Lethal metatropic dysplasia: a case report

Kumar, Beena; Kannu, Peter; Savarirayan, Ravi; Chan, Yuen

doi:10.1080/00313020601123854

Cited by 3 publications

(4 citation statements)

References 11 publications

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“…Since the first description of a patient presenting with radiological manifestation of MD in 1893 [Kaufmann, 1893], 81 other MD patients have been reported in the literature thus far [Beck et al, 1983;Belik et al, 1985;Boden et al, 1987;Kozlowski et al, 1988;Shohat et al, 1989;Manouvrier-Hanu et al, 1995;O'Sullivan et al, 1998;Mukherjee and Ghosh, 2002;Leet et al, 2006;Kumar et al, 2007;Wada et al, 2007] (the patients reported by Ech-Cherif El Kettani et al [2003] do not fit with the diagnosis of MD).…”

Section: Introductionmentioning

confidence: 85%

Revisiting metatropic dysplasia: Presentation of a series of 19 novel patients and review of the literature

Geneviève

Merrer

Feingold

et al. 2008

American J of Med Genetics Pt A

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Metatropic dysplasia (MD-OMIM: 156530 and 250600) is a rare chondrodysplasia characterized by short limbs with limitation and enlargement of joints and usually severe kyphoscoliosis, first described in 1893. Up until now, 81 other patients have been reported. The phenotypic variability of MD has led to a classification based on radiological anomalies dividing into three different types: a lethal autosomal recessive form, an autosomal recessive non-lethal form and a non-lethal autosomal dominant form with less severe radiographs manifestations and a better clinical outcome. Here, we report on clinical and radiological features of 19 novel MD patients. We describe new radiological features, including precocious calcification of hyoid and cricoid cartilage, irregular and squared-off calcaneal bones and severe hypoplasia of the anterior portion of first cervical vertebrae. In addition, the observation of an overlap between the autosomal recessive non-lethal form and the non-lethal autosomal dominant form, the rarity of sibship recurrences and the observation of vertical transmissions of MD in the literature argue in favor of an autosomal dominant mode of inheritance for all MD types. This hypothesis is reinforced by the use of the statistical single ascertainment method that rejects the hypothesis of an autosomal recessive mode of inheritance responsible for MD. Therefore, we propose that recurrence in sibs is due to gonadal mosaicism.

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Section: Introductionmentioning

confidence: 85%

Revisiting metatropic dysplasia: Presentation of a series of 19 novel patients and review of the literature

Geneviève

Merrer

Feingold

et al. 2008

American J of Med Genetics Pt A

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“…In patient 14, already described in the literature, a diagnosis of probable lethal bone dysplasia was made in utero , and the pregnancy was interrupted at 23 weeks of gestation: the post mortem examination led to the diagnosis of MD [1,15]. The TRPV4 mutation (Q239H) this patient had is novel and neither of the parents showed the same change.…”

Section: Resultsmentioning

confidence: 99%

TRPV4 related skeletal dysplasias: a phenotypic spectrum highlighted byclinical, radiographic, and molecular studies in 21 new families

Andreucci

Aftimos

Alcausin

et al. 2011

Orphanet J Rare Dis

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BackgroundThe TRPV4 gene encodes a calcium-permeable ion-channel that is widely expressed, responds to many different stimuli and participates in an extraordinarily wide range of physiologic processes. Autosomal dominant brachyolmia, spondylometaphyseal dysplasia Kozlowski type (SMDK) and metatropic dysplasia (MD) are currently considered three distinct skeletal dysplasias with some shared clinical features, including short stature, platyspondyly, and progressive scoliosis. Recently, TRPV4 mutations have been found in patients diagnosed with these skeletal phenotypes.Methods and ResultsWe critically analysed the clinical and radiographic data on 26 subjects from 21 families, all of whom had a clinical diagnosis of one of the conditions described above: 15 with MD; 9 with SMDK; and 2 with brachyolmia. We sequenced TRPV4 and identified 9 different mutations in 22 patients, 4 previously described, and 5 novel. There were 4 mutation-negative cases: one with MD and one with SMDK, both displaying atypical clinical and radiographic features for these diagnoses; and two with brachyolmia, who had isolated spine changes and no metaphyseal involvement.ConclusionsOur data suggest the TRPV4 skeletal dysplasias represent a continuum of severity with areas of phenotypic overlap, even within the same family. We propose that AD brachyolmia lies at the mildest end of this spectrum and, since all cases described with this diagnosis and TRPV4 mutations display metaphyseal changes, we suggest that it is not a distinct entity but represents the mildest phenotypic expression of SMDK.

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“…Various bone abnormalities have been histologically demonstrated including chondrocyte and matrix defects [Boden et al, 1987; Kumar et al, 2007], an uncoupling of endo and perichondrial ossification and growth plate abnormalities [Kozlowski et al, 1976; Spranger and Maroteaux, 1990]. These are all generalized bone architectural abnormalities which in some way must contribute to the progressive scoliosis.…”

Section: Discussionmentioning

confidence: 99%

“…5). A postmortem diagnosis of metatropic dysplasia was made following a detailed clinical examination and skeletal survey [Kumar et al, 2007].…”

Section: Methodsmentioning

confidence: 99%

Metatropic dysplasia: Clinical and radiographic findings in 11 patients demonstrating long‐term natural history

Kannu

Aftimos²,

Mayne

et al. 2007

American J of Med Genetics Pt A

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We report on the largest long-term follow-up study in metatropic dysplasia incorporating data collected over a 37-year period. Case summaries from 11 patients are presented, ranging from 20 weeks of gestation to age 70 years, characterizing the natural history. All patients were seen through the Victorian Clinical Genetics Service and the Southern Cross Bone Dysplasia Centre. Our data lend little support for the current clinical classification of metatropic dysplasia and highlight a spectrum of severity in this rare condition, which we propose has an autosomal dominant inheritance pattern. Complications such as upper respiratory obstruction secondary to laryngo-tracheal dysfunction need to be carefully monitored for in infancy because this is a preventable cause of mortality. The progression of a thoracic kyphoscoliosis in this condition is often relentless and resistant to surgical treatment. Other causes of morbidity include cervical instability, hearing loss, and functional impairments resulting from degenerative joint deformity. Intellectual outcome in all surviving cases has been normal. Final adult heights ranged from 107 to 135 cm.

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Lethal metatropic dysplasia: a case report

Cited by 3 publications

References 11 publications

Revisiting metatropic dysplasia: Presentation of a series of 19 novel patients and review of the literature

Revisiting metatropic dysplasia: Presentation of a series of 19 novel patients and review of the literature

TRPV4 related skeletal dysplasias: a phenotypic spectrum highlighted byclinical, radiographic, and molecular studies in 21 new families

Metatropic dysplasia: Clinical and radiographic findings in 11 patients demonstrating long‐term natural history

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