[Oral manifestations of KID syndrome: rare clinical case]. / Stomatologicheskie proiavleniia KID-sindroma: redkii klinicheskii sluchai.

The paper presents a rare clinical case of an infant with KID (Keratitis, Ichthyosis, Deafness) syndrome (about 100 patients reported so far) admitted for histological verification of oral mucosa lesions. Disease pathogenesis defines inadequate reparation and skin and mucosa innate immunity defect leading to higher incidence of bacterial and fungal infections, so the 4-years old girl received treatment for vegetating candidiasis of the oral mucosa for several weeks with no clinical improvement. Initial examination showed that the oral lesions resulted from sharp edges of severely affected carious teeth. Histological study of multifocal biopsy revealed pyogenic granulomas and no signs of SCC. Teeth extraction and symptomatic treatment leaded to significant clinical improvement and some remained mucosal changes may be attributed to syndrome manifestations.

Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent de novo mutation in the POLD1 gene.

Segmental progeroid syndromes with lipodystrophy are extremely rare, heterogeneous, and complex multi-system disorders that are characterized by phenotypic features of premature aging affecting various tissues and organs. In this study, we present a "sporadic/isolated" Japanese woman who was ultimately diagnosed with mandibular hypoplasia, deafness, progeroid features, and progressive lipodystrophy (MDPL) syndrome (MIM #615381) using whole exome sequencing analysis. She had been suspected as having atypical Werner syndrome and/or progeroid syndrome based on observations spanning a 30-year period; however, repeated genetic testing by Sanger sequencing did not identify any causative mutation related to various subtypes of congenital partial lipodystrophy (CPLD) and/or mandibular dysplasia with lipodystrophy (MAD). Recently, MDPL syndrome has been described as a new entity showing progressive lipodystrophy. Furthermore, polymerase delta 1 (POLD1) gene mutations on chromosome 19 have been identified in patients with MDPL syndrome. To date, 21 cases with POLD1-related MDPL syndrome have been reported worldwide, albeit almost entirely of European origin. Here, we identified a de novo mutation in exon 15 (p.Ser605del) of the POLD1 gene in a Japanese case by whole exome sequencing. To the best of our knowledge, this is the first identified case of MDPL syndrome in Japan. Our results provide further evidence that mutations in POLD1 are responsible for MDPL syndrome and serve as a common genetic determinant across different ethnicities.

Dentinogenesis imperfecta 1 with or without progressive hearing loss is associated with distinct mutations in DSPP.

Dentinogenesis imperfecta 1 (DGI1, MIM 125490) is an autosomal dominant dental disease characterized by abnormal dentin production and mineralization. The DGI1 locus was recently refined to a 2-Mb interval on 4q21 (ref. 1). Here we study three Chinese families carrying DGI1. We find that the affected individuals of two families also presented with progressive sensorineural high-frequency hearing loss (gene DFNA39). We identified three disease-specific mutations within the dentin sialophosphoprotein gene (DSPP) in these three families. We detected a G-->A transition at the donor-splicing site of intron 3 in one family without DFNA39, a mutation predicted to result in the skipping of exon 3. In two other families affected with both DGI1 and DFNA39, however, we identified two independent nucleotide transversions in exons 2 and 3 of DSPP, respectively, that cause missense mutations of two adjacent amino-acid residues in the predicted transmembrane region of the protein. Moreover, transcripts of DSPP previously reported to be expressed specifically in teeth are also detected in the inner ear of mice. We have thus demonstrated for the first time that distinct mutations in DSPP are responsible for the clinical manifestations of DGI1 with or without DFNA39.

Eye pain and blurred vision as main complaints in a new case with MDPL syndrome.

INTRODUCTION: We report a novel phenotype of mandibular hypoplasia, deafness, and progeroid features with lipodystrophy (MDPL) syndrome with POLD1 mutation in a Chinese girl. CASE DESCRIPTION: Diabetic retinopathy was detected as the primary manifestation in a Chinese girl with MDPL syndrome carrying a known POLD1 mutation (c.1812_1814delCTC, p.Ser605del). Typical characteristics of the syndrome including mandibular hypoplasia, deafness, progeroid features, and diabetes were detected after comprehensive examinations. The patient suffered from blurred vision and eye pain due to the neovascularization of the retina (vitreous hemorrhage and retinal detachment) and iris (neovascular glaucoma). The literature review revealed that the prevalence of hepatomegaly and abnormal triglyceride levels were significantly higher in female than in male with MDPL syndrome carrying POLD1 mutations. CONCLUSION: These results expand our knowledge regarding the clinical phenotypes of MDPL syndrome with POLD1 mutations. Diabetic retinopathy is a non-negligible complication of MDPL syndrome. The phenotype varies among female and male patients with the syndrome. Hepatomegaly and abnormal triglyceride levels are more common in female patients with MDPL syndrome.

