Craniofacial microsomia – more than a structural malformation

Abstract Objectives To analyse the prevalence and distribution of craniofacial microsomia (CFM) cases in Finland and their most frequent comorbidities. The second aim was to analyse the patients' need for specialized healthcare services. Materials and methods Data were gathered from two complementary registers: The Register of Congenital Malformations and the Care Register for Social Welfare and Health Care (Hilmo) of the Finnish Institute for Health and Welfare (THL). Results The prevalence of CFM patients in Finland was 1:10 057. They were evenly distributed across the five university hospital districts. Their most frequently used ICD‐10 diagnosis codes were F40‐48 (Neurotic, stress‐related and somatoform disorders), 60% of patients in adolescent and adult psychiatry; Q67.0 (Facial asymmetry), 43% in plastic surgery; Z00.4 (General psychiatric examination, not elsewhere classified), 31% in child psychiatry; Z31.5 (Genetic counselling), 28% in clinical genetics and Q67.40 (Other congenital deformities of the skull, face and jaw, Hemifacial atrophy), 18% in dental, oral and maxillofacial diseases. Of the patients, 70% had had visits in clinical genetics, 60% in plastic surgery, 41% in dental, oral and maxillofacial diseases, 28% in adolescent/adult psychiatry and 21% in child psychiatry. The majority of the patients' plastic surgery visits were concentrated in one university hospital. Other services were mainly provided by patients' own hospital districts. Conclusions Even though the majority of CFM patients' visits in specialized healthcare services are related to correction of facial asymmetry and ear malformations, the obvious need for psychiatric care was apparent in all age groups.

et al reported that 10% of CFM cases had cleft lip/palate and 23% macrostomia. 4 The terminology used for craniofacial microsomia varies and other terms are also used such as hemifacial microsomia (HFM), oculo-auriculo-vertebral dysplasia (OAVS) or Goldenhar syndrome. 2,6 Estimates of the prevalence of CFM range from 1:3500 to 1:45 000. 5 The aetiology of the disorder is unclear, but both genetic and environmental factors, for example, mother's exposure to certain teratogens (such as thalidomide, retinoic acid, primidone and cocaine) during pregnancy have been suggested.
According to one theory, the causal factor might be an early disturbance in the circulatory system. In 1973, Poswillo 7 studied this theory in mice: During the 6th week of gestation, an artificial disruption in stapedial artery blood flow resulted in similar facial disorders as seen in CFM patients. Other, more recently suggested risk factors for CFM include maternal smoking during the second trimester of pregnancy, maternal diabetes and multiple births. [1][2][3] Although most CFM cases are sporadic, it also occurs in families. In these cases, the autosomal inheritance can manifest either dominantly or recessively. The diagnostic challenges in CFM are caused by the wide spectrum of symptoms and the lack of common diagnostic criteria. Pruzansky's well-known classification for CFM (1969) describes the severity of mandibular deformity, while SAT-, OMENS-and OMENS Plus-classifications include also other developmental disorders of the face and soft tissues. With regard to differential diagnostics, CFM includes similar symptoms as, for example, CHARGE, Townes-Brocks and Treacher-Collins syndromes. [1][2][3][8][9][10][11] At the end of 2020, a Working Group of Craniofacial Microsomia published a consensus article focusing on uniform criteria for CFM in Europe. 12 According to a decree of the Ministry of Social Affairs and Health, the diagnostics and treatment of CFM in Finland are carried out in university hospitals. In CFM cases that include cleft lip and/ or palate, the entire treatment protocol is planned and early-stage surgeries are implemented at Helsinki University Hospital, or in cooperation with the Oulu University Hospital. 13,14 For each patient, multidisciplinary treatments and their timing are planned individually, for example, with regard to the schedule of craniofacial growth.
An ear malformation, characteristic of CFM, may range from a small fibroma in front of the ear to microtia or total absence of the auricle. The malformed ear and other soft tissue deficiencies can be repaired with plastic surgery. 6 Ear malformation may also be associated with structural deviations in the auditory ossicles, resulting in hearing loss or deafness. While hearing loss has a huge impact on everyday life, hearing should be monitored repeatedly throughout the growth period. 2,15 Given the increased risk of psychosocial problems during childhood, it is important to provide children with CFM with psychosocial support early on. [15][16][17][18] Nonetheless, differences in experienced quality of life appear in childhood to be small compared to healthy peers. 19 Further, effective monitoring is also needed, because a small, underdeveloped mandible may constrict the respiratory tract and lead to obstructive sleep apnoea (OSA). 2 In the most severe developmental deficiencies, with completely missing condylar cartilage, reconstruction of the mandible may be done with a costochondral graft. Distraction osteogenesis and costochondral grafts early in the growth phase are justified especially when a child with CFM has difficulties breathing or eating. 6 Orthodontic-surgical corrections of severe developmental jaw discrepancies can be made only after growth has ceased. In fact, CFM patients treated during the growth phase may later require a new orthodontic-surgical treatment period once they have reached full growth. 6 For a more detailed description of early treatment of clefts, ear problems and OSA, see, for example, the review by Hopkins et al 20 In order to effectively arrange public healthcare services that meet the needs of a special group of patients, it is vital to be familiar with the prevalence and distribution of these cases as well as the associated resource needs. This study aimed at analysing (1) the prevalence and distribution of CFM cases in Finland, (2) the prevalence of other, most common comorbidities and (3) the use of specialized healthcare services related to these diagnoses. Students whose studies have lasted for more than 1 year, have, since 1994, had the option to change their domicile to the municipality where they study. 22 The distribution of ICD-10 diagnosis codes was examined in the following nine specialties: adolescent psychiatry, adult psychiatry, plastic surgery, child psychiatry, clinical genetics, dental, oral and maxillofacial diseases, clinical dental care, orthodontics and oral and maxillofacial surgery. For each patient, each ICD-10 diagnosis code was considered only once (either as a primary or secondary diagnosis) in each specialty. The number of visits without any ICD-10 diagnosis code was considered in assessment of the treatment burden in each specialty.

