Serpentine fibula syndrome: expansion of the phenotype with three affected siblings

Rosser, Elisabeth; Mann, Nick; Hall, Christine; Winter, R M

doi:10.1097/00019605-199604000-00002

Cited by 23 publications

(29 citation statements)

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“…5 She had persistent ductus arteriosus and intestinal malrotation (which were repaired), an atrial septal defect, splenomegaly, bilateral sensorineural hearing loss, recurrent respiratory infections and corneal diameters of 11-12 mm without glaucoma. Facial dysmorphism was evident with high-arched eyebrows, hypertelorism, full checks, left ptosis and micrognathia.…”

Section: Clinical Reportsmentioning

confidence: 99%

“…Only the female proband had serpentine fibulae. 5 The pronounced bowing of the long bones in SFPKS evoked comparisons with Melnick Needles syndrome in one report 5 and forms the basis of the current classification of the condition alongside the filaminopathy disorders in the 2010 Nosology and Classification of Genetic Skeletal Disorders. 6 Mutations in FLNA, the locus mutated in Melnick Needles syndrome, have been excluded in one individual with SFPCKS.…”

Section: Introductionmentioning

confidence: 99%

“…7 In the report of the familial instance of SFPKS, it was noted that the three siblings had significant phenotypic overlap with the autosomal dominant condition known as Hajdu-Cheney syndrome (HCS). 5 The presentation of HCS is variable but typically includes acro-osteolysis of the distal phalanges, generalised osteoporosis, craniofacial anomalies, short stature, premature tooth loss and cystic kidneys. 8 Simpson et al 9 and Isidor et al 10 have recently identified truncating mutations in exon 34 of NOTCH2 in several families and sporadic individuals with HCS.…”

Section: Introductionmentioning

confidence: 99%

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Serpentine fibula polycystic kidney syndrome is part of the phenotypic spectrum of Hajdu–Cheney syndrome

et al. 2011

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Serpentine fibula polycystic kidney syndrome (SFPKS; MIM600330) is a rare skeletal dysplasia that has polycystic kidneys and dysmorphic facies as additional defining phenotypic components. The nosological classification of this disease has been debated as the condition shares features common to other skeletal dysplasias such as Melnick Needles syndrome (MNS; MIM309350) and Hajdu-Cheney Syndrome (HCS; MIM102500). Here, two previously reported cases of SFPKS are presented with emphasis on their phenotypic evolution. With the recent discovery that HCS is caused by mutations in NOTCH2, DNA from the both cases was examined and both were found to have truncating mutations in exon 34 of NOTCH2. The phenotypic evolution of SFPKS and this molecular analysis strongly suggest that SFPKS is part of the phenotypic spectrum of HCS and should no longer be classified as a distinct disease entity.

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Section: Clinical Reportsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serpentine fibula polycystic kidney syndrome is part of the phenotypic spectrum of Hajdu–Cheney syndrome

et al. 2011

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“…The facial dysmorphisms include hypertelorism, micrognathia and microstomia, low-set ears and a short neck and there may also be generalised hirsutism. Cardiovascular anomalies include aortic valve disease (stenosis and incompetence), ASD, VSD and premature arterial calcification (Rosser et al, 1996).…”

