Variable prenatal presentation of Pfeiffer syndrome: Suggested aids to prenatal sonographic diagnosis

Saliba, Souha; Morel, Baptiste; Gonzalès, Marie; Sénat, Marie-Victoire; Guilbaud, Lucie; Jouannic, Jean‐Marie; Cassart, Marie; Garel, Catherine; Blondiaux, Éléonore

doi:10.1002/pd.5231

Cited by 4 publications

(8 citation statements)

References 37 publications

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“…48 Moreover, the characteristic pattern of intracranial calcifications, osteosclerosis, and the lack of syndactyly and other digital anomalies differentiates RS from other craniosynostosis syndromes. 49 Fetal neuro-sonogram of all our cases showed a similar pattern of widespread intracranial calcifications mainly in the ventricular walls especially the occipital part, around the corpus callosum and in the basal ganglia. Moreover, in the third fetus, there was calcification in the cerebellum.…”

Section: Discussionsupporting

confidence: 64%

“…Additionally, the lack of relative macrocephaly, severe mesomelic shortening of the upper limbs, and genital anomalies excluded the diagnosis of the Robinow syndrome 48 . Moreover, the characteristic pattern of intracranial calcifications, osteosclerosis, and the lack of syndactyly and other digital anomalies differentiates RS from other craniosynostosis syndromes 49 …”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…15 Adding to craniosynostosis, principal ultrasound prenatal findings suggestive to PS are thumbs deformations and big toes. 7 Even when the cloverleaf skull is the most common finding in PS, and in our patient, it was the most important finding to perform PS diagnosis, the absence of this characteristic does not exclude the diagnosis, as well as its presence does not directly certify this syndrome, because other diseases can also present. 7 The presence of wide fingers, sacral appendix, vertebral fusions and coronal clefts in the prenatal ultrasound should lead the clinician to perform prenatal molecular tests to rule out PS.…”

Section: Discussionmentioning

confidence: 56%

“…PS low incidence and the wide variability of morphological findings, which can also be related to other conditions, makes it difficult to suspect this syndrome early pregnancy stages. 7 Pfeiffer syndrome is a clinically and autosomal dominant disorder caused by mutations in FGFR1 and FGFR2. 2 Only 17 cases of diagnosis in the prenatal stage have been reported in the world.…”

Section: Discussionmentioning

confidence: 99%

“… 7 The presence of wide fingers, sacral appendix, vertebral fusions and coronal clefts in the prenatal ultrasound should lead the clinician to perform prenatal molecular tests to rule out PS. 2 , 7 Almost all cases of PS are a consequence of new mutations because the parents are unaffected. Nevertheless, there is a percentage where the abnormal gene can be inherited from either parent.…”

Section: Discussionmentioning

confidence: 99%

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<p>Prenatal Diagnosis of Pfeiffer Syndrome Patient with FGFR2 C.940-1G>C Variant: A Case Report</p>

Torres‐Canchala

Castaño

Silva

et al. 2020

TACG

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Background: Pfeiffer syndrome (PS) is an autosomal dominant disorder caused by mutations in fibroblast growth factor receptor FGFR1 and FGFR2 genes, occurring in approximately 1:100,000 live births. PS has a wide range of clinical expression and severity, so early prenatal diagnosis is difficult and genetic counseling is desirable. We describe a PS newborn with her ultrasound and molecular studies. Case Report: We describe a female term newborn with cloverleaf-shaped skull, facial hypoplasia, low ears, exophthalmos and wide, broad and deviated thumbs and hallux. The patient was diagnosed by ultrasound at 29 WGA and referred to a tertiary care hospital for her follow-up. Molecular test revealed a heterozygous pathogenic variant in intron 8 of the FGFR2 gene (FGFR2: c.940-1G>C). It was a de-novo mutation. At 17 days of life, craniosynostosis correction and a Lefort-III frontomaxillary advancement were performed. Conclusion: Pfeiffer syndrome is a devastating genetic disorder. Prenatal diagnosis according PS morphological features in prenatal ultrasound allows timely genetic counseling, early referral to third-level centers, and close follow-up in the prenatal and postnatal stages.

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Prenatal diagnosis of Pfeiffer syndrome type 2 with increased nuchal translucency

Lin

Zhu

et al. 2021

Clinical Case Reports

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Variable prenatal presentation of Pfeiffer syndrome: Suggested aids to prenatal sonographic diagnosis

Abstract: Pfeiffer syndrome has a highly variable phenotype, and the absence of craniosynostosis on prenatal US does not exclude the diagnosis. Presence of abnormal thumbs and big toes, a sacral appendage, vertebral fusions, and coronal clefts should lead to prenatal molecular testing for PS.

Cited by 4 publications

References 37 publications

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

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

<p>Prenatal Diagnosis of Pfeiffer Syndrome Patient with FGFR2 C.940-1G>C Variant: A Case Report</p>

Prenatal diagnosis of Pfeiffer syndrome type 2 with increased nuchal translucency

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