INTU-related oral-facial-digital syndrome XVII: Clinical spectrum of a rare disorder.

Oral-facial-digital syndromes (OFDSs) as a subgroup of ciliopathies are rare genetic disorders characterized by the association of abnormalities of the face, oral cavity, and extremities. OFDS XVII is a recently described subtype of OFDS that presents with developmental delay, facial dysmorphism, high palate, tongue nodules, brain malformations, cardiac anomaly, polydactyly, renal malformation, and various other findings. OFDS XVII is caused by biallelic variants in INTU gene and is inherited autosomal recessively. Intu is part of the CPLANE protein module that has an essential role in the ciliary transport system and function. INTU pathogenic variants have been reported in two patients with OFDS XVII, in two patients with short-rib thoracic dysplasia-20 with polydactyly (SRTD20), and one with nephronophthisis so far. We report the third family in the literature with OFDS XVII, with urogenital malformations as an additional finding.

Papillon-Léage and psaume syndrome patient with multiple dental and orofacial anomalies.

Papillon-Léage-Psaume Syndrome, also known as oral-facial-digital syndrome (OFDS) type I, describes a group of neurodevelopmental disorders that are characterized by anomalies of the oral cavity, facial features, and the digits. Central nervous system (CNS) anomalies and visceral organ abnormalities such as kidney, pancreas, and ovarian cysts can also be seen in these patients. Among 13 potential types, female-inherited OFDS type I is the most common and it has been reported to be lethal in males. After the identification of the genetic relation of OFDS in 2001, it is now known that, except X-linked OFDS Type I and VIII, generally all types of OFDSs are autosomal recessive. The dentist's knowledge about the syndrome can reduce the development of physical and dental anomalies by facilitating early diagnosis. This article presents a patient with Papillon-Léage-Psaume Syndrome (Oral-Facial-Digital Syndrome Type I).

Successful treatment of facial milia in an infant with orofaciodigital syndrome type 1.

We report the successful treatment of multiple facial milia with manual extraction and tretinoin in a child with orofaciodigital syndrome type 1. Treatment with topical medications may be insufficient in individuals with orofaciodigital syndrome type 1, and pitted scarring is often a sequala. This case demonstrates that manual extraction is well tolerated and effective in the treatment of multiple milia. In addition, clinicians need to be aware of this rare genetic condition, which commonly presents de novo and can lead to significant morbidity if untreated.

ORAL-FACIAL-DIGITAL SYNDROME TYPE I (CLINICAL CASE).

The oral-facial-digital syndrome belongs to a group of hereditary diseases, manifested by multiple birth defects (usually, the face and fingers). At the current stage, there are 14 genetic variations of the oral-facial-digital syndrome. The presence of various abnormalities of the oral cavity, face and fingers is common for all of them, but each syndrome has a specific phenotype or type of inheritance. The etiology of this syndrome is unknown. It is inherited in an X-linked dominant pattern. Aim of the study: to describe and analyze the clinical case of oral-facial-digital syndrome. Data of the patient (Kira M., 11 months old): clinical-anamnestic examination, chest radiography, ultrasound investigation, molecular-genetic testing OFD1. Results Numerous miliae are detected on the face and ears of the child. Facial dysmorphy (large wide eyes, epicantus, wide nose bridge, telecantus, small mouth, small beak shaped nose, hypoplasia of the wings of the nose, small chin). The large fontanel is closed. Focal alopecia and dry hair are noted. Syndactyly of 2nd-3rd toes, asymmetrical shortening of the index finger of the right hand. Oral cavity examination reveals cleft palate, ankyloglossy and tongue lobulation. Transcranial ultrasonography: M echodex = 50.0 mm. M echosin = 52.0 mm. VIII = 6.9 mm (N up to 3.0 mm). V latdex = 24.4 mm, V latsin = 25.0 mm (N up to 16.0 mm). Neurologist's consultation: "Congenital brain malformation: agenesis of corpus callosum, congenital cerebral cysts." Ultrasound examination of the abdominal organs detected liver enlargement (anteroposterior size of the right lobe: 78 mm (N up to 65 mm), left lobe: 0.38 mm (+1.5 cm) Conclusion Oral-facial-digital syndrome type I is an inherited pathology, which in most cases is diagnosed immediately after birth on the basis of oral, facial and digital anomalies. Molecular genetic study makes it possible to confirm this disease and provide counseling to family members. Elimination of some developmental defects (hard palate plastic, correction of frenulum hyperthrophy), as well as a properly selected complex of therapeutic and rehabilitation measures greatly improves the quality of life of the patient and contributes to a favorable forecast.

Oral-facial-digital syndrome type 1 in males: Congenital heart defects are included in its phenotypic spectrum.

