Feeding, Communication, Hydrocephalus, and Intracranial Hypertension in Patients With Severe FGFR2-Associated Pfeiffer Syndrome

Abstract

Background: Pfeiffer syndrome is associated with a genetic mutation of the FGFR2 (or more rarely, FGFR1) gene, and features the combination of craniosynostosis, midface hypoplasia, broad thumbs and broad great toes. Previous research has identified a wide spectrum of clinical phenotypes in patients with Pfeiffer syndrome. This study aimed to investigate the multifactorial considerations for speech, language, hearing and feeding development in patients with severe geneticallyconfirmed Pfeiffer syndrome.Methods: A 23-year retrospective case-note review of patients attending the Oxford Craniofacial Unit was undertaken. Patients were categorized according to genotype. Patients with mutations located in FGFR1, or outside the FGFR2 IgIII domainhotspot, or representing known Crouzon/Pfeiffer overlap substitutions were excluded. Twelve patients with severe FGFR2-associated Pfeiffer syndrome were identified.Results: Patients most commonly had pansynostosis (n=8) followed by bicoronal (n=3), and bicoronal and sagittal synostosis (n=1). Seven patients had a Chiari I malformation. Four patients had a diagnosis of epilepsy. Ten patients had with hydrocephalus necessitating ventriculoperitoneal shunt insertion.Feeding difficulties were common (n=10/12) and multifactorial. In 5/12 cases, they were associated with pansynostosis, hydrocephalus, tracheostomy and tube feeding in infancy.Hearing data were available for 10 patients, of whom 9 had conductive hearing loss, and 8 required hearing aids. Results indicated that 3/4 patients had expressive language difficulties, 3/4 had appropriate receptive language skills. 6/12 patients had a speech sound disorder and abnormal resonance. Conclusion:This study has identified important speech, language, hearing and feeding issues in patients with severe FGFR2-associated Pfeiffer syndrome. Results indicate that a high rate of motor-based oral stage feeding difficulties, and pharyngeal stage swallowing difficulties necessitating regular review by specialist craniofacial speech and language therapists

What We Know About Intracranial Hypertension in Children With Syndromic Craniosynostosis

“…Of the 28 studies, 17 studies relied on invasive ICP measurements or LP alone to assess ICH. 2,3,[5][6][7][8]18,[20][21][22]24,77,[84][85][86][87]92 A further 11 studies also used indirect methods of ICH assessment in addition to the invasive ICP or LP measurement. [9][10][11][12][13][14][15][16][17]19,23 Twenty-five studies used ICP, 3,[5][6][7][8]18,21,22,24,77,[84][85][86][87]89,93 one study used LP, 18 and 2 used ICP and LP 16,23 to determine ICH.…”

“…2,3,[5][6][7][8]18,[20][21][22]24,77,[84][85][86][87]92 A further 11 studies also used indirect methods of ICH assessment in addition to the invasive ICP or LP measurement. [9][10][11][12][13][14][15][16][17]19,23 Twenty-five studies used ICP, 3,[5][6][7][8]18,21,22,24,77,[84][85][86][87]89,93 one study used LP, 18 and 2 used ICP and LP 16,23 to determine ICH. Of the 25 studies using ICP, 21 reports both the duration and cut-off value.…”

“…Of the 25 studies using ICP, 21 reports both the duration and cut-off value. 2,3,[5][6][7][8][10][11][12][13][14][15]21,22,24,77,[84][85][86][87]89 Of the remaining 4, 1 reports duration but does not report cutoff value, 9 and 3 reports neither duration nor cut-off values used to determine ICH. 17,19,20 In the 3 LP measurement studies, 1 reported duration and cutoff value, 18 1 used the CSF opening pressure for LP measurement, reports cutoff value but not duration of ICP measurement, 16 and the last did not report duration or cutoff values for ICP and LP measurement.…”

“…Twenty-two studies described the duration of ICP measurement used to determine the presence of ICH. 2,3,[5][6][7][8][9][10][11][12][13][14][15]22,24,77,[84][85][86][87]89,94 Ten studies used 24 hours of data, 3,[9][10][11][12][13][14][15]24,87 6 used overnight measurements, 2,[5][6][7][8]84 and 4 studies used 1 minute of ICP measurements during anesthesia providing the ICP waveform was stable. 21,22,85,86 Two studies used another duration: 1 study used while under anesthesia for the length of surgical procedures, 77 and 1 for 48 hours.…”

“…2,3,5,7,8,10,16,21,22,77,[84][85][86] One study used threshold value of 20 mm Hg to determine ICH. 89 In the 8 other studies, a stricter definition of ICH was used: > 15 mm Hg as well as presence of ≥ 3 ICP B-waves in 24 hours, 24,87 or plateau waves rising ≥ 35 mm Hg and lasting ≥ 20 minutes. [11][12][13][14][15] One study also applied age-related cutoff values, that is, > 2 mm Hg for neonates, > 13 mm Hg for children 1 to 7 years, and > 15 mmHg for children ≥ 7 years old.…”