Malocclusions and craniofacial anomalies in a child with velo-cardio-facial syndrome.

Velo-Cardio-Facial syndrome (VCFS), also called 22q11.2 microdeletion syndrome, is a rare pathology. The syndrome is caused by 22q11.2 deletion, recognized as one of the most frequent pathogenic human microdeletions. The scope and severity of the phenotypic expression of 22q11.2 microdeletion is characterised by high variability, although cleft palate and congenital conotruncal malformations are among the clinical features often associated with that syndrome. In the presented case of a boy patient with submucous cleft palate and congenital cardiac defect, 22q11.2 microdeletion was identified at the age of 13 months. In the presented paper particular emphasis was placed on the issue of dental and orthodontic care in patients with changes in the oral cavity and the craniofacial area, as well as on the possibilities of treatment and prophylaxis. The necessity to perform a thorough examination of the oral cavity in infants was also underlined as a vital element of clinical assessment, in particular in the case of co-occurring structural defects of internal organs.

Characterization of a 8q21.11 microdeletion syndrome associated with intellectual disability and a recognizable phenotype.

We report eight unrelated individuals with intellectual disability and overlapping submicroscopic deletions of 8q21.11 (0.66-13.55 Mb in size). The deletion was familial in one and simplex in seven individuals. The phenotype was remarkably similar and consisted of a round face with full cheeks, a high forehead, ptosis, cornea opacities, an underdeveloped alae, a short philtrum, a cupid's bow of the upper lip, down-turned corners of the mouth, micrognathia, low-set and prominent ears, and mild finger and toe anomalies (camptodactyly, syndactyly, and broadening of the first rays). Intellectual disability, hypotonia, decreased balance, sensorineural hearing loss, and unusual behavior were frequently observed. A high-resolution oligonucleotide array showed different proximal and distal breakpoints in all of the individuals. Sequencing studies in three of the individuals revealed that proximal and distal breakpoints were located in unique sequences with no apparent homology. The smallest region of overlap was a 539.7 kb interval encompassing three genes: a Zinc Finger Homeobox 4 (ZFHX4), one microRNA of unknown function, and one nonfunctional pseudogen. ZFHX4 encodes a transcription factor expressed in the adult human brain, skeletal muscle, and liver. It has been suggested as a candidate gene for congenital bilateral isolated ptosis. Our results suggest that the 8q21.11 submicroscopic deletion represents a clinically recognizable entity and that a haploinsufficient gene or genes within the minimal deletion region could underlie this syndrome.

Wide Fontanels, Delayed Speech Development and Hoarse Voice as Useful Signs in the Diagnosis of KBG Syndrome: A Clinical Description of 23 Cases with Pathogenic Variants Involving the ANKRD11 Gene or Submicroscopic Chromosomal Rearrangements of 16q24.3.

KBG syndrome is a neurodevelopmental autosomal dominant disorder characterized by short stature, macrodontia, developmental delay, behavioral problems, speech delay and delayed closing of fontanels. Most patients with KBG syndrome are found to have a mutation in the ANKRD11 gene or a chromosomal rearrangement involving this gene. We hereby present clinical evaluations of 23 patients aged 4 months to 26 years manifesting clinical features of KBG syndrome. Mutation analysis in the patients was performed using panel or exome sequencing and array CGH. Besides possessing dysmorphic features typical of the KBG syndrome, nearly all patients had psychomotor hyperactivity (86%), 81% had delayed speech, 61% had poor weight gain, 56% had delayed closure of fontanel and 56% had a hoarse voice. Macrodontia and a height range of -1 SDs to -2 SDs were noted in about half of the patients; only two patients presented with short stature below -3 SDs. The fact that wide, delayed closing fontanels were observed in more than half of our patients with KBG syndrome confirms the role of the ANKRD11 gene in skull formation and suture fusion. This clinical feature could be key to the diagnosis of KBG syndrome, especially in young children. Hoarse voice is a previously undescribed phenotype of KBG syndrome and could further reinforce clinical diagnosis.

[Moebius syndrome with facial-dental impairments - rare or rather seldom diagnosed syndrome?]. / Zespól Moebiusa Z Zaburzeniamitwarzowo"zebowymi. Zespól Rzadkowystepujacy, Czy Rzadko Rozpoznawany?

As publications on craniofacial anomalies, malocclusions and dental complications recognised in patients suffering from Moebius syndrome are scarce, the authors of this paper decided to discuss the above aspects in broader terms along with the possibilities offered by orthodontic treatment. The etiology of Moebius syndrome has not hitherto been discovered, however the opinion prevails that it is brought on by multiple factors and conditions. In the analysed case, Moebius syndrome was diagnosed only when the patient was 6 years old. Based on the clinical examination, typical characteristics of the syndrome were observed: craniofacial dysmorphism as well as foot development disorder in the form of talipes equinovarus (club foot). Moreover, Type II Angle's classification of malocclusion was detected - crowded teeth in the mandible and maxilla and hypoplastic enamel. Cephalometric analysis identified retruded position of the mandible against the cranial base, protruded position of the maxilla, shortening of posterior face height, protrusion of incisors in the maxilla. The orthopantomogram showed the presence of all permanent teeth. At the beginning of the orthodontic treatment removable appliances were used, but despite good cooperation on the part of the patient, only a slight improvement was observed. Further orthodontic treatment envisaged extraction of permanent teeth and use of fixed appliances while waiting for the improvement of occlusion.

Hypomyelination, hypogonadotropic hypogonadism, hypodontia - First Polish patient.

The term 4H was suggested for the rare, novel entity with hypomyelination, hypogonadotropic hypogonadism and hypodontia. A combination of clinical findings with ataxia and endocrinological abnormalities, brain MRI and dentition history are crucial for the diagnosis. We present the first Polish patient with this disease with repeated brain MRI, MRI of the pituitary gland and orthopantomogram.

[Variable clinical expression of familial Incontinentia Pigmenti syndrome - presentation of three cases]. / Zróznicowanie ekspresji fenotypowej rodzinne wystepujacego zespolu Incontinentia Pigmenti - prezentacja trzech przypadków.

Incontinentia Pigmenti (IP, Bloch-Sulzberger syndrome, OMIM 308300) is a rare X-linked dominant genodermatosis, usually lethal in males in the prenatal period. Wide spectrum of clinical expression consists of skin hyperpigmented lines and swirling patterns, dysplastic teeth and nails, and in 30% central nervous system abnormalities including seizures, microcephaly and intellectual disability (10% of cases). In 80% of IP cases, the disease is caused by a large-scale deletion of exons 4 to 10 of the NEMO gene. Three cases of variable expression of Incontinentia Pigmenti are presented. In a one-year-old girl, her mother and grandmother molecular analysis revealed the same typical deletion of the NEMO gene. In the proband, characteristic skin lesions were detected located over the trunk and lower limbs. Characteristic evolution of the changes was observed. In the mother, expression of the disease was much milder, whereas in the grandmother lesions were restricted to the fingernails. Clinical characteristics and pedigree data are described.