| MATERIAL S AND ME THODS
The prevalence of CFM cases and CFM patients' visits in different clinics were examined nationwide by numbers and percentages.
Gender differences and distributions of the visits between hospital districts were analysed with the Kruskal-Wallis test (IBM SPSS Statistics, Version 25). P-values of <0.05 were interpreted as statistically significant.

| RE SULTS
Between genders or hospital districts, no statistically significant differences were found in the occurrence of CFM or in the num- Visits related to clinical genetics and psychiatry occurred mainly in patients' own hospital districts; the same was true of visits related to dental, oral and maxillofacial diseases. For two patients, some of the visits in the latter specialty were handled in another hospital district. The majority of plastic surgery visits were concentrated in one university hospital. Two of the four university hospitals referred there all, and two others, 50%-67% of the cases, while one in three cases was treated in cooperation.    19 However, although children and adolescents with CFM feel that they are doing better than their parents expect, they also face bullying. 15,25 Therefore, it is more than vital to recognize the need for psychological support from early on.

| DISCUSS ION
Visits to the clinical genetics specialty provide families with a CFM-affected child with support and information about the developmental disorder. Somewhat surprisingly, only slightly more than one in two children and adolescents with CFM under 18 years of age had had such visits. It is possible that the visits had not been offered routinely; it is also possible that families had not prioritized these visits in relation to various other treatment procedures. Given that the adults included in the current study were young, only 18-25 years old, the low participation in genetic counselling may be understandable. However, in a recent article, Birgfeld and Heike 2 recommend that a genetic counselling is provided for each CFM patient in both childhood and adulthood.
With regard to the structures affected by the developmental disorder, the need for plastic surgery among CFM patients is obvious.
In the current study, almost two in three patients needed plastic sur-  26 Prior to that, application of ICD-10 diagnosis codes had not been a common practice and all markings had been written manually on patient records. Presumably due to the tight implementation time, a share of ICD-10 diagnosis codes were missing from the registers. However, all visits -with or without an ICD-10 diagnosis code -were included in assessments of treatment load in each specialty.
As stated, there was variation also in recording practices with regards to time periods and treatment units.
• Treatment of CFM is multidisciplinary. Although most of the patients' visits to specialized medical care are related to functional and aesthetic corrections, the psychological burden of CFM affects patients in all age groups.
• Due to the lack of ICD-10 diagnosis codes and variation in recording practices, it is obvious that the actual need for various treatments exceeds the numbers presented in this study.

ACK N OWLED G EM ENT
Open access funding enabled and organized by ProjektDEAL.

CO N FLI C T O F I NTE R E S T
The authors report no conflict of interest.

DATA AVA I L A B I L I T Y S TAT E M E N T
Research data are not shared.