Raine syndrome

Vishwanath, B. T; Srinivasa, K; Shankar, M. Veera

doi:10.4103/0971-6866.132761

Cited by 9 publications

(12 citation statements)

References 6 publications

(8 reference statements)

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“…All individuals affected with lethal RS survive hours, days or weeks, with death mainly resulting from respiratory failure. In 2009 two unrelated individuals of 8 and 11 years were reported with non-lethal Raine syndrome, and to date, 22 cases have been described [3][4][5]10,[23][24][25][26][27][28][29][30][31][32][33]. Thus, two types of RS are recognized: lethal and non-lethal RS.…”

Section: Discussionmentioning

confidence: 99%

“…Prior to 2009, only lethal cases of RS had been described with the typical RS phenotype. The first non-lethal (NLRS) cases were described in 2009 [23], with new cases found in adolescents and adults with a wide variable expression [23][24][25][26][27][28][29][30][31][32][33] The major NLRS features are: hypoplastic nose, amelogenesis imperfecta, hearing defects, ectopic calcifications, osteonecrosis, and intellectual disability [3][4][5]10,[23][24][25][26][27][28][29][30][31][32][33]. Most cases of lethal RS (LRS) are detected at birth, which present major features including facial alterations such as flat facial profile, hypoplastic nose, and prominent eyes, in addition to mineralization defects like osteosclerotic bone defects and vascular and brain calcification, as well as respiratory defects like choanal atresia/stenosis and lung hypoplasia [6][7][8][9][10][11][34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

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Two Novel FAM20C Variants in a Family with Raine Syndrome

Hernández-Zavala

Cortés-Camacho

Palma‐Lara

et al. 2020

Genes

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Two siblings from a Mexican family who carried lethal Raine syndrome are presented. A newborn term male (case 1) and his 21 gestational week brother (case 2), with a similar osteosclerotic pattern: generalized osteosclerosis, which is more evident in facial bones and cranial base. Prenatal findings at 21 weeks and histopathological features for case 2 are described. A novel combination of biallelic FAM20C pathogenic variants were detected, a maternal cytosine duplication at position 456 and a paternal deletion of a cytosine in position 474 in exon 1, which change the reading frame with a premature termination at codon 207 and 185 respectively. These changes are in concordance with a negative detection of the protein in liver and kidney as shown in case 2. Necropsy showed absence of pancreatic Langerhans Islets, which are reported here for the first time. Corpus callosum absence is added to the few reported cases of brain defects in Raine syndrome. This report shows two new FAM20C variants not described previously, and negative protein detection in the liver and the kidney. We highlight that lethal Raine syndrome is well defined as early as 21 weeks, including mineralization defects and craniofacial features. Pancreas and brain defects found here in FAM20C deficiency extend the functional spectrum of this protein to previously unknown organs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Two Novel FAM20C Variants in a Family with Raine Syndrome

Hernández-Zavala

Cortés-Camacho

Palma‐Lara

et al. 2020

Genes

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“…In comparison, the clinical features of milder form showed microcephaly, delayed language and fine motor skills, periapical abscesses, gingival hyperplasia, and open bite malocclusion, confirming the clinical heterogeneity of this disorder and the presence of a continuous phenotypic spectrum 8‐20 …”

Section: Introductionmentioning

confidence: 75%

“…5,9,23,38,41 Thirty-five lethal cases (including this report) 1,3,5-7,21-41 and 22 non-lethal cases with significant variability in the severity have been reported. [8][9][10][11][12][13][14][15][16][17][18][19][20] In our series, we highlight our experience with the prenatal detection of three lethal RS that was suspected as early as the 22 weeks of gestation following the detection of the characteristic craniofacial dysmorphic features, osteosclerosis, and ectopic calcification in the brain and other organs.…”

Section: Discussionmentioning

confidence: 91%

“…1,3,[5][6][7] In comparison, the clinical features of milder form showed microcephaly, delayed language and fine motor skills, periapical abscesses, gingival hyperplasia, and open bite malocclusion, confirming the clinical heterogeneity of this disorder and the presence of a continuous phenotypic spectrum. [8][9][10][11][12][13][14][15][16][17][18][19][20] No specific prenatal ultrasound findings have been reported in RS. Our report highlights the fetal phenotype in three cases with lethal RS which includes distinguished pattern of intracranial calcification and fetal facial phenotype.…”

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Raine syndrome: Prenatal diagnosis based on recognizable fetal facial features and characteristic intracranial calcification

et al. 2020

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Objective: The purpose of this study was to elucidate the facial morphology and the pattern of internal malformations in three fetuses with RS born to first cousins of Egyptian decent. Methods: The fetal ultrasonography findings were highly suggestive of RS leading to targeted Sanger sequencing of FAM20C and postnatal assessment. Results: The prenatal ultrasound findings of osteosclerotic skull, exorbitism, hypoplastic nose, midface hypoplasia, small mouth with down-curved corners, and a distinct and recognizable pattern of intracranial calcification were identified in three fetuses with RS. The calcifications were evident specifically around the corpus callosum and/or ventricular walls. Ectopic renal and hepatic calcifications, pulmonary hypoplasia, mild rhizomelic shortening of the upper limbs, intrauterine fractures, and cerebellar hypoplasia were also noted. Molecular analysis identified three novel homozygous variants, two frameshift: [c.456delC (p.Gly153Alafs*34)] in exon 1 and [c.905delT (Phe302Serfs*35)] in exon 4 and one nonsense mutation in exon 10, [c.1557C>G(p.Tyrs519*)]. The three variants were segregated with the phenotype. This is the first description of a phenotype associated with homozygous truncating variants of FAM20C. Conclusion: RS has characteristic prenatal ultrasound findings which can improve the prenatal identification of this condition and help in guiding the molecular diagnosis and counseling. 1 | INTRODUCTION Raine syndrome (RS) (OMIM # 259775) is characterized by the combination of generalized osteosclerosis with periosteal bone formation, characteristic dysmorphic facial features, and intracerebral calcification. 1-4 It was initially described as an early neonatal lethal disorder with early onset that usually results in death within the first few days of life. 5-7 In 2009, non-lethal RS cases were described and subsequently new cases were found in adolescents and adults with significant variability in the severity of this condition, thus expanding our knowledge of the prognosis and long-term manifestations of this condition. 8-20 Periosteal bone formation is a cornerstone feature of this disorder and differentiates it from osteopetrosis and other known lethal and nonlethal osteosclerotic bone dysplasias. 3,8 The periosteal bone formation typically extends along the diaphysis of long bones adjacent to areas of cellular soft tissue. 8 Ectopic mineralization has been reported at different sites including the brain and kidneys in both lethal and non-lethal cases. 9,14,21-23 Preferential sites of calcification were the basal ganglia, the corpus callosum, and the frontal lobes. 5,17,22 In lethal type, the cause of death in all patients was the respiratory failure, with survival time varying from 45 minutes to 8 weeks in

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