Jyri Hukki

Auditory ERPs reveal brain dysfunction in infants with plagiocephaly.

It is suspected that the developmental delay in school-aged children diagnosed as infants suffering from plagiocephaly is caused by the modification of the skull form. To detect possible cognitive impairment in these children, we examined auditory ERPs to tones in infant patients. The infants with plagiocephaly exhibited smaller amplitudes of the P150 and the N250 responses to tones than healthy controls. Differences between the patients and control subjects indicate that already at this early age the presence of the plagiocephalic skull signals compromise of brain functioning. The present data suggest that most of the plagiocephalic infants have an elevated risk of auditory processing disorders. In the current study we demonstrated, for the first time, that the central sound processing, as reflected by ERPs, is affected in children with plagiocephaly.

Collagen XI sequence variations in nonsyndromic cleft palate, Robin sequence and micrognathia

Cleft palate is a common birth defect, but its etiopathogenesis is mostly unknown. Several studies have shown that cleft palate has a strong genetic component. Robin sequence consists of three of the following four findings: micrognathia, glossoptosis, obstructive apnea, and cleft palate. While cleft palate is mainly nonsyndromic, about 80 percent of Robin sequence cases are associated with syndromes. Mutations in genes coding for cartilage collagens II and XI, COL2A1, COL11A1 and COL11A2, have been shown to cause chondrodysplasias that are commonly associated with Robin sequence, micrognathia or cleft palate. We therefore analyzed a cohort of 24 patients with nonsyndromic Robin sequence, 17 with nonsyndromic cleft palate and 21 with nonsyndromic micrognathia for mutations in COL11A2. A total of 23 Robin sequence patients were also analyzed for mutations in COL2A1 and COL11A1. We detected two disease-associated mutations in patients with Robin sequence, an Arg to stop codon mutation in COL11A2 and a splicing mutation in COL11A1. Two putatively disease-associated sequence variations were found in COL11A1 in Robin sequence patients, one in COL11A2 in a patient with micrognathia and one in COL2A1 in two patients with Robin sequence. The results showed that sequence variations in these genes can play a role in the etiology of Robin sequence, cleft palate and micrognathia but are not common causes of these phenotypes.

Dysfunction of the auditory cortex persists in infants with certain cleft types

Language and learning disabilities occur in almost half of individuals with oral clefts. The characteristics of these cognitive dysfunctions vary according to the cleft type, and the mechanisms underlying the relation between cleft type, cognitive dysfunction, and cleft‐caused middle‐ear disease are unknown. This study investigates preattentive auditory discrimination, which plays a significant role in language acquisition and usage, in infants with different cleft types. A mismatch negativity (MMN) component of brain evoked potentials, which indexes preconscious sound discrimination, and brain responses to rare sine‐wave tones were recorded in 12 healthy infants and 32 infants with oral clefts at the ages of 0 and 6 months. Infants with clefts were subdivided into two categories: those with cleft lip and palate (CLP) (n=11 at birth, n=6 at the age of 6 months) and those with cleft palate only (CPO) (n=17 at birth, n=8 at the age of 6 months). At both ages, brain responses to rare sounds tended to be smaller in both cleft subgroups than in healthy peers. However, in the latency range of 300 to 500 ms, the MMN was significantly smaller in infants with CPO. In infants with CLP, the MMN was comparable to that of healthy infants. Differences in auditory discrimination between infants with CLP and CPO, as reflected by MMN, were detectable at birth and persisted into later infancy. This pattern parallels known behavioural differences between children with these cleft types. Brain responses to rare sounds, in contrast, had no differentiative power with respect to the cleft type.

The first neurophysiological evidence for cognitive brain dysfunctions in children with Catch

CATCH syndrome, caused by a microdelection in chromosome 22, is characterized by cleft palate and cardiac anomalies. The majority of these children also have learning difficulties or speech and language deficits. These problems are often due to the dysmorphology of the articulatory system. In the present study, the duration of auditory sensory memory, which is of central importance to speech perception and understanding, was investigated. As a research method we used mismatch negativity (MMN), an attention independent eventrelated potential, which provides an objective electrical index of auditory sensory memory. The present data suggest that the duration of this memory span is considerably shorter in 6–10-year-old children with CATCH than in healthy controls. Thus, the language-related problems encountered in children suffering from CATCH syndrome are likely to be caused also by CNS dysfunctions.