NDRG1-linked Charcot-Marie-Tooth disease (CMT4D) with central nervous system involvement.

Charcot-Marie-Tooth disease type 4D (CMT4D) is an autosomal recessive demyelinating polyneuropathy, associated with deafness exclusively found in Gypsies and resulting from a homozygous R148X mutation in the N-myc downstream-regulated gene 1 (NDRG1). We report the detailed phenotypic study of a family without Gypsy ancestry, who presented with severe demyelinating polyneuropathy, deafness, subcortical white matter abnormalities on brain magnetic resonance imaging studies, and the R148X mutation in NDRG1. For the first time, central nervous system white matter lesions are demonstrated in CMT4D. This report extends the clinical knowledge of CMT4D and indicates that the role of the R148X mutation in NDRG1 in the central nervous system should be further studied.

Generalised EPG treatment effect in a cochlear implant user maintained after 2 years.

PURPOSE: The aim of this study was to evaluate speech therapy using electropalatography (EPG) in home training of persistent articulation errors in a cochlear implant user with hearing impairment. There was a particular focus on aspects of maintenance of training effects and possible transfer to connected speech. METHOD: The participant was a young woman, deaf from early childhood and a cochlear implant user from pre-school age. Treatment effects were evaluated using a single-subject design with multiple measures. RESULT: Instrumental and perceptual outcome measures showed a clear improvement in the production of the treatment target /É¡/ in single words and sentences after 4 months of therapy (17 hours). The results were maintained at 3, 6 and 24 months after intervention. Also, /É¡/ in connected speech, consisting of text reading and spontaneous speech, showed a significant difference between before and after treatment and at long-term follow-up. CONCLUSION: The results show that EPG used in home training can be an efficient method for treating persistent speech disorders associated with hearing impairment and that the treatment effect appears to maintain.

Waardenburg syndrome type 2: an orthodontic perspective.

Waardenburg syndrome is a rare form of neurocristopathy. It is a disorder in the development of neural crest cells, caused by an altered cellular migration during the embryonic phase. That alteration causes an association of different abnormalities such as pigmentary disturbances of the hair, iris, skin, stria vascularis of the cochlea, dystopia canthorum and sensorineural hearing loss. We report a case of a 14-year-old Romanian male, with a family history of Waardenburg syndrome (mother) and Usher syndrome (father - congenitally sensorineural hearing loss and retinal degeneration). The case particularities are: the correlation between malocclusion and Waardenburg syndrome due to hypoplastic alae nasi and also factors that produced hearing loss, which could be Waardenburg syndrome, Usher syndrome or the presence of the connexin 26 (W24X) gene mutation.

A new look at osteogenesis imperfecta. A clinical, radiological and biochemical study of forty-two patients.

In a clinical, radiological and biochemical study of forty-two patients from Oxford with osteogenesis imperfecta, it was found that patients could be divided simply into mild, moderate and severe groups according to deformity of long bones. In the severe group (seventeen patients) a family history of affected members was uncommon and fractures began earlier and were more frequent than in the mild group (twenty-two patients); sixteen patients in the severe group had scoliosis and eleven had white sclerae; no patients in the mild group had white sclerae or scoliosis. Radiological examination of the femur showed only minor modelling defects in patients in the mild group, whereas in the severe group five distinct appearances of bone (thin, thick, cystic and buttressed bones, and those with hyperplastic callus) were seen. The polymeric (structural) collagen from skin was unstable to depolymerisation in patients in the severe group, but normal in amount, whereas the reverse was found in the mild group. This division according to long bone deformity may provide, a basis for future research more useful than previous classifications.

Deafness, ichthyosiform erythroderma, corneal involvement, photophobia and dental dysplasia.

Early childhood deafness, congenital non-bullous ichthyosiform erythroderma, corneal involvement, photophobia, chronic blepharoconjunctivitis, hypotrichosis, anhidrosis, hyperkeratosis of the nails and dental dysplasia were the symptoms observed in the 19-year-old girl described in this paper. The literature comprises reports on 8 patients with this syndrome, which McKusick (1975) listed as no. 24215.

Premature cataracts associated with generalized lentigo.

Generalized lentigo (leopard syndrome) is an autosomal dominant trait characterized by lentigo, sensorineural deafness, retarded growth (below 25%), ocular hypertelorism, mandibular prognathism, pectus carinatum or excavatum, dorsal kyphosis, winging of the scapulae, valvular pulmonary artery stenosis, electrocardiographic conduction defects, and genitourinary defects. Ocular evaluations of patients with generalized lentigo have revealed the appearance of multiple small white punctate and comma-shaped opacities in the cortex and nuclci of the lenses of affected patients. On the basis of age of the patients examined, it would seem that the corneal opacities first appear in the third decade. Although the opacities may be extensive, the lens opacities do not appear to impair visual function until approximately twenty years after they first appear.

