Raine syndrome: a review and a report of metabolic bone disease as a new link

Mahmood, Nasim

doi:10.13070/rs.en.1.890

Cited by 11 publications

(32 citation statements)

References 17 publications

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“…Here we showed that hydrocephalus was not congenital and triventricular, suggesting that underdeveloped posterior fossa led to obstruction of CSF circulation with age. Similar to our patient, previously reported cases with hydrocephalus required shunt operation at 6 to 8 months of age [27,28,33]. These cases were also most severely affected non-lethal RS cases with severe mental and motor delay [27,28] or lethal cases live long enough to develop hydrocephalus [33].…”

Section: Discussionsupporting

confidence: 88%

“…Similar to our patient, previously reported cases with hydrocephalus required shunt operation at 6 to 8 months of age [27,28,33]. These cases were also most severely affected non-lethal RS cases with severe mental and motor delay [27,28] or lethal cases live long enough to develop hydrocephalus [33]. Thus, it must be kept in mind that patients with RS can develop hydrocephalus with time and cranial imaging is required in case of neurological deterioration.…”

Section: Discussionsupporting

confidence: 86%

“…Table 2) [2,30,31,[36][37][38]. FGF23 levels could be studied in a few cases and shown to be elevated [4,5,28,39], but elevated urinary phosphate excretion had been shown in almost all cases including the case herein [24,27,28,34,39]. However, serum phosphate levels were found to be normal in some of the patients [4,20,[32][33][34][35].…”

Section: Discussionmentioning

confidence: 98%

“…Furthermore, our patient had optic atrophy with hypoplastic optic nerve, periventricular calcifications, corpus callosum hypoplasia, and hydrocephalus requiring shunt operation at nine months of age. Intracranial calcifications are commonly reported in RS [3]; however, hydrocephalus [27,28,33], optic atrophy [19], and corpus callosum dysgenesis [37] are reported rarely. Here we showed that hydrocephalus was not congenital and triventricular, suggesting that underdeveloped posterior fossa led to obstruction of CSF circulation with age.…”

Section: Discussionmentioning

confidence: 99%

“…Fradin et al [20] reported generalized osteosclerosis at birth which decreased with age, and the patient had normal appearing bones with distinct corticomedullary differentiation and normal cortical thickness at 3 years of age. Additionally, RS cases presenting in older ages had preserved corticomedullary junction or only focal sclerosis and mildly increased bone mineral density [5,20,24,28,37,39]. Therefore, it seems that osteosclerosis and especially periosteal bone formation is related to the severity of the RS.…”

Section: Discussionmentioning

confidence: 99%

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A Rare Cause of Hypophosphatemia: Raine Syndrome Changing Clinical Features with Age

et al. 2020

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Raine Syndrome (RS) is caused by biallelic loss-of-function mutations in FAM20C gene and characterized by hypophosphatemia, typical facial and skeletal features. Subperiosteal bone formation and generalized osteosclerosis are the most common radiological findings. Here we present a new case with RS. A 9-month-old male patient on a home-type ventilator was referred for hypophosphatemia. He was born with a weight of 3800 g to non-consanguineous parents. Prenatal ultrasound had demonstrated nasal bone agenesis. A large anterior fontanel, frontal bossing, exophthalmos, hypoplastic nose, high arched palate, low set ears, triangular mouth, and corneal opacification were detected on physical examination. Serial skeletal X-rays revealed diffuse osteosclerosis at birth which was gradually decreased by the age of 5 months with subperiosteal undermineralized bone formation and medullary space of long bone could be distinguishable with bone-within-abone appearance. At 9 months of age, hand X-ray revealed cupping of the ulna with loose radial bone margin with minimal fraying and osteopenia. Cranial computed tomography scan showed bilateral periventricular calcification and hydrocephalus in progress. The clinical, laboratory, and radiological examinations were consistent with RS. Molecular analyses revealed a compound heterozygous mutation in FAM20C gene (a known pathogenic mutation, c.1645C > T, p.Arg549Trp; and a novel c.863 + 5 G > C variant). The patient died due to respiratory failure at 17 months of age. This case allowed us to demonstrate natural progression of skeletal features in RS. Furthermore, we have described a novel FAM20C variant causing RS. Previous literature on RS is also reviewed.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A Rare Cause of Hypophosphatemia: Raine Syndrome Changing Clinical Features with Age

