Pycnodysostosis with novel gene mutation and severe obstructive sleep apnoea: management of a complex case

Girbal, Inês; Nunes, Teresa; Medeira, Ana; Bandeira, Teresa

doi:10.1136/bcr-2013-200590

Cited by 13 publications

(23 citation statements)

References 13 publications

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“…Therefore, retrospective studies on pycnodysostosis seem to be inefficient to point out any strong correlation between phenotype and genotype. Girbal et al reported a novel mutation (c.953G>A, p.Cys318Tyr) in a non‐consanguineous family associated with rare and severe manifestations, including anemia, altered bone marrow, and life‐threatening obstructive apnea . Two siblings presented with that same mutation in our cohort.…”

Section: Discussionsupporting

confidence: 57%

“…More than 35 disease-causing mutations have already been identi- Cys318Tyr) in a non-consanguineous family associated with rare and severe manifestations, including anemia, altered bone marrow, and lifethreatening obstructive apnea. 17 Two siblings presented with that same mutation in our cohort. One of them had also a severe phenotype with 0.9 fractures per year in average, hearing impairment with delayed speech, sleep apnea, and hepatosplenomegaly.…”

Section: Phenotype-genotype Correlationmentioning

confidence: 99%

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Pycnodysostosis: Natural history and management guidelines from 27 French cases and a literature review

et al. 2019

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Pycnodysostosis is a lysosomal autosomal recessive skeletal dysplasia characterized by osteosclerosis, short stature, acro‐osteolysis, facial features and an increased risk of fractures. The clinical heterogeneity of the disease and its rarity make it difficult to provide patients an accurate prognosis, as well as appropriate care and follow‐up. French physicians from the OSCAR network have been asked to fill out questionnaires collecting molecular and clinical data for 27 patients issued from 17 unrelated families. All patients showed short stature (mean = −3.5 SD) which was more severe in females (P = .006). The mean fracture rate was moderate (0.21 per year), with four fractures in total average. About 75% underwent at least one surgery, with an average number of 2.1 interventions per patient. About 50% required non‐invasive assisted ventilation due to sleep apnea (67%). About 29% showed psychomotor difficulties and 33% needed a school assistant or adapted schooling. No patient had any psychological evaluation or follow‐up. Molecular data were available for 14 families. Growth hormone administration was efficient on linear growth in 40% of cases. We propose several axis of management, such as systematic cerebral MRI for Chiari malformation screening at diagnosis and regular psychological follow‐up.

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Section: Discussionsupporting

confidence: 57%

Section: Phenotype-genotype Correlationmentioning

confidence: 99%

Pycnodysostosis: Natural history and management guidelines from 27 French cases and a literature review

et al. 2019

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“…Although uncommon, sleep apnea, anesthetic complications, and deafness are other problems reported in patients with pycnodysostosis (Della Marca et al, 2012;Girbal et al, 2013;Testani et al, 2014;Valdes-Flores et al, 2014;Herd et al, 2015). One of five (20%) children in our series had snoring and sleep apnea.…”

Section: Discussionmentioning

confidence: 73%

Pycnodysostosis: mutation spectrum in five unrelated Indian children

Mandal

Ray

Saxena

et al. 2016

Clinical Dysmorphology

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“…Recently, it was detected in an African patient [36]. Another mutation, the c.580G>A (p.G194S), described once in a patient living in a region in the South of the Ceará State, was detected in an Italian patient so far [13].…”

Section: Discussionmentioning

confidence: 99%

Molecular analysis of the CTSK gene in a cohort of 33 Brazilian families with pycnodysostosis from a cluster in a Brazilian Northeast region

et al. 2016

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BackgroundPycnodysostosis is an autosomal recessive skeletal dysplasia, the prevalence of which is estimated to be low (1 per million). Nevertheless, in recent years we have found 27 affected individuals from 22 families in Ceará State, a region of the Brazilian Northeast, giving a local prevalence of 3 per million. This local prevalence associated with a high parental consanguinity, suggesting a possible founder effect, prompted us to perform a molecular investigation of these families to test this hypothesis.MethodsThe CTSK gene was sequenced by the Sanger method in the patients and their parents. In addition to 18 families from Ceará, this study also included 15 families from other Brazilian regions. We also investigated the origin of each family from the birthplace of the parents and/or grandparents.ResultsWe have studied 39 patients, including 33 probands and 6 sibs, from 33 families with pycnodysostosis and identified six mutations, five previously described (c.436G>C, c.580G>A, c.721C>T, c.830C>T and c.953G>A) and one novel frameshift (c.83dupT). This frameshift variant seems to have a single origin in Ceará State, since the haplotype study using the polymorphic markers D1S2344, D1S442, D1S498 and D1S2715 suggested a common origin. Most of the mutations were found in homozygosity in the patients from Ceará (83.3 %) while in other states the mutations were found in homozygosity in half of patients. We have also shown that most of the families currently living outside of Ceará have northeastern ancestors, suggesting a dispersion of these mutations from the Brazilian Northeast.ConclusionsThe high frequency of pycnodysostosis in Ceará State is the consequence of the high inbreeding in that region. Several mutations, probably introduced a long time ago in Ceará, must have spread due to consanguineous marriages and internal population migration. However, the novel mutation seems to have a single origin in Ceará, suggestive of a founder effect.Electronic supplementary materialThe online version of this article (doi:10.1186/s40001-016-0228-7) contains supplementary material, which is available to authorized users.

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Pycnodysostosis with novel gene mutation and severe obstructive sleep apnoea: management of a complex case

Cited by 13 publications

References 13 publications

Pycnodysostosis: Natural history and management guidelines from 27 French cases and a literature review

Pycnodysostosis: Natural history and management guidelines from 27 French cases and a literature review

Pycnodysostosis: mutation spectrum in five unrelated Indian children

Molecular analysis of the CTSK gene in a cohort of 33 Brazilian families with pycnodysostosis from a cluster in a Brazilian Northeast region

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