Discussion

In the present case, balloon angioplasty was effective for severe bilateral peripheral pulmonary artery stenosis associated with chondrodysplasia punctata. There are no detailed reports on balloon angioplasty for peripheral pulmonary artery stenosis in patients with chondrodysplasia punctata; the present case suggests that balloon angioplasty may be a suitable therapeutic option.

Severe isolated peripheral pulmonary artery stenosis is associated with several systemic diseases including Williams syndrome and Alagille syndrome. ^{Reference Allen, Driscall, Shaddy and Feltes4} Peripheral pulmonary artery stenosis also occurs in some patients with chondrodysplasia punctata, ^{Reference Fourie1} which is a rare group of diseases of skeletal dysplasia that include X-linked dominant chondrodysplasia Conradi-H FC;nermann type (CDPX2) and Keutel syndrome. Keutel syndrome is a rare autosomal recessive type of chondrodysplasia punctata with estimated prevalence of 1 in 1,000,000 births, almost all of which are associated with peripheral pulmonary artery stenosis. ^{Reference Cancela, Laizé, Conceição, Kempfe and Murshed2} There are two case reports of CDPX2 complicated by peripheral pulmonary artery stenosis, one of which describes severe peripheral pulmonary artery stenosis in a patient who died six months after birth. ^{Reference Trowitzsch, Richter, Eisenberg and Kallferz3} Although some adult cases of both syndromes have been reported, the natural history and optimal treatment of associated peripheral pulmonary artery stenosis remains unclear. ^{Reference Khosroshahi, Sahin, Akyuz and Ede5,Reference Posey, Burrage and Campeau6}

Peripheral pulmonary artery stenosis requires treatment in cases of severe bilateral or multiple stenoses leading to right ventricle pressure overload. The treatment options for peripheral pulmonary artery stenosis include both surgical repair and catheter intervention including balloon angioplasty and stent implantation. In our case, the initial balloon angioplasty was quite effective for peripheral pulmonary artery stenosis, and the restenosis has not occurred thereafter. Peripheral pulmonary artery stenosis is also associated with other systemic diseases such as Williams syndrome, it has been reported that the effectiveness of initial balloon angioplasty is approximately 50% and restenosis is frequently observed in Williams syndrome. ^{Reference Geggel, Gauvreau and Lock7} The arteries in Williams syndrome are histologically characterised by diffuse wall thickening consisting of intimal proliferation and medial dysplasia with hypertrophy, fibrosis, and nonparallel mosaic arrangement of smooth muscle cells. ^{Reference Zalzstein, Moes and Musewe8} These histological characteristics have been considered the basis for less successful pulmonary artery dilation in this syndrome. Although histological examination of the PAs was not performed in our patient, concentric arterial calcification in the area of the internal elastic plate of the PAs has been reported in patients with Keutel syndrome among chondrodysplasia punctata. ^{Reference Cranenburg, Van Spaendonck-Zwarts and Bonafe9} These differences in histological characteristics may contribute to the contrasting efficacy of balloon angioplasty and restenosis rates between chondrodysplasia punctata and Williams syndrome. For severe and stiff pulmonary artery stenosis, sufficient dilation cannot often be achieved unless a non-compliant balloon is used. In our case, effective dilation was achieved using a semi-compliant balloon. This phenomenon also suggests that pulmonary artery stenosis in chondrodysplasia punctata is easily dilated by balloon angioplasty histologically. In Williams syndrome, diffuse stenoses involving large segments of the pulmonary arterial tree are frequently encountered, ^{Reference Collins10} whereas in our case, the stenoses were short and limited to the bifurcations of the pulmonary arteries. The short extent of the stenosis may have contributed to the effectiveness of balloon angioplasty.

Because the general condition of the present patient was poor, we selected balloon angioplasty as a minimally invasive treatment. As the histological characteristics of the pulmonary artery in chondrodysplasia punctata and the risk of rupture and aneurysm formation were unknown. Therefore, we first performed dilation with a small-size balloon, followed by dilation with a balloon of approximately the same size as the reference pulmonary artery diameter. This allowed for effective dilation without vascular injury. Based on this case, a balloon with a size that is 3–3.5 times the diameter of the stenosis and is the same size as the reference artery can probably be used safely for dilation of peripheral pulmonary artery stenosis in chondrodysplasia punctata. Furthermore, we devised an intubation method for general anaesthesia that took into consideration the risk of injury to the spinal cord due to the instability of the cervical spine. Specifically, we avoided neck extension for intubation and performed the intubation under bronchial fibrescope guidance.

Based on the clinical course of our case, balloon angioplasty could be an effective treatment option for peripheral pulmonary artery stenosis associated with chondrodysplasia punctata. However, careful and long-term observation of restenosis is necessary, as long-term outcomes remain unknown and the specific histopathological findings of pulmonary artery stenosis in chondrodysplasia punctata are lacking. An accumulation of cases and pathological findings of peripheral pulmonary artery stenosis in chondrodysplasia punctata is necessary to clarify the long-term prognosis and optimal treatment for this condition.