Oral-facial-digital syndrome type 1 (OFD1; OMIM# 311200) is an X-linked dominant ciliopathy caused by mutations in the OFD1 gene. This condition is characterized by facial anomalies and abnormalities of oral tissues, digits, brain, and kidneys. Almost all affected patients are female, as OFD1 is presumed to be lethal in males, mostly in the first or second trimester of pregnancy. Live born males with OFD1 are a rare occurrence, with only five reported patients to date. In four patients the presence of a congenital heart defect (CHD) was observed. Here, we report an affected male fetus with a hemizygous de novo mutation in OFD1 (c.2101C>T; p.(Gln701*)). Ultrasound examination demonstrated severe hydrocephalus, a hypoplastic cerebellum and a hypoplastic left ventricle of the heart. The pregnancy was terminated at 16 weeks of gestation because of poor prognosis. Post-mortem examination of the fetus confirmed severe hypoplasia of the left ventricle of the heart. We emphasize that CHDs should be included in the phenotypic spectrum of OFD1 in males. This justifies molecular analysis of OFD1 when CHD is encountered prenatally in combination with one or more phenotypic features previously described in the OFD1 gene alteration spectrum. The underlying pathogenesis of CHD in OFD1 (and other ciliopathies) probably involves dysfunction of the primary cilia regarding coordination of left-right signalling during early heart development. Whether these CHDs wholly or partly result from defective left right signalling, in which different types of cilia are known to play a critical role, remains a topic of research.

Association of oral-facial-digital syndrome type VI (Varadi-Papp syndrome) with optochiasmatic pilocytic astrocytoma.

INTRODUCTION: Varadi-Papp syndrome (VPS) or oral-facial-digital syndrome type VI (OFDS-VI) is a rare autosomal recessive disorder distinguished from other OFDSs by metacarpal abnormalities with central polydactyly and by cerebellar abnormalities. It can be associated with central nervous system tumors, which most commonly has been a hypothalamic hamartoma. CLINICAL CASE REPORT: The boy had unusual facial features, developmental delay, limb malformations, and other phenotypic anomalies suggestive of VPS. X-ray of the hand and feet showed right hand polydactyly. He also had a deep wider peduncular fossa, thickened superior cerebellar peduncle, and inferior vermian hypoplasia along with optochiasmatic tumor. The patient underwent a right pterional craniotomy and tumor decompression. Histopathology was suggestive of a pilocytic astrocytoma. CONCLUSION: This is the first case in available literature in which the OFDS-VI has been associated with an optochiasmatic pilocytic astrocytoma. We suggest an expansion of the disease spectrum of OFDS-VI to include the association of optochiasmatic pilocytic astrocytoma.

Orofacial digital syndrome type 1: an underlying cause of chronic renal failure.

Orofacial digital syndrome type 1 is condition which is characterized with, in addition to oral-facial and digital congenital anomalies, polycystic renal disease in most patient, and the prognosis is dependent on renal involvement in such patients. Our case was a 22-year-old patient who was presented with clinical picture of chronic renal failure, was started on hemodialysis and had took our attention due to oral, facial and digital anomalies in addition to polycystic renal disease.

Developmental disorders of the dentition: an update.

Dental anomalies are common congenital malformations that can occur either as isolated findings or as part of a syndrome. This review focuses on genetic causes of abnormal tooth development and the implications of these abnormalities for clinical care. As an introduction, we describe general insights into the genetics of tooth development obtained from mouse and zebrafish models. This is followed by a discussion of isolated as well as syndromic tooth agenesis, including Van der Woude syndrome (VWS), ectodermal dysplasias (EDs), oral-facial-digital (OFD) syndrome type I, Rieger syndrome, holoprosencephaly, and tooth anomalies associated with cleft lip and palate. Next, we review delayed formation and eruption of teeth, as well as abnormalities in tooth size, shape, and form. Finally, isolated and syndromic causes of supernumerary teeth are considered, including cleidocranial dysplasia and Gardner syndrome.

Orthodontic treatment of a patient with oral-facial-digital syndrome.

Oral-facial-digital syndrome is characterized by heterogeneous clinical features involving malformations of the face, oral cavity, and digits. The syndrome has been reported only in women, suggesting that it is lethal in males. Affected females have malformations of the oral cavity (cleft palate, lip and tongue, abnormal dentition, and hamartomas), face (hypertelorism and milia), and digits (syndactyly, brachydactyly, and polydactyly). In this article, we report the orthodontic treatment of a 21-year-old woman with oral-facial-digital syndrome.

Renal insufficiency, a frequent complication with age in oral-facial-digital syndrome type I.

The oral-facial-digital syndrome type I (OFD I) is characterized by multiple congenital malformations of the face, oral cavity and digits. A polycystic kidney disease (PKD) is found in about one-third of patients but long-term outcome and complications are not well described in the international literature. Renal findings have been retrospectively collected in a cohort of 34 females all carrying a pathogenic mutation in the OFD1 gene with ages ranging from 1 to 65 years. Twelve patients presented with PKD - 11/16 (69%) if only adults were considered -with a median age at diagnosis of 29 years [IQR (interquartile range) = (23.5-38)]. Among them, 10 also presented with renal impairment and 6 were grafted (median age = 38 years [IQR = (25-48)]. One grafted patient under immunosuppressive treatment died from a tumor originated from a native kidney. The probability to develop renal failure was estimated to be more than 50% after the age of 36 years. Besides, neither genotype-phenotype correlation nor clinical predictive association with renal failure could be evidenced. These data reveal an unsuspected high incidence rate of the renal impairment outcome in OFD I syndrome. A systematic ultrasound (US) and renal function follow-up is therefore highly recommended for all OFD I patients.

