Pycnodysostosis (PYCD, OMIM: 265800) is an uncommon, autosomal recessive condition, first described by Maroteaux and Lamy in 1962 (Maroteaux and Lamy 1962). PYCD is also known as Toulouse-Lautrec disease, after the French artist Henri de Toulouse-Lautrec who may have had the disease (Hodder et al. 2015). Responsible gene for this phenotype (CTSK) codes the enzyme cathepsin K that is important for normal osteoclasts' function. The characteristic features of pycnodysostosis are short stature, bone fragility with osteosclerosis, acro-osteolysis of the distal phalanges, delayed suture closure, obtuse mandibular angle, prominent eyes and brachydactyly. Craniofacial abnormalities such as maxillofacial malformations, narrow palate and dental anomalies frequently accompany pycnodysostosis. Airway problems have also been described in pycnodysostosis patients (Testani et al. 2014). Congenital choanal atresia was first described by Roederer in 1755 (Hengerer and Strome 1982). Choanal atresia can occur alone or it can be a component of other syndromes such as CHARGE syndrome, and other craniosynostosis syndromes (Crouzon syndrome, Pfeiffer syndrome etc.). Here, we describe a pycnodysostosis case with bilateral choanal atresia in addition to other findings. A 23-year-old woman from a consanguineous Turkish family was referred to us because of her craniofacial dysmorphism, short stature, unilateral hearing loss and bilateral choanal atresia. Clinical examination showed frontal bossing, bilateral frontotemporal grooving, proptosis, prominent nose, retro-micrognathia, narrow palate, wrinkled skin, brachydactyly, broad thumbs, bilateral sandal gap deformity (Fig. 1a). Her height was 133 cm, (below 3rd percentile) and her mental status seemed normal. Pedigree analysis showed autosomal recessive pattern with two more similar patients in the family. Radiographic examinations showed metopic craniosynostosis, open wide cranial sutures, hypoplasia of terminal phalanges and acro-osteolysis, sclerosis of vertebral bodies and anterior scalloping (spool-shaped vertebrae), Madelung deformity of forearm, and Erlenmayer flaks deformity of long bones (Fig. 1b–e). Genomic DNA was isolated from peripheral blood samples of the patient using MagnaPure LC DNA Isolation Kit-Large Volume and MagnaPure LC instrument (Roche Applied Science, Mannheim, Germany). CTSK gene mutation analysis was performed by sequencing of the coding exons and the exon-intron boundaries of the genes. Sequencing was carried out with Miseq V2 chemistry on MiSeq instrument (Illumina California, USA). Analysis was performed with IGV software. c.934C > T (p.R312X) homozygote mutation was found in the 8th exon of the CTSK gene. She had complained of nasal congestion and was refered to the otorhinolaryngology department. During endoscopic examination, bilateral choanal atresia with unilateral pin point perforation were found (Fig. 1f). On computed tomography, soft tissue was detected in the posterior portion of the nasal cavity, which was obliterated to choana and also open cranial sutures were seen (Fig. 1b,d). Endoscopic transnasal repair of choanal atresia was performed. Cathepsin K is a cysteine protease that plays an important role in degradation of collagen type I and other bone proteins (Motyckova and Fisher 2002). Cathepsin K is a major lysosomal protease in bone resorption that is highly expressed in osteoclasts. Pycnodysostosis is caused by homozygous or compound heterozygous mutations in the CTSK gene. In pycnodysostosis osteoclast numbers and demineralizing function are normal; however, degradation of the organic matrix is insufficient (Gelb et al. 1996). Various mutations in the CTSK gene were identified in patients. In our case, nonsense c.934C > T (p.R312X) homozygote mutation was observed and this mutation was reported previously in Turkish patients (Arman et al. 2014). This mutation occurs by changing of the C residue of CGA encoding arginine to T resulted in TGA, stop codon on CTSK gene. Choanal atresia is a congenital abnormality and it can be unilateral or bilateral. The bilateral defect is more rare and generally present in a newborn as a medical emergency. Hence, bilateral choanal atresia is uncommon in adults and there are only a few cases reported in the literature. Respiratory involvement, such as obstructive sleep apnea syndrome, upper airway narrowing and respiratory distress, is frequent in patients with pycnodysostosis (Testani et al. 2014). However, pycnodysostosis with bilateral choanal atresia have not been reported earlier in the literature. Choanal atresia can be a component of a genetic syndrome. Medical genetics consultation should be requested when choanal atresia is not isolated. None.
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Mar 1, 2022
Lauren S Starnes + 3
Open Access
