TaoMedAI/RareMedData huggingface dataset:
Central cloudy dystrophy of François (ORPHA:98972)
Central cloudy dystrophy of François is a very rare form of stromal corneal dystrophy (see this term) characterized by polygonal or rounded stromal opacities surrounded by clear tissue, and generally no effect on vision.
Epidemiology
The prevalence of this form of corneal dystrophy is unknown.
Clinical description
Lesions generally appear in the first decade of life; subjects with the condition are mostly asymptomatic. The course of the disease is non-progressive.
Etiology
Etiology is unknown.
Differential diagnosis
Corneal changes are very similar to Vogt posterior crocodile shagreen, a corneal degenerative disease.
Genetic counseling
Autosomal dominant inheritance has been reported.

                            Last update: 
                            May 2012


                            - Expert reviewer(s): 
                            Dr Gordon KLINTWORTH
Central congenital hypothyroidism (ORPHA:226298)
Central or secondary congenital hypothyroidism is a type of permanent congenital hypothyroidism (see this term) characterized by permanent thyroid hormone deficiency that is present from birth and secondary to a disorder in the thyroid-stimulating hormone (TSH) - thyrotropin-releasing hormone (TRH) system.
Epidemiology
Prevalence is unknown.
Clinical description
The clinical manifestations are often subtle, probably as a result of trans-placental passage of some maternal thyroid hormone or due to the fact that many infants have some thyroid production of their own. More specific symptoms and signs often do not develop until several months of age. Common clinical features and signs include decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice, myxedematous facies, large fontanels (especially posterior), macroglossia, a distended abdomen with umbilical hernia, and hypotonia. Goiter is always absent. Slow linear growth and developmental delay are usually apparent by 4-6 months of age. Without treatment central hypothyroidism results in intellectual deficit and short stature.
Etiology
Central hypothyroidism usually results from defects of TSH production and is often part of a disorder causing congenital hypopituitarism (see this term), in which case the clinical signs may also include septo-optic dysplasia or cleft lip and/or palate as well as other signs of hypopituitarism, or part of a larger genetic syndrome such as pituitary stalk interruption syndrome (see this term). Mutations in genes regulating pituitary gland development including HESX1, LHX3, LHX4, POU1F1 and PROP1 (3p21.2-p21.1, 9q34.3, 1q25, 3p11 and 5q) may also cause central hypothyroidism. Central hypothyroidism may also result from isolated TSH deficiency (see this term), which is transmitted in an autosomal recessive manner and is caused by mutations in the TSHB subunit gene (1p13), or from TRH resistance (see this term) caused by mutations in the TRH receptor gene (TRHR; 8q23).

                            Last update: 
                            August 2010


                            - Expert reviewer(s): 
                            Dr Stephen LAFRANCHI  - Dr Maynika RASTOGI
Central core disease (ORPHA:597)
Central core disease (CCD) is an inherited neuromuscular disorder characterised by central cores on muscle biopsy and clinical features of a congenital myopathy.
Epidemiology
Prevalence is unknown.
Clinical description
CCD typically presents in infancy with hypotonia and motor developmental delay and is characterized by predominantly proximal weakness, pronounced in the hip girdle. Orthopaedic complications are common and malignant hyperthermia susceptibility (MHS) is a frequent complication.
Etiology
CCD and MHS are allelic conditions, both caused by (predominantly dominant) mutations in the skeletal muscle ryanodine receptor (RYR1) gene, encoding the principal skeletal muscle sarcoplasmic reticulum calcium release channel (RyR1). Altered excitability and/or changes in calcium homeostasis within muscle cells due to mutation-induced conformational changes in the RyR protein are considered to be the main pathogenetic mechanism(s).
Diagnostic methods
The diagnosis of CCD is based on the presence of suggestive clinical features and central cores on muscle biopsy. Muscle MRI may show a characteristic pattern of selective muscle involvement and aid the diagnosis in cases with equivocal histopathological findings. Mutational analysis of the RYR1 gene may provide genetic confirmation of the diagnosis.
Management and treatment
Management is mainly supportive and has to anticipate susceptibility to potentially life-threatening reactions to general anaesthesia. Further evaluation of the underlying molecular mechanisms may provide the basis for future rational pharmacological treatment.
Prognosis
In the majority of patients, weakness is static or only slowly progressive, with a favourable long-term outcome.

