Introduction
Desbuquois dysplasia type 1 is a genetic skeletal disorder with autosomal recessive inheritance. The disorder can be identified by pronounced micromelic dwarfism, joint laxity, progressive scoliosis, and advanced carpotarsal ossification. Reference LeMerrer, Young, Stanescu and Maroteaux1 The disorder is very rare, with fewer than fifty cases documented to date. Desbuquois dysplasia type 1 (OMIM# 251450) is caused by homozygous or compound heterozygous pathogenic variants in the calcium-activated nucleotidase 1 gene on chromosome 17q25, while Desbuquois dysplasia Type 2 (OMIM# 615777) results from pathogenic variants in the Xylosyltransferase 1 (XYLT1) gene on chromosome 16p12. In addition to skeletal manifestations, there is multisystem involvement, including pulmonary, renal, and ocular findings. Reference Faivre2 Cardiac findings in the extremely rare Desbuquois dysplasia are seldom and superficially mentioned in studies. Pathogenic variants in the calcium-activated nucleotidase 1 gene encoding calcium-activated nucleotidase 1 are thought to cause changes in the structure of connective tissue by affecting glycosaminoglycan side chains, contribute to regulatory functions such as cell proliferation, differentiation and development, including the cardiovascular system. Defects in the proliferation and differentiation of cardiomyocytes with disruption of this structure are the cause of cardiovascular findings. Reference Paganini, Costantini, Superti-Furga and Rossi3 Aortopathy and atrioventricular valve prolapse, thought to result from defective proteoglycan production, have been described. Reference Baasanjav4 In addition, CHDs with left-to-right shunts, such as ventricular septal defect and atrial septal defect, which are common in the general population and not hemodynamically significant, have been reported. Reference Byrne5 The objective of this case report is to describe a 7-year-old patient diagnosed with both coronary-cameral fistula and Desbuquois dysplasia type 1, both of which are highly rare. To the best of our knowledge, this case is the first of its kind in the literature.
Case presentation
A 16-month-old male patient was referred to our centre due to dysmorphic facial features. He was the fourth live-born child of a healthy 34-year-old Gradiva 7 Parity 4 Abortion 3 (G7P4A3) mother and a healthy 33-year-old father. The parents were consanguineous (first cousins). The prenatal history was notable for short extremities. Physical examination revealed head circumference of 40 cm (standard deviation score (SDS): −6,09), body weight of 4000g (SDS: −10,8), and body length of 53.5 cm (SDS: −10,59). He had a round face with depressed nasal bridge, prominent eyes, and micrognathia. Short neck, pectus deformity, narrow thorax, and short extremities were noted as well. Radiographies displayed sagittal cleft in the spine, monkey wrench appearance of the femoral heads, Swedish key appearance of the proximal femur, wide metaphysis, phalangeal dislocations, radial deviation of the fingers, and osteopenic findings. A clinical diagnosis of Desbuquois dysplasia type 1 was established. Sanger sequencing was performed, which revealed a previously reported homozygous pathogenic variant in the calcium-activated nucleotidase 1 gene (ENST00000) c.898C>T; p.Arg300Cys, confirming the clinical diagnosis. Cranial ultrasonography displayed cerebellar vermis hypoplasia and enlarged lateral ventricles. In the follow-up, the patient had feeding difficulty and recurrent respiratory tract infections. He also had complaints of tachypnoea and shortness of breath. Anthropometric evaluation at the age of 7 years revealed a body weight of 6 kg (SDS: −23,98), body height of 61 cm (SDS: −12,27), and head circumference of 44.5 cm (SDS: −5,2). During the examination of the patient’s cardiovascular system, the heart was tachycardic, a 2/6 continuous murmur was noted at the left sternal border, and a loud S2 heart sound was present. An intermittent third heart sound was auscultated. The electrocardiogram demonstrated a peaked p wave indicative of right atrial dilation. The patient’s oxygen saturation was recorded at 96% at rest, declining to 92% with exertion. The telecardiography of the patient showed cardiomegaly and increased pulmonary blood flow.
The echocardiographic evaluation showed congestive enlargement of the heart chambers and dilatation of both atria. In M mode evaluation, left ventricular end-diastolic diameter was 32.5 mm (4.46 Z score). Left ventricular ejection fraction measured with M mode was 84%, and left ventricular fractional shortening was 52%. Both atrioventricular valves were observed to have prolapse and moderate regurgitation. A flow velocity of 4.5 m/s was obtained on the tricuspid regurgitation jet with continuous wave Doppler USG. The estimated right ventricular systolic pressure was calculated as 80 mmHg. No stenosis was observed on the pulmonary valve. A mean estimated pulmonary artery pressure of 45 mmHg was calculated on the mild pulmonary insufficiency flow with continuous wave Doppler USG. The main pulmonary artery width was measured as 22 mm (8.4 Z score).
