Syndromic craniosynostoses usually occur as single gene disorders. In this study, we analyzed FGFR1-3 genes in four patients with Crouzon syndrome (CS), four patients with Pfeiffer syndrome type 2 (PS-2), one patient with Jackson-Weiss syndrome (JWS), and two patients (sisters) with Muenke syndrome (MS). FGFR2 and FGFR3 mutations were identified in 10 of the 11 patients. Notably, we found a novel FGFR2 p.Asn549Thr mutation in a patient with CS, and a novel FGFR2 p.Ser347Cys mutation in a patient with JWS (thus, this patient was turned out to have an FGFR2-related PS-variant). We also identified an FGFR2 p.Ser252Leu mutation in a phenotypically normal father of a daughter with CS, and an FGFR3 p.Pro250Arg mutation in a mildly macrocephalic father of sisters with MS. These findings, together with previous data, imply that the same FGFR2 mutations can be associated with a wide range of phenotypes including clinically different forms of syndromic craniosynostosis and apparently normal phenotype, depending on other (epi)genetic and environmental factors. Thus, genetic studies are recommended not only for obviously affected individuals but also for family members with apparently normal phenotype or non-specific subtle abnormal phenotype, to allow for pertinent genetic counseling. © 2016 Wiley Periodicals, Inc.

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Unilateral spatial neglect (USN) is a relatively common neurological disorder observed in patients after brain injury. Patients fail to attend to the contralesional side of space (1). Although USN is well documented in adults, it has been rarely reported in children (2-10). We present a child showing USN during an attack of hemiplegic migraine, without structural brain injury. The present report is the first in which USN during migraine is described.

Patient: Female, 4-year-old Final Diagnosis: Pfeiffer syndrome Symptoms: Craniosynostosis • tracheal cartilage sleeves Medication: — Clinical Procedure: — Specialty: Pathology • Pediatrics and Neonatology Objective: Rare disease Background: Pfeiffer syndrome (PS) is a fibroblast growth factor receptor ( FGFR )-associated craniosynostosis syndrome, characterized by abnormally broad and medially deviated thumbs and great toes. Tracheal cartilage sleeve (TCS) is associated with several FGFR -associated craniosynostosis syndromes, including PS. TCS is an airway malformation in which the tracheal cartilage rings fuse with each other to form a sleeve of cartilage. Case Report: The patient was a 4-year-old girl with PS, TCS, and abnormal hyperplasia of non-fused intrapulmonary cartilages. The patient showed cranial dysplasia on prenatal ultrasonography. At birth, a cloverleaf skull in association with hydrocephalus and digital malformations was apparent. These findings were consistent with PS type 2. The diagnosis of PS type 2 was confirmed from a genetic test detecting a FGFR2 mutation (Y340C). During the clinical course, she underwent several surgeries, including ventriculoperitoneal shunts, sequential cranioplasty surgeries, and tracheotomy due to upper airway abnormalities. At 4 years old, she died of multiple organ failure following aspiration pneumonia. The autopsy revealed that the tracheal cartilages had fused with each other, resulting in a condition called TCS, in which the cartilage rings and tracheal ligaments were absent. The lungs were poorly aerated, and the dilated bronchi had thickened walls surrounded by many cartilage fragments, mainly at the hilum. These cartilages tended to overlap at both ends, did not fuse, and were greatly altered in size and shape. Conclusions: We report the results of autopsy for PS with the first histopathological findings for the lungs and other visceral organs.