                            Last update: 
                            May 2007


                            - Expert reviewer(s): 
                            Dr Heinz JUNGBLUTH
Central neurocytoma (ORPHA:73256)
Central neurocytoma is a very rare brain tumor of young adults (over 100 cases reported worldwide). It is typically found in the lateral ventricles and occasionally in the third ventricle. Symptoms are those of increased intracranial pressure: headache, nausea and vomiting, drowsiness, vision problems and mental changes. Total removal of the tumor is the therapy of choice. Post-operative prognosis is generally good.
Central polydactyly (ORPHA:295004)
A rare congenital limb malformation characterized by complete or partial duplication of one of the three middle digits in a hand or foot. It most commonly affects the fourth digit. The malformation may be unilateral or bilateral and can occur as an isolated defect or in association with other anomalies.
Central retinal vein occlusion (ORPHA:411527)
A rare retinal vasculopathy characterized by impaired venous return from the retinal circulation due to an occlusion occurring within or posterior to the optic nerve head. The clinical presentation is variable and may range from asymptomatic to an abrupt and profound loss of vision. Complications causing visual loss include macular edema, macular ischemia, optic neuropathy, vitreous hemorrhage, tractional retinal detachment, and in more severe cases extensive capillary non-perfusion with a high risk of neovascular glaucoma.
Central serous chorioretinopathy (ORPHA:443079)
A rare, acquired, choroidal disorder characterized by subretinal detachment in the macular área and leakage of fluid under the retina that accumulates under the central macula. Symptoms tend to include blurred or distorted vision (metamorphopsia), moderate dyschromatopsia, relative central scotoma, hypermetropization, micropsia and reduced contrast sensitivity. A blurred or gray spot in the central visual field is common when the retina is detached.
Centrifugal lipodystrophy (ORPHA:90156)
Centrifugal lipodystrophy is a rare, acquired, localized lipodistrophy characterized by single or, occasionally, multiple, centrifugally progressive, asymptomatic to sometimes mildly tender, hypopigmented, lipoatrophic skin depressions with weakly erymatheous inflammatory borders, typically associated with regional ipsilateral lymph nodes swelling. Lesions typically occur on lower trunk (in particular groin and abdomen region), followed by upper trunk (axilla and neighboring regions) and, rarely, neck and head. It is usually not associated with systemic disease and is typically self-resolving.
Centronuclear myopathy (ORPHA:595)
A rare group of inherited neuromuscular disorders characterized by clinical features of a congenital myopathy and centrally placed nuclei on muscle biopsy. The clinical picture and other histologic features varies according to gene involved and mode of inheritance.
Epidemiology
The exact prevalence and incidence of this group of diseases are unknown. For the X-linked form (XLMTM1) the incidence is estimated at 1/50,000 male birth.
Clinical description
These congenital myopathies are characterized by generalized muscle weakness that can range from mild to severe. Symptoms are often present at birth in the severe forms, but may first develop at any point during life, although onset in adulthood is unusual. In the severe forms the common symptoms include hypotonia, feeding difficulties and respiratory distress. Extraocular muscle involvement is also common in all forms. Other common signs and symptoms include delayed motor milestones, facial weakness and ptosis.
Etiology
Centronuclear myopathies (CNMs) are genetically widely heterogeneous and have been attributed mainly to X-linked recessive mutations in MTM1 (Xq28), encoding myotubularin 1 (X-linked centronuclear myopathy), autosomal-dominant mutations in DNM2( 19p13.2), encoding dynamin-2, autosomal dominant or recessive mutations in BIN1 (2q14.3), encoding myc box-dependent-interacting protein 1, and autosomal-recessive mutations in RYR1 (19q13.2), encoding the skeletal muscle ryanodine receptor, and in TTN (2q31.2), encoding titin. More recently, there have also been reports on peculiar CNM phenotypes related to autosomal recessive mutations in SPEG (2q35), encoding the striated muscle preferentially expressed protein kinase, and mutations in CCDC78 (16p13.3), encoding the coiled-coil domain-containing protein-78.
Diagnostic methods
Diagnosis is based on typical histological findings of central nuclei, hypotrophy and predominance of type I fibers.
Differential diagnosis
The main differential diagnoses include other forms of congenital myopathies or other neuromuscular conditions with severe neonatal hypotonia.
Antenatal diagnosis
In familial cases, prenatal diagnosis can be performed if the genetic background is known.
Genetic counseling
Genetic counseling should be offered to all patients and families in whom a diagnosis of CNM has been made.
Management and treatment
Management of CNM requires a multidisciplinary approach. No specific therapy exists yet but different therapeutic strategies are under investigation.
Prognosis
The prognosis of this group of disease is variable. Whereas the XLMTM1 is often fatal in infancy, dominant forms due to DNM2 mutations and some cases of the recessive BIN1-related form appear to be associated with a globally more favourable prognosis.