et al. 2020

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Fetal ultrasonographic findings including cerebral hyperechogenicity in a patient with non‐lethal form of Raine syndrome

Tamai

Tada

Takeuchi

et al. 2018

American J of Med Genetics Pt A

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Raine syndrome is a rare osteosclerotic bone dysplasia characterized by craniofacial anomalies and intracranial calcification. Most patients with Raine syndrome are of Arab ancestry and die during the neonatal period. We herein report a Japanese patient with non-lethal Raine syndrome who presented with characteristic cerebral hyperechogenicity and a hypoplastic nose by fetal ultrasonography. She was admitted to the NICU due to pyriform aperture stenosis. Craniofacial abnormalities, intracranial calcification, osteosclerosis, chondrodysplasia punctata, and a mutation of FAM20C was identified. She was subsequently discharged without surgical intervention and is now 2 years old with mild neurodevelopmental delays. Images of cerebral hyperechogenicity by fetal ultrasonography in a non-lethal case were described herein for the first time. This patient represents a rare occurrence of a child with Raine syndrome born to Japanese parents and confirms that this syndrome is not always lethal. Even if Raine syndrome is suspected in a fetus due to cerebral hyperechogenicity and a hypoplastic nose, cerebral hyperechogenicity without pulmonary hypoplasia does not always predict lethality or severe neurodevelopmental delays. The information provided herein will be useful for prenatal counseling.

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A novel FAM20C mutation causes a rare form of neonatal lethal Raine syndrome

Hung

Rodrı́guez

Roberts

et al. 2019

American J of Med Genetics Pt A

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Raine syndrome is a rare, autosomal recessive, osteosclerotic bone dysplasia due to pathogenic variants in FAM20C. The clinical phenotype is characterized by generalized osteosclerosis affecting all bones, cerebral calcifications, and craniofacial dysmorphism.Most cases present during the neonatal period with early lethality due to pulmonary hypoplasia and respiratory compromise while only few affected individuals have been reported to survive into adulthood. FAM20C is a ubiquitously expressed protein kinase that contains five functional domains including a catalytic domain, a binding pocket for FAM20A and three distinct N-glycosylation sites. We report a newborn infant with a history of prenatal onset fractures, generalized osteosclerosis, and craniofacial dysmorphism and early lethality. The clinical presentation was highly suggestive of Raine syndrome. A homozygous, novel missense variant in exon 5 of FAM20C (c.1007T>G; p. Met336Arg) was identified by targeted Sanger sequencing. Following in silico analysis and mapping of the variant on a three-dimensional (3D) model of FAM20C it is predicted to be deleterious and to affect N-glycosylation, protein folding, and subsequent secretion of FAM20C. In addition, we reviewed all published FAM20C mutations and observed that most pathogenic variants affect functional regions within the protein establishing evidence for an emerging genotype-phenotype correlation. K E Y W O R D S FAM20C, osteosclerosis, Raine syndrome

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Raine syndrome: a review and a report of metabolic bone disease as a new link

Cited by 11 publications

References 17 publications

A Rare Cause of Hypophosphatemia: Raine Syndrome Changing Clinical Features with Age

A Rare Cause of Hypophosphatemia: Raine Syndrome Changing Clinical Features with Age

Fetal ultrasonographic findings including cerebral hyperechogenicity in a patient with non‐lethal form of Raine syndrome

A novel FAM20C mutation causes a rare form of neonatal lethal Raine syndrome

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