Duplication of the mandibular primary dentition in orofacial-digital syndrome type IV.

Supernumerary teeth are commonly reported in patients with cleft lip and palate. The presence of a complete duplicate quadrant of teeth, however, is very rare. A patient with orofacial-digital syndrome type IV (Mohr-Majewski) presented with a duplication of the mandibular primary dentition in the right quadrant. Presence of decay and poor oral hygiene dictated intervention and removal of the supernumery teeth. A case report is presented.

The splice c.1815G>A variant in KIAA0586 results in a phenotype bridging short-rib-polydactyly and oral-facial-digital syndrome: A case report and literature review.

INTRODUCTION: KIAA0586 variants have been associated to short-rib thoracic dysplasia, an autosomal recessive skeletal ciliopathy characterized by a narrow thorax, short limbs, and radiological skeletal abnormalities. PATIENT CONCERNS: Patients 1 and 2 were two Roma Gypsy siblings presenting thoracic dysplasia and a combination of oral cavity anomalies. DIAGNOSIS: A custom NGS gene panel, including genes associated to skeletal ciliopathies, identified the homozygous KIAA0586 splicing variant c.1815G>A (p.Gln605Gln) in both siblings, confirming the clinical diagnosis of short-rib-polydactyly. INTERVENTION: Patients were transferred to neonatal intensive care unit and received life-support treatment. OUTCOMES: Patients 1 and 2 died after few hours and 1 month of birth, respectively, because of respiratory failure related with the disease. CONCLUSION: We report two patients affected by short-rib polydactyly syndrome and overlapping phenotype with oral-facial-digital syndrome associated with the c.1815G>A variant in KIAA0586, suggesting a quite peculiar genotype-phenotype correlation.

Blepharospasm and limb dystonia caused by Mohr-Tranebjaerg syndrome with a novel splice-site mutation in the deafness/dystonia peptide gene.

Mohr-Tranebjaerg syndrome (MTS) is an X-linked disorder characterized by childhood-onset progressive deafness, dystonia, spasticity, mental deterioration, and blindness. It is due to mutations in the deafness/dystonia peptide (DDP1) gene. We describe a sporadic 42-year-old man with MTS presenting with postlingual deafness, adult-onset progressive dystonia with marked arm tremor, mild spasticity of the legs, and visual disturbance due to a novel mutation (g to a transition at the invariant gt of the 5' splice donor site of exon 1) in the DDP1 gene. This case, and a review of previously reported cases, highlights a variety of potential diagnostic pitfalls in this condition.

Digitocutaneous dysplasia.

Digitocutaneous dysplasia is a rare X-linked dominant genetic syndrome characterized by multiple digital fibromas, atrophic plaques, dental anomalies, dysmorphic features, and bone anomalies. We report the case of a 2-year-old Mexican girl with this rare condition and discuss the clinical, histologic, and genetic features.

Surgically Induced Necrotizing Scleritis Following Strabismus Surgery Treated Successfully with Topical N-acetylcysteine in a Child with Congenital Fibrosis of Extraocular Muscles and Varadi Papp Syndrome.

INTRODUCTION: Surgically induced necrotizing scleritis (SINS) is a rare but serious disorder that can develop many years after strabismus surgery. It is generally treated with high-dose steroids or immunosuppression. CASE REPORT: We describe a patient with Varadi Papp syndrome and congenital fibrosis of the extraocular muscles, who developed surgically induced necrotizing scleritis a month after strabismus surgery and was successfully managed by oral vitamin C and topical N-acetylcysteine 10%. DISCUSSION: While SINS is conventionally treated with steroids/immunosuppression, a conservative approach may be tried in milder cases. The role of topical N-acetylcysteine in managing this complication needs to be explored.

Bimaxillary concomitant hypohyperdontia in a 10-year-old child.

Numerical anomalies, either addition or deletion, are quite a common findings in human dentition. However, it is extremely rare to find both hypodontia and hyperdontia simultaneously in the same individual. This condition is referred as concomitant hypohyperdontia (CHH). Aetiology of this condition is still obscure. The prevalence of CHH has been reported to be between 0.002% and 3.1%. This case report highlights a rare occurrence of bimaxillary CHH represented by the absence of both mandibular central incisors and presence of two supernumerary teeth in the maxillary anterior segment. The rarity of such condition of mixed hypodontia as well as hyperdontia in single human dentition prompted the author to report the case.