worsened in the lying down position and improved in the sitting position, as well as decreased urine output for the past two weeks. There was no significant antenatal, natal or postnatal history. The baby had a history of head sweating and a suck-rest-suck cycle. There was no history of cough.
Upon clinical examination, cutis laxa was observed along with a hyperdynamic apex, cardiomegaly, an ejection systolic murmur, an end diastolic murmur, tachypnoea and subcostal retractions. ECHO showed dilated aorta from the sinuses to the proximal arch, aneurysmal dilation of the ascending aorta, tortuous descending aorta, severe mitral regurgitation, aortic regurgitation and pulmonary artery hypertension. Multidetector Computed Tomography (MDCT) pulmonary angiogram was advised to further assess the anatomy of the vessels (Table/Fig 9),(Table/Fig 10),(Table/Fig 11),(Table/Fig 12).
Initially, the baby was stable and able to tolerate feeds. However, four months after the diagnosis, the patient developed severe respiratory distress. Venous blood gas analysis showed severe respiratory acidosis. The baby was intubated and started on inotropes and diuretics. While being extubated, the patient was unable to tolerate Bilevel Positive Airway Pressure (BiPAP) and experienced bradycardia, desaturation, and ultimately succumbed to death despite resuscitative measures.
Case 3
A male baby, born at term and appropriate for gestational age, was referred from an outside hospital at 78 hours of life (HOL) due to respiratory distress. Clinical examination at 48 HOL revealed a systolic murmur. Chest X-ray showed well-expanded lung fields and normal cardiac shadows. Sepsis screen and blood culture were negative. ECHO was performed, which revealed a dilated main pulmonary artery and ascending aorta, myxomatous Arteriovenous (AV) valve leaflets, severe bilateral peripheral Pulmonary Stenosis (PS), turbulent flows across the arch vessels and descending aorta, Right Pulmonary Artery (RPA) stenosis, and moderate Pulmonary Arterial Hypertension (PAH). Due to suspicion of ATS, a CT pulmonary angiogram was conducted. The CT pulmonary angiogram showed levocardia, mild tortuosity and elongation of the aortic arch, tortuosity of the origin and course of bilateral common carotid and left subclavian arteries, tortuous aberrant right subclavian artery, dilated main pulmonary artery (12.8 mm) with narrowing of the origin of the left pulmonary artery (3.4 mm), and mild tortuosity of the descending thoracic aorta and inferior mesenteric artery was (Table/Fig 13),(Table/Fig 14),(Table/Fig 15). The baby remained haemodynamically stable and had good oral feeding tolerance, leading to his discharge.
Genetic testing revealed that all of these babies had a similar genetic result, with a mutation in the Epidermal Growth Factor-containing Fibulin-like Extracellular Matrix Protein 2 (EFEMP2) gene causing Autosomal Recessive Cutis Laxa type 1B (ARCL1B) associated with arterial tortuosity. Specifically, a homozygous missense variation in exon 7 of the EFEMP2 gene (chr11:65637447T>G; c.608A>C) resulting in the substitution of alanine for aspartic acid at codon 203 (p.Asp203Ala) was identified, confirming the diagnosis of ARCL1B (Table/Fig 16).