                            Last update: 
                            March 2020


                            - Expert reviewer(s): 
                            Pr Enrico BERTINI  - Dr Adele D'AMICO  - Pr Fabiana FATTORI
Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (ORPHA:504476)
A rare slowly progressive autosomal recessive syndromic cerebellar ataxia characterized by late-onset cerebellar dysfunction (including gait and limb ataxia, nystagmus, and dysarthria), bilateral vestibulopathy (abnormal vestibulo-ocular reflex), and axonal sensory neuropathy. Variable features may include chronic cough and autonomic dysfunction. Brain imaging usually shows cerebellar atrophy.
Cerebellar ataxia, Cayman type (ORPHA:94122)
A rare, autosomal recessive, congenital, cerebellar ataxia disorder characterized by hypotonia from birth, marked psychomotor delay and prominent cerebellar dysfunction (manifesting with nystagmus, intention tremor, dysarthria, ataxic gait and truncal ataxia), described in an isolated population of the Grand Cayman Island. Cerebellar hypoplasia, observed on CT scan, may be associated.
Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome (ORPHA:1171)
A rare autosomal dominant neurological disorder characterized by early onset cerebellar ataxia, associated with areflexia, progressive optic atrophy, sensorineural deafness, a pes cavus deformity, and abnormal eye movements.
Cerebellar ataxia-ectodermal dysplasia syndrome (ORPHA:1174)
A rare syndromic cerebellar ataxia characterized by hypodontia and sparse hair in combination with cerebellar ataxia and normal intelligence. Imaging demonstrates a cerebellar atrophy.
Cerebellar ataxia-hypogonadism syndrome (ORPHA:1173)
Cerebellar ataxia-hypogonadism syndrome is a very rare autosomal recessive neurodegenerative disorder characterized by the combination of progressive cerebellar ataxia with onset from early childhood to the fourth decade, and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). Cerebellar ataxia-hypogonadism syndrome belongs to a clinical continuum of neurodegenerative disorders along with clinically overlapping disorders such as ataxia-hypogonadism-choroidal dystrophy syndrome (see this term).
Cerebellar hypoplasia-tapetoretinal degeneration syndrome (ORPHA:2246)
Cerebellar hypoplasia-tapetoretinal degeneration syndrome is a rare syndrome with a cerebellar malformation as a major feature characterized by cerebellar hypoplasia, bilateral retinal pigmentary changes, intellectual disability that can range from mild to moderate and pronounced language development delay. It presents with early developmental delay, central and peripheral non-progressive visual impairment or asymptomatic retinal changes, hypotonia, non-progressive ataxia and nystagmus.
Cerebellar liponeurocytoma (ORPHA:251931)
Cerebellar liponeurocytoma (cLPN) is a rare slow growing neuronal tumor seen more frequently in females than males, occurring most commonly in the cerebellum but occasionally in the supratentorial compartment or the fourth ventricle and presenting in the 4th to 6th decade of life with symptoms of dizziness, headache and gait instability. It often has a high rate of local recurrence.
Cerebellar-facial-dental syndrome (ORPHA:444072)
A rare, autosomal recessive, multiple congenital anomalies/dysmorphic syndrome characterized mainly by developmental delay, variable intellectual disability, microcephaly, cerebellar hypoplasia, dysmorphic features (central incisors macrodontia and slender fingers), short stature and variable congenital anomalies.
Epidemiology
To date, ten patients carrying biallelic BRF1 variants have been reported in the literature.
Clinical description
The clinical features of the syndrome include developmental delay and intellectual disability. Congenital microcephaly is present in all patients with occipital frontal circumference recorded and with progressive deceleration. Postnatal growth retardation occurred in all patients with height last evaluation between -2.5 and -5 SD. The most constant dysmorphic features include central incisors macrodontia and slender fingers. Laryngomalacia, tracheomalacia, congenital heart defect, sensorineural hearing impairment and inner ear malformation have been reported. Brain malformations, as detected on magnetic resonance imaging, may include cerebellar hypoplasia, corpus callosum hypoplasia and, more variably, enlarged cisterna magna and enlarged lateral ventricles.
Etiology
The disorder is due to biallelic variants in the BRF1 (14q32.33) gene; the pathogenic variants reported are missense variants, with only one frameshift mutation identified. All variants affect protein residues located within the cyclin 2 protein domain.
Diagnostic methods
All patients reported had been diagnosed by next generation sequencing.
Differential diagnosis
The disorder is distinguished from other intellectual disability syndromes mainly by short stature and progressive microcephaly. Prominent upper incisors is a remarkable sign.
Antenatal diagnosis
Where the mutation has been identified previously in a proband, prenatal molecular genetic testing could be offered.
Genetic counseling
The pattern of inheritance is autosomal recessive. Families with an affected child should be counselled that there is a recurrence risk of 25% for each pregnancy.
Management and treatment
Standard management is indicated for intellectual disability and postnatal growth retardation. Echocardiography, abdominal ultrasound and hearing evaluation is recommended at birth. Surveillance should include frequent monitoring of growth and development. Regular ophthalmological follow up is recommended.
Prognosis
Patients reported with poor prognosis are related to complex heart defects.