Cortical auditory dysfunction in children with oral clefts: relation with cleft type

OBJECTIVE Up to 46% of individuals with oral clefts suffer from language-learning disabilities. The degree of these disabilities varies according to cleft type. The pathogenesis of cognitive malfunctioning or its relationship with cleft type is not known. We investigated persistence of auditory short-term memory (STM) that is implicitly involved in language-specific perception in children with clefts, grouped using fine-graded cleft classification. METHODS Cortical evoked potentials were recorded in 78 children with non-syndromic oral clefts and in 32 healthy peers. A mismatch negativity (MMN) potential that indexes preattentive detection of change in auditory input was obtained in response to tone sounds. In order to test durability of short-term memory traces, sounds were presented with three stimulation rates. RESULTS With slowest stimulation, MMN amplitudes were reduced in cleft children as compared to the healthy peers (P < 0.00065). Only cleft-lip children did not significantly differ from controls. Among isolated palatal clefts, the more posteriorly delimited the cleft was, the smaller was the amplitude of MMN. MMNs of smallest amplitudes were obtained in the subgroup of complete unilateral cleft of lip and palate. CONCLUSIONS Reduced MMN amplitudes, found in cleft children, imply deficiency in auditory STM trace maintenance. This dysfunction is likely to contribute to their language and learning disabilities. The MMN diminution with shorter/more posterior clefts suggests that differences in auditory cortex function are one of the underlying mechanisms of the cleft type-malcogniton association.

Brain dysfunction in neonates with cleft palate revealed by the mismatch negativity.

OBJECTIVES Our recent studies have demonstrated that the brains automatic change-detection response, the mismatch negativity (MMN) of the event-related brain potential (ERP), is significantly attenuated in school-age children with CATCH syndrome and in children of the same age with cleft palate but without the CATCH syndrome. Among other problems, various kinds of learning difficulties are commonly reported in these patient groups. The present study aimed at investigating whether the MMN is attenuated already in newborns with cleft palate compared with healthy controls. METHODS Stimuli of 1000 Hz were presented frequently and 1100 Hz infrequently to 9 neonates with cleft palate and to 8 healthy controls. Infrequent 1100 Hz stimuli elicited a prominent MMN in all of the healthy children, but only in 3 of the 9 infants with cleft palate. RESULTS A significant difference in the mean amplitudes of responses to deviant tones between the healthy and cleft palate neonates was found. CONCLUSIONS MMN may indicate brain dysfunctions long before they have manifested themselves in cognitive disabilities, which would enable one to identify the infants with an elevated risk and to start their rehabilitation much earlier than before.

Mismatch negativity (mmn) as an index of auditory sensory memory deficit in cleft-palate and Catch syndrome children

OUR recent study demonstrated with the brains automatic change-detection response, the mismatch negativity (MMN) of the event-related potentials (ERPs), that the duration of auditory sensory memory is significantly shorter in school-age children with CATCH syndrome than in healthy age-matched controls. One of the haracteristic symptoms of this syndrome, caused by a microdelection in chromosome 22, is cleft palate. The most common problems in these children, however, are learning difficulties and, according to our results, it is likely that these problems are not due to the dysmorphology of peripheral speech mechanisms only but are also caused by CNS dysfunctions. In the present study we show with MMN that auditory sensory memory is also shortened in school-age children with cleft palate but without the ATCH syndrome. It has been shown in previous studies with neuropsychological tests that although children with cleft palate have language and learning-related problems these difficulties are usually less severe than those of CATCH children. Likewise the present study demonstrates that the auditory sensory memory trace seems to decay more rapidly in CATCH children than in children with cleft palate.

Five-Year Follow-Up of Maxillary Distraction Osteogenesis on the Dentofacial Structures of Children With Cleft Lip and Palate

PURPOSE To determine the long-term outcomes of maxillary distraction osteogenesis (DO) on skeletal and dental structures of growing children with cleft lip and palate. PATIENTS AND METHODS Severe maxillary deficiencies were treated with a rigid external distractor device followed by a consolidation period. Preoperative and postoperative orthodontic treatment lasted a mean of 14 months and 16 months, respectively. The landmarks on standard lateral cephalometric x-rays were digitized and angular and linear measurements were compared by Students t test to assess the changes before distraction, after distraction, after consolidation, at 1-year follow-up, and at 2-year follow-up. Long-term follow-up (5 years) was interpreted according to mean values because of the small sample size. RESULTS During DO, the maxilla was horizontally advanced and moved downward as indicated by the significant changes at the SNA and ANB angles (13 degrees) and at maxillary points A, ANS, and PNS. The increase at the divergence between the maxilla and mandible (ANS-PNS/Me-Go) was found to be significant. The mandible (B, Pg, Me) also moved downward (2-4 mm) and backward (Gn) significantly because of mandibular autorotation. The overjet increased (mean increase, 13.7 mm) and the overbite decreased significantly. The advancement of the upper incisors (13.3 mm) and upper molars (12.3 mm) was slightly more than the skeletal points. In a long-term follow-up (5 years), the ANB angle and horizontal overjet continued to decrease but both values remained positive, indicating a Class I relationship. CONCLUSIONS This cephalometric study of young adolescents with cleft lips and palates found great improvement in dentofacial structure after maxillary DO and stability in maxillary skeletal advancement. During a 5-year follow-up, the achieved dentoskeletal treatment outcome was partly diminished. The extreme need for maxillary advancement or facial correction because of psychosocial stress and providing an easier approach for finalizing osteotomy are the major 2 indications for DO treatment.