The patient had a tricuspid aortic valve, dilated aortic root, and aneurysmatic ascending aorta. There was mild aortic insufficiency. The aortic annulus was measured as 19.3 mm (13.4 Z score), the sinus of Valsalva as 24 mm (11.8 Z score), the sino-tubular junction as 19.7 mm (10.9 Z score), and ascending aorta as 18 mm (7.5 Z score). Dilated left main coronary artery (3.2 mm- 4.1 Z score) and tortuous fistula line were seen. When the fistula line was scrutinised, it was observed that it was directed to the right atrium with both 2D image and colour Doppler USG. Colour Doppler echocardiography displayed a continuous flow pattern of left-to-right shunt over the fistula. Contrast-enhanced CT confirmed the coronary-cameral fistula extending from the left circumflex artery to the right atrium and severely dilated aortic root and ascending aorta (Fig. 1).
(a) Telecardiogram of patient: cardiomegaly and scoliosis, (b) 4-chamber echocardiography image: mitral and tricuspid valve insufficiency, dilatation of the right heart chambers, (c) 3D reconstructed CT: dilated sinus valgus (SVS), ascending aorta (AA), and left coronary artery, (d) 2D and colour doppler echocardiography images: coronary fistula tract extending from the left coronary artery to the right atrium and its opening.
The patient was observed to have a 5 mm secundum atrial septal defect, which was not thought to be haemodynamically significant. The patient’s family, who were offered catheter intervention to evaluate the existing pulmonary hypertension and fistula, did not accept the procedure due to risks and concerns. Therefore, the aetiology of pulmonary hypertension has not yet been clearly elucidated. The patient is being followed up in the clinic with beta-blockers, angiotensin receptor blockers, loop diuretics, and thiazide as palliatives.
Discussion
Desbuquois dysplasia type 1 is a rare genetic skeletal disorder with multisystem involvement. It is characterised by severe prenatal and postnatal growth retardation, joint laxity, short extremities, and progressive scoliosis. Pulmonary, renal, and ocular abnormalities have been reported. Although rare, cardiac complications, potentially due to defective proteoglycan production, have also been described. In this report, we describe a Desbuquois dysplasia patient with a coronary-cameral fistula. Coronary-cameral fistula is quite rare in the medical literature. In some studies, its frequency is reported as 0.1%. Reference Yamanaka and Hobbs6,Reference Vavuranakis, Bush and Boudoulas7 This prevalence tends to be significantly rarer in symptomatic patients, as it is predominantly identified incidentally in angiographic series. It is impossible to mention the frequency of Desbuquois dysplasia due to the low number of cases. This association is also worth noting.
The echocardiographic images suggest that the fistula-related shunt is haemodynamically significant. The fact that cardiac catheterisation could not be performed limits the cause-effect relationship. Because the patients have advanced skeletal and thoracic deformities, an increase in pulmonary artery pressure can be seen due to pulmonary causes. Mortality reported in the Desbuquois dysplasia patient group is mostly due to respiratory causes in early childhood. Reference Hall8
Another important situation in our patient is the presence of advanced aortopathy. The Z scores of the patient’s aortic measures are quite high due to the patient’s significantly low height and body weight. While the literature indicates that inaccurate Z scores can be deceptive in individuals with obesity, there is a lack of research concerning patients with exceptionally low body proportions. Reference Braley, Tang, Makil, Borroughs‐Ray and Collins9 Yet, there is aneurysmal dilatation at a level where the current literature suggests surgical intervention. However, due to the patient’s high surgical risk and the family’s reluctance to intervention, palliative treatments and recommendations are made. Due to the presence of very high-risk dilatation, dual therapy (beta-blockers + angiotensin receptor blockers) is applied. Reference Morris10
In conclusion, Desbuquois dysplasia type 1 is a rare genetic condition associated with possible morbidity and mortality due to multisystem involvement. Various cardiac findings, potentially caused by defective proteoglycan production, may be observed. Occasionally, associated congenital cardiac defects, such as coronary-cameral fistula, can contribute to a deterioration in the patient’s clinical status. A comprehensive cardiac assessment will significantly affect patient mortality and morbidity.
Learning Points
-
Desbuquois dysplasia type 1 is a rare genetic condition associated with possible morbidity and mortality due to multisystem involvement.
-
Various cardiac findings, potentially caused by defective proteoglycan production, may be observed. Occasionally, associated congenital cardiac defects, such as coronary-cameral fistula, can contribute to a deterioration in the patient’s clinical status.
-
A comprehensive cardiac assessment will significantly affect patient mortality and morbidity.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/S1047951125000551.
Acknowledgements
Acknowledgements should be extended to those individuals or institutions whose contributions to the study were limited or minimal.
Author contribution
Conception and design: Musa Öztürk, Hayrettin Hakan Aykan
Acquisition of data: Musa Öztürk, Merve Tanrısever Türk
Analysis and interpretation of data: Musa Öztürk, Hayrettin Hakan Aykan, Pelin Özlem Şimşek Kiper
All authors reviewed the results and approved the final version of this manuscript.
Financial support
The authors declare that the study received no funding.
Competing interests
The authors declare that there is no conflict of interest to disclose.
Ethical standard
Informed consent was obtained from patient and his family to share patient clinical information and imaging photographs anonymously for the scientific purposes.
Open access