Section: Hjcys-notch2mentioning

confidence: 99%

Syndromes and Diseases Associated with the Notch Signalling Pathway

Turnpenny

2014

Encyclopedia of Life Sciences

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The Notch signalling pathway refers to a highly conserved complex cell interaction mechanism, playing a crucial role in metazoan development, which eventually dictates cell fates through the implementation of differentiation, proliferation and apoptosis, ultimately influencing organ formation and morphogenesis by unlocking specific developmental programmes. In mammals, the regulation of neurogenesis, myogenesis, angiogenesis, haematopoiesis and epithelial–mesenchymal transition are all crucially influenced by Notch signalling and to date 10 genes, either core components of the pathway or signalling targets, are implicated in a diverse group of human Mendelian diseases/syndromes when mutated in the germline. These can be broadly grouped into those conditions dominated by axial skeletal defects – the spondylocostal dysostoses; those with predominantly vascular or cardiovascular abnormalities – Alagille syndrome, NOTCH1 ‐related congenital cardiac anomalies and CADASIL; Hajdu–Cheney syndrome, a multisystem disorder dominated by skeletal anomalies, and neurological degeneration – Alzheimer disease type 3. Notch signalling is also widely implicated in somatic genomic mutational events leading to cancer and malignancy, the best known example of which is T‐cell acute lymphoblastic leukaemia. Key Concepts: Notch signalling is a highly conserved pathway in metazoan development. The Notch gene family encodes cell surface transmembrane receptors which mediate cellular functions through direct cell–cell contact. The activation of membrane‐bound Notch results in proteolytic cleavage Notch intracellular domain (NICD), which translocates to the nucleus. The Notch intracellular domain (NICD) converts downstream targets from transcriptional repressors to transcriptional activators. Notch signalling determines cell fates in neurogenesis, myogenesis, angiogenesis, haematopoiesis and epithelial–mesenchymal transition. A key role of the Notch signalling pathway is in the developmental integrity of somitogenesis. Syndromes caused by germline mutations in Notch pathway genes include spondylocostal dysostosis, Alagille and Hajdu–Cheney. Syndromes with predominantly (cardio)vascular effects due to mutations in Notch pathway genes include congenital heart disease and CADASIL. A form of familial presenile dementia (Alzheimer disease type 3) is due to mutated PSEN1 , a Notch pathway gene. Somatic mutations in certain Notch pathway genes are increasingly being shown to contribute to various cancerous conditions.

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“…The phenotype of MNS overlaps with that of serpentine fibula-polycystic kidney syndrome (SFPKS: MIM 600330) a rare condition characterized by growth retardation, dysmorphism, hirsutism, short neck, elongated bowed fibulae, metatarsus adductus, polycystic kidneys, deafness and normal intelligence. To date, only three sporadic cases (two females, one male) have been reported as having SFPKS (Dereymaeker et al, 1986;Exner, 1988) The sibs reported by Rosser et al (1996) with this diagnosis are considered by some to be examples of Frank-ter Haar syndrome despite the dysmorphism being atypical for this condition (Maas et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Phenotypic overlap in Melnick–Needles, serpentine fibula–polycystic kidney and Hajdu–Cheney syndromes: a clinical and molecular study in three patients

Albano

Bertola

Barba³

et al. 2007

Clinical Dysmorphology

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Several disorders characterized primarily by anomalies of the skeleton have recently been shown to be caused by mutations in the X-linked gene, FLNA. One of these conditions, the Melnick-Needles syndrome exhibits a phenotype that shares overlap with that of serpentine fibula-polycystic kidney syndrome and the autosomal dominant condition, Hajdu-Cheney syndrome. Here, we describe three individuals with these diagnoses. The individual with serpentine fibula-polycystic kidney syndrome, the fifth case reported in the literature, exhibited wormian bones which further expands the phenotypic spectrum for this condition and extends the overlap with Hajdu-Cheney syndrome. All three members of the filamin gene family, FLNA, and its functionally related paralogues, FLNB and FLNC, were screened for pathogenic mutations in all three individuals. We found a mutation in FLNA in the individual with Melnick-Needles syndrome, but no pathogenic variants in any filamin gene in the two individuals with Hajdu-Cheney syndrome and serpentine fibula-polycystic kidney syndrome. Clinical and molecular evidence indicates that Melnick-Needles syndrome is aetiologically distinct from Hajdu-Cheney syndrome and serpentine fibula-polycystic kidney syndrome, but these two latter conditions share many clinical similarities and may prove to be allelic to one another.

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Serpentine fibula syndrome: expansion of the phenotype with three affected siblings

Cited by 23 publications

References 0 publications

Serpentine fibula polycystic kidney syndrome is part of the phenotypic spectrum of Hajdu–Cheney syndrome

Serpentine fibula polycystic kidney syndrome is part of the phenotypic spectrum of Hajdu–Cheney syndrome

Syndromes and Diseases Associated with the Notch Signalling Pathway

Phenotypic overlap in Melnick–Needles, serpentine fibula–polycystic kidney and Hajdu–Cheney syndromes: a clinical and molecular study in three patients

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