This study reevaluates a surgical technique known as the Chula technique, previously reported in 1991 for correction of frontoethmoidal encephalomeningocele. From 1986 to 1999, 108 patients were operated on with this technique, which could remove the herniation mass, repair dural and bone defects, reconstruct the naso-orbital area, and restore aesthetic facial appearance in a single stage. Formal frontal craniotomy was not necessary. The result has been very satisfying in terms of safety, cure rate, and aesthetic outcome. Spontaneous improvement of lacrimal passage obstruction occurred in 85.2 percent of cases, and dacryocystorhinostomy was required in the rest. There was no mortality. Complications (e.g., wound infection, 6.5 percent; wire extrusion, 3.7 percent; meningitis, 2.8 percent; cerebrospinal fluid leakage, 2.8 percent; and postoperative increased intracranial pressure, 2.8 percent) were much less frequent than in other reports. With a mean follow-up period of 439 days (maximum, 12 years), there has been no recurrence.

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Mutations in the fibroblast growth factor receptor genes (FGFR) have been known to be associated with many craniosynostosis syndromes with overlapping phenotypes. We studied a 15-year-old Thai boy with an unspecified craniosynostosis syndrome characterized by multiple suture craniosynostoses, a persistent anterior fontanel, corneal scleralization, choanal stenosis, atresia of the auditory meatus, broad thumbs and great toes, severe scoliosis, acanthosis nigricans, hydrocephalus, and mental retardation. Radiography revealed bony ankyloses of vertebral bodies of T9-12, humero-radio-ulnar joints, intercarpal joints, distal interphalangeal joints of fifth fingers, fibulo-tibial joints, intertarsal joints, and distal interphalangeal joints of the first toes. The patient was a heterozygous for a 870G --> T change resulting in a W290C amino acid substitution in the extracellular domain of the fibroblast growth factor receptor 2 gene (FGFR2). This mutation has previously been reported in a patient with severe Pfeiffer syndrome type 2 that is distinct from the craniosynostosis in our patient. These findings emphasize locus, allelic, and phenotypic heterogeneity of craniofacial-skeletal-dermatological syndrome due to FGFR2 mutations.

Pfeiffer syndrome (PS) (MIM 101600) is one of the most common syndromic forms of craniosynostosis. It is characterized by craniosysnostosis, midface hypoplasia, broad and medially deviated thumbs, and great toes with partial syndactyly of the digits. Here, we described clinical and genetic features of 12 unrelated Thai individuals with PS. All 12 patients were sporadic, and advanced paternal age was found in 50% of the cases. Polymerase chain reaction sequencing of FGFR1 exon 5 and FGFR2 exons 8, 10, 15, 16, and 17 was performed in all PS patients and revealed 9 recurrent mutations in all patients. Most of the mutations clustered in exons 8 and 10 (9/12) accounting for 75% of PS cases. The most frequently detected mutation, p.S351C, was associated with the severe form of PS in the Thai population. Less frequent mutations in exons 16 (p.K641R) and 17 (p.G663E) were also identified. In addition, the p.P252R mutation in FGFR1 was detected in 1 PS patient with unilateral coronal craniosynostosis expanding the phenotypic spectrum of PS with this particular mutation. Knowing the mutation spectrum of the responsible genes could lead to the most effective strategy in identifying mutations causing Pfeiffer syndrome in the Thai population.

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Crouzon and Apert syndromes have been reported to be associated with mutations in Fibroblast Growth Factor Receptor 2 (FGFR2) gene in various ethnic groups, but never in Southeast Asian subjects. Therefore, the authors conducted a study to characterize 11 Thai patients: four with Crouzon syndrome and seven with Apert syndrome. All cases are sporadic. Mean paternal and maternal ages were 38.7 and 28.6 years, respectively. Molecularly, all patients were found to have mutations in the FGFR2 gene. Three mutations (C278F, S347C, S351C) were detected in all Crouzon patients with two having S351C. The seven patients with Apert syndrome have either S252W or P253R mutation. The authors' findings that sporadic cases were associated with advanced paternal age and that they all had mutations in FGFR2 are consistent with previous reports. This is another observation supporting the causative role of FGFR2 mutations in Crouzon and Apert syndromes.

Van der Woude syndrome (VWS) is a dominantly inherited disorder characterized by cleft lip with or without cleft palate and lip pits. It remains the most common syndromic form of oral clefts. Mutations in the interferon regulatory factor 6 (IRF6) gene have been identified in patients with VWS. We reported three unrelated families with lower lip anomalies. Two had lower lip pits, a cardinal sign of VWS, but the other had a heart-shaped mass on lower lip without pits, oral clefts, or hypodontia. This isolated anomaly has not been previously observed in VWS. We performed mutation analysis by PCR-sequencing the entire coding region of the IRF6 gene. Three potentially pathogenic mutations, c.145C>T (p.Q49X), c.171T>G (p.F57L), and 1306C>G (p.L436V) were successfully identified. All the missense mutations were not detected in 100 unaffected ethnic-matched control chromosomes and have never been previously reported. The p.Q49X and p.F57L mutations were located in the highly conserved DNA binding domain while the p.L436V was located at the carboxy-terminal region. This study reported an undescribed clinical feature of VWS and three novel mutations, expanding the phenotypic spectrum of VWS and mutational spectrum of IRF6.