[A case of hereditary motor and sensory neuropathy with vocal cords palsy and diaphragmatic weakness].

A case of hereditary motor and sensory neuropathy (HMSN) type 1 (Charcot-Marie-Tooth disease (CMT)) is reported with vocal cords palsy, deafness, diaphragmatic weakness, and cerebellopontine atrophy. A 42-year-old man was admitted to our hospital in April, 1991 with marked respiratory distress. He had been diagnosed as having CMT 14 years previously. On admission to our hospital, he revealed dyspnea with marked stridor during inspiration. Physical examination showed marked use of respiratory accessory muscles with thoracoabdominal paradox in the supine position. Neurologic examination revealed tonic pupils, mild bilateral weakness of facial muscles, deafness, mild bulbar palsy, severe wasting and weakness in both proximal and distal muscles of the arms and legs, areflexia, distal loss of all sensory modalities. Pes cavus and hammer toe were present. Movement of upper extremities was ataxic. No hypertrophic changes were noted in his peripheral nerves. Peripheral nerve conduction study showed undetectable both sensory and motor action potentials. Electromyography showed evidence of denervation, more marked in distal muscles. Auditory brain stem response was undetectable. Chest radiographic film showed a normal-sized heart with marked elevation of both hemidiaphragm. Laryngofiberscopy confirmed the presence of bilateral vocal cord paralysis without tumor formation, inflammation or anomaly. The vocal cords lay near the midline and did not show any movement during respiration. Moderate cerebellopontine atrophy was confirmed on MRI scan. A sural nerve section showed severe decrease of myelinated fibers, and onion bulbs. Diagnosis of HMSN type 1 was made by clinical, electrodiagnostic, and sural nerve sections study.(ABSTRACT TRUNCATED AT 250 WORDS)

[KID syndrome: a cause of pachydermatoglyphia]. / KID syndrome: une cause de pachydermatoglyphie.

INTRODUCTION: The KID syndrome is a rare ectodermal dysplasia associating erythrokeratodermia, deafness and keratitis. Other disorders such as sensitivity to infections or hypohidrosis may be associated. Pachydermatoglyphia is characterized by diffuse hyperkeratosis in which the dermatoglyphe crests are accentuated in thickness and height. CASE REPORT: We report the case of a KID syndrome in a young girl, born of non-consanguine parents and without any familial context. The classical elements of this dysplasia were present: erythrokeratoderma with dryness and roughness of the whole tegument, plicatured pachydermia of the knees, facial erythema, grooves around the mouth, hypotrichosis of the lashes and eyebrows, deafness, and ophthalmologic involvement. Involvement of the palms was characterized by the pachydermatoglyphic aspect. DISCUSSION: In this case report, the palmar keratoderma corresponded to the original description of pachydermatoglyphia and we consider that the KID syndrome should be integrated as a possible etiology of pachydermatoglyphia.

[Familial expansive osteolysis otological and dental manifestations of genetic origin]. / L'ostéolyse expansive familiale. Manifestations otologiques et dentaires d'origine génétique.

OBJECTIVES: Familial Expansive Osteolysis (FEO) ist a rare autosomal dominant bone dysplasia. The disease can show general and focal skeletal alterations, the latter having a predominantly peripheral distribution. Onset occurs after the second decade of life. PATIENTS AND METHODS: We present the study, of 30 years, of a family consisting of 49 members covering five generations. RESULTS: Among the 35 members studied, 18 have familial expansive osteolysis (FEO). The first clinical sign of the condition is transmission deafness at an early age. The features of the teeth has a unique and characteristic appearance. Thinning of the cortical bone leads to severe, painful, disabling deformities. Serum alkaline phosphatase, and urinary hydroxyproline and deoxipyridinoline are elevated. Calcium and parathyroid hormone are normal. Treatment with diphosphonates, calcitonin and vitamin D has been unsuccessful. We present the surgical technology and the results to short and long term of 13 interventions on 8 patients. CONCLUSION: Progressive osteoclastic reabsorption accompanied by weak osteoblastic activity results in medullary expansion characterized by rarefaction of the bone marrow, which is replaced by fibrous tissue and fat. FEO is histologically similar to Paget disease, but the age of onset, the distribution of the bone lesions, the dental and middle ear alterations, and the clinical progression are different. These features also differentiate FEO from fibrous dysplasia, fibrocystic osteitis and imperfect osteogenesis. The gene responsible for FEO is located in the 18q21-22 chromosome region. Mutations in TNFRSF11A, the gene encoding receptor activator of nuclear factor-kappa-B (RANK), has been recently identified as the cause of FEO. A duplication of 18 base pairs in exon 1 of the TNFRSF11A gene suggests that this corresponds to the site of the anomaly and can be considered a "hot spot" for mutations.

Prevalence of dental caries in handicapped children of Calcutta.

A total of 1042, 3-14-year-old children with different types of handicapping conditions when recorded for dental caries using WHO 1987 caries recording index revealed that dental caries experience was higher in handicapped children than normal children. The prevalence of dental caries was highest in mentally retarded children followed by cerebral palsied, blind, epileptic, physically handicapped, children with Down's syndrome and deaf and dumb. Higher deft+DMFT was recorded in mandibular teeth compared to maxillary teeth.

Caries experience and oral hygiene status of blind, deaf and mentally retarded female children in Riyadh, Saudi Arabia.

OBJECTIVE: To determine the caries experience and oral hygiene status in blind, deaf and mentally retarded female children in Riyadh, Saudi Arabia. METHOD: All (N=218) the 6-7-year-old and 11-12-year-old blind, deaf and mentally retarded female children registered with the Presidency of Girls' Education schools in Riyadh were examined for dental caries and oral hygiene in a dental operatory setting. RESULTS: All (100%) the blind 6-7-year-old had caries with a mean dmft score of 6.58 (SD 2.02). The caries prevalence in blind 11-12-year-olds was 88.2% with a mean DMFT score of 3.89 (SD 2.67). Among 6-7-year-old blind children 8.3 %, and in 11-12-year-old blind children 29.4% had good oral hygiene. The caries prevalence in deaf 6-7-year-olds was 95.7% with a mean dmft score of 7.35 (SD 3.51). The caries prevalence in 11-12-year-old deaf children was 93% with a mean DMFT of 5.12 (SD 3.45). Less than one-fifth (17.4%) of the 6-7-year-old deaf children and only 7.0% of 11-12-year-old deaf children had good oral hygiene. The caries prevalence in mentally retarded 6-7-year-old was 93.9% with a mean dmft of 8.00 (SD 4.1). All the mentally retarded 11-12-year-old had carious teeth with a mean DMFT score of 5.81 (SD 2.95). Only 3.1% of the mentally retarded 6-7-year-old and none of the mentally retarded 11-12-year-olds had good oral hygiene. CONCLUSIONS: Caries prevalence and severity in all the three groups of female special children were very high, and the number of children with good oral hygiene was very low.

Clinical aspects of congenital syphilis with Hutchinson's triad.

Congenital syphilis is an infectious disease caused by Treponema pallidum transmitted by infected mother to her baby during pregnancy. Late congenital syphilis is recognised with 2 or more years after birth. One of the main aspects is observed with the triad of Hutchinson, characterised by the presence of interstitial keratitis, eighth nerve deafness and Hutchinson's teeth. This manuscript reports a case of late congenital syphilis presenting with Hutchinson's triad at an age of 7 years. These clinical features are related to syphilis present during pregnancy and at birth, however they commonly become apparent after 5-years of age.

A novel syndrome of mandibular hypoplasia, deafness, and progeroid features associated with lipodystrophy, undescended testes, and male hypogonadism.

CONTEXT: Mandibuloacral dysplasia (MAD) is an autosomal recessive progeroid disorder associated with type A (partial) or B (generalized) lipodystrophy and is due to mutations in lamin A/C (LMNA) or zinc metalloproteinase (ZMPSTE24) genes. OBJECTIVE: The objective of the study was to report a novel syndrome with some overlapping features with MAD. RESULTS: We report seven patients with mandibular hypoplasia, deafness, progeroid features (MDP), and associated lipodystrophy. These patients have similar features to MAD patients such as hypoplastic mandible, beaked nose, stiff joints, and sclerodermatous skin. However, the patients did not harbor any disease causing variants in LMNA or ZMPSTE24 and showed distinct characteristics such as sensorineural hearing loss and absence of clavicular hypoplasia and acroosteolysis. All males with MDP had undescended testes and were hypogonadal. One adult female showed lack of breast development. Skinfold thickness, dual-energy X-ray absorptiometry and whole-body magnetic resonance imaging for body fat distribution revealed a lack of lipodystrophy in a prepubertal female but a progressive loss of sc fat presenting with partial lipodystrophy in young adults and generalized lipodystrophy in older patients. CONCLUSIONS: Patients with MDP syndrome have a few overlapping but some distinct clinical features as compared with MAD, suggesting that it is a novel syndrome. The molecular basis of MDP syndrome remains to be elucidated.