Non-lethal Raine Syndrome in a Middle-Aged Woman Caused by a Novel FAM20C Mutation

Mamedova, Elizaveta; Dimitrova, Diana; Przhiyalkovskaya, Elena; Buryakina, Svetlana; Vasilyev, Evgeny; Tiulpakov, Anatoly; Belaya, Zhanna

doi:10.1007/s00223-019-00599-w

Cited by 16 publications

(23 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Overall, we present follow-up data of non-lethal RS in the single largest cohort of patients and with the longest follow up duration, the oldest of our patients being 18 years old at present. We, therefore, can support the previous data that life expectancy for these patients goes beyond childhood [19][20][21][22]. We found great heterogeneity in terms of the rate of complications emerging during follow-up.…”

Section: Discussionsupporting

confidence: 88%

“…The main epidemiological characteristics of our patients at diagnosis do not differ from the previous descriptions reported in the literature; all children were born to consanguinous parents, more frequently of Asian ethnicity. This report, with the addition of three new cases, confirmed that most cases were not Caucasian which is likely to be related to the lower prevalence of consanguinity in this population [1,19].…”

Section: Discussionsupporting

confidence: 65%

See 1 more Smart Citation

Natural history of non-lethal Raine syndrome during childhood

Mameli

Zichichi

Mahmood

et al. 2020

Orphanet J Rare Dis

View full text Add to dashboard Cite

Background: Raine syndrome (RS) is a rare autosomal recessive disorder caused by biallelic loss-of-function mutations of FAM20C. The most common clinical features are microcephaly, exophthalmos, hypoplastic nose and severe midface hypoplasia, leading to choanal atresia. The radiological findings include generalized osteosclerosis and brain calcifications. RS is usually lethal during the neonatal period due to severe respiratory distress. However, there exists a non-lethal RS form, the phenotype of which is extremely heterogeneous. There is paucity of data about clinical course and life expectancy of these patients. Results: This is the first description of follow-up features of non-lethal RS patients. Moreover, we present three unpublished cases. There are five Asian and two Arab patients. All were born to consanguineous parents. The most common neonatal comorbidity was respiratory distress secondary to choanal atresia. A variable degree of neurodevelopmental delay was seen in the majority of our cases and seizures and hearing or vision involvement were also frequent. Neurological and orthopedic issues were the most frequent complications seen at follow-up in our group. Persistent hypophosphatemic rickets was the most striking endocrinological manifestation, which was scarcely responsive to therapy with phosphate salts and alfacalcidol. Life expectancy of our patients goes beyond childhood, with the oldest of those described being 18 years old at present. Conclusions: Manifestations of RS in those surviving the neonatal period are being increasingly recognized. Our study supports previous findings and provides clinical and biochemical observations and data from longer follow up. Finally, we propose multidisciplinary follow up for patients with non-lethal RS.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 65%

Natural history of non-lethal Raine syndrome during childhood

Mameli

Zichichi

Mahmood

et al. 2020

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…Nephrocalcinosis is not examined in most of the cases; however, 6 cases with nephrocalcinosis including the case reported herein were identified. Ectopic soft tissue calcifications and calcification in different organ systems such as ovaries, liver, and spleen have been also reported in RS [20,21,25]. It seems that intracranial calcification is a consistent feature of the disease and independent from serum calcium and phosphate, as it has been described at birth and/ or antenatal USG [2,31,38].…”

Section: Discussionmentioning

confidence: 79%

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

“…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%

Two Novel FAM20C Variants in a Family with Raine Syndrome

Hernández-Zavala

Cortés-Camacho

Palma‐Lara

et al. 2020

Genes

View full text Add to dashboard Cite

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.

show abstract

Non-lethal Raine Syndrome in a Middle-Aged Woman Caused by a Novel FAM20C Mutation

Cited by 16 publications

References 17 publications

Natural history of non-lethal Raine syndrome during childhood

Natural history of non-lethal Raine syndrome during childhood

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

Two Novel FAM20C Variants in a Family with Raine Syndrome

Contact Info

Product

Resources

About