Five year follow-up of mandibular distraction osteogenesis on the dentofacial structures of syndromic children

OBJECTIVES To determine long-term treatment outcomes of mandibular distraction osteogenesis (DO) in syndromic children with severely hypoplastic lower jaws. DESIGN Descriptive clinical study. SETTING AND SAMPLE POPULATION Cleft Palate and Craniofacial Centre, Department of Plastic Surgery, Helsinki University Central Hospital. Ten children (mean age 7.6 years) with various syndromes (craniofacial microsomia, Treacher Collins syndrome, Nager syndrome). SUBJECTS AND METHODS Ten growing children with severely retrognathic lower jaws were distracted with an extraoral bicortically fixed DO device (mean, 34 days) followed by a consolidation period (mean, 9 weeks). Orthodontic treatment was performed pre- and/or postoperatively with fixed or functional appliances (mean 14 months). OUTCOME MEASURE The landmarks on standard lateral cephalometric X-rays were digitized and angular and linear measurements were compared using Students t-test to assess changes in pre-distraction, post-distraction, post-consolidation and 1 year follow-up. Long-term follow-up (2 and 5 years) was interpreted according to mean values. RESULTS The measurements of SNB, ANB, facial convexity angle, overjet and overbite, and soft tissue facial profile showed significant correction of the mandibular retrognathia and malocclusion. The mandibular divergence decreased and mandibular, corpus, and ramus lengths remained stable during the consolidation period. The regression of mandibular measurements towards pre-distraction values was observed in skeletal and dental parameters and soft tissue profiles during the first postoperative year and continued during the 2- to 5-year follow-up period. The achieved mandibular corpus and ramus lengthening was stable while the mandible displayed considerable posterior rotation but no further growth. Orthodontic treatment could not overcome the regression of mandibular measurements to their original values. The maxilla continued its normal growth during the long-term follow-up. Two patients had tracheostomies, but the tube was removed from both during or immediately after distraction. CONCLUSION - Excellent short-term structural results of mandibular DO are not stable during the growth of syndromic children because of restricted mandibular growth. Thus, a re-evaluation of DO timing in the improvement of facial aesthetics must be considered. However, mandibular DO in children with severe airway problems is recommended.

SKELETAL STABILITY OF LE FORT I OSTEOTOMY IN PATIENTS WITH UNILATERAL CLEFT LIP AND PALATE

The skeletal stability of Le Fort I osteotomy was evaluated cephalometrically in 40 consecutive patients with unilateral cleft lip and palate (UCLP) (27 male and 13 female) who were operated on between 1987-1995. Their mean age at the time of operation was 23.7 years (range 16.3-40.4). The onepiece Le Fort I osteotomy was fixed with titanium plates and the osteotomy line was bone-grafted. Neither intermaxillary fixation nor occlusal splints were used postoperatively. Skeletal stability was analysed both horizontally and vertically on cephalograms taken shortly before operation, immediately afterwards, and at six months and at one year postoperatively. The mean maxillary advancement (point A) during the Le Fort I was 3.9 mm (range 0- 8.9) and mean vertical lengthening 4.5 mm (range -0.6-10.5). One year postoperatively the mean maxillary horizontal relapse was 20.5% (0.8 mm, range 0-3.7) whereas the mean vertical relapse was 22.2% (1 mm, range 0-5.7). The vertical relapse reduced from 38% to 8.3% between 1987 and 1995, and there was a positive correlation between the amount of maxillary advancement and relapse both horizontally and vertically.The skeletal stability of Le Fort I osteotomy was evaluated cephalometrically in 40 consecutive patients with unilateral cleft lip and palate (UCLP) (27 male and 13 female) who were operated on between 1987-1995. Their mean age at the time of operation was 23.7 years (range 16.3-40.4). The one-piece Le Fort I osteotomy was fixed with titanium plates and the osteotomy line was bone-grafted. Neither intermaxillary fixation nor occlusal splints were used postoperatively. Skeletal stability was analysed both horizontally and vertically on cephalograms taken shortly before operation, immediately afterwards, and at six months and at one year postoperatively. The mean maxillary advancement (point A) during the Le Fort I was 3.9 mm (range 0-8.9) and mean vertical lengthening 4.5 mm (range -0.6-10.5). One year postoperatively the mean maxillary horizontal relapse was 20.5% (0.8 mm, range 0-3.7) whereas the mean vertical relapse was 22.2% (1 mm, range 0-5.7). The vertical relapse reduced from 38% to 8.3% between 1987 and 1995, and there was a positive correlation between the amount of maxillary advancement and relapse both horizontally and vertically.