                            Last update: 
                            October 2020


                            - Expert reviewer(s): 
                            Dr Irene VALENZUELA PALAFOLL | ITHACA*


                                * European Reference Network
Cerebral arteriovenous malformation (ORPHA:46724)
Cerebral arteriovenous malformation (AVM) is a congenital malformative communication between the veins and the arteries in the brain in the form of a nidus, an anatomical structure composed of dilated and tangled supplying arterioles and drainage veins with no intervening capillary bed, that can be asymptomatic or cause, depending on the location and the size of the AVM, headaches of varying severity, generalized or focal seizures, focalneurological defects (weakness, numbness, speech difficulties, vision loss) or potentially fatal intracranial hemorrhage in case the AVM ruptures.
Cerebral sinovenous thrombosis (ORPHA:329217)
A rare, potentially life-threatening, circulatory system disease characterized by variable signs and symptoms which may include headache, seizures, altered mental status, intracranial hypertension and cavernous sinus syndrome, among others.
Cerebral visual impairment (ORPHA:447788)
A rare neurologic disease characterized by significant visual dysfunction that cannot be explained by ocular abnormalities alone and is due to damage to post-chiasmatic visual pathways and structures during early perinatal development. Signs and symptoms include decreased visual acuity, visual field defects, and impairments in visual processing and attention.
Cerebrofacial arteriovenous metameric syndrome type 1 (ORPHA:141194)
A rare subtype of cerebrofacial arteriovenous metameric syndrome characterized by unilateral arteriovenous malformations involving the hypothalamus and nasal region (medial prosencephalic group). The condition manifests in childhood. Common presenting signs and symptoms are progressive neurological deficit, hemorrhage, and cosmetic complaints like facial asymmetry.
Cerebrofacial arteriovenous metameric syndrome type 3 (ORPHA:141199)
A rare subtype of cerebrofacial arteriovenous metameric syndrome characterized by unilateral arteriovenous malformations involving the cerebellum, pons, and mandible (lateral rhombencephalic group). The condition manifests in childhood. Common presenting signs and symptoms are progressive neurological deficit, hemorrhage, and cosmetic complaints like facial asymmetry.
Cerebrofacioarticular syndrome (ORPHA:314679)
Cerebrofacioarticular syndrome is a rare multiple congenital anomalies syndrome characterized by mild to severe intellectual disability, a distinctive facial gestalt (blepharophimosis, maxillary hypoplasia, telecanthus, microtia and atresia of the external auditory meatus) as well as skeletal and articular abnormalities (e.g. camptodactyly of the fingers, cutaneous syndactyly, talipes equinovarus, flexion contractures of the proximal interphalangeal joints, hip or elbow subluxation, joint laxity). Affected individuals also present neonatal hypotonia, variable respiratory manifestations, chronic feeding difficulties and gray matter heterotopia.
Cerebrofaciothoracic dysplasia (ORPHA:1394)
Cerebro-facio-thoracic dysplasia or Pascual-Castroviejo syndrome type 1 is a rare syndrome characterized by facial dysmorphism, intellectual deficit and costovertebral abnormalities.
Epidemiology
To date, 13 cases have been reported in the literature.
Clinical description
Dysmorphic features include brachycephaly, hypertelorism, broad nasal bridge, large philtrum, triangular-shaped mouth and micrognathia. There is often synophris and a low hair line on the back. Costovertebral abnormalities are always present: short, bifid or fused ribs, bony bridges joining the posterior arches in some ribs, hemi vertebrae. Intellectual deficit is constant but the severity varies and patients also have cerebral abnormalities: cortical atrophy, hypoplasia of the corpus callosum and cerebellar vermis.
Etiology
It is most likely that the condition is hereditary, transmitted as an autosomal recessive trait.
Antenatal diagnosis
Antenatal diagnosis is possible by ultrasonographic monitoring for cerebral, costal or vertebral malformations.

                            Last update: 
                            January 2010
Cerebrooculonasal syndrome (ORPHA:66625)
Cerebro-oculo-nasal syndrome is a multisystem malformation syndrome that has been reported in about 10 patients. The clinical features include bilateral anophthalmia, abnormal nares, central nervous system anomalies, and neurodevelopmental delay.
Clinical description
Additional features include brachycephaly (the nose may have a proboscis-like appearance) and other facial anomalies such as large forehead, flat supraorbital ridges, ocular hypertelorism, epicanthic folds, downslanting palpebral fissures, sparse and medially absent eyebrows, sparse eyelashes, malar hypoplasia, large philtrum, high-arched palate possibly associated with atypical cleft lip and a single maxillary central incisor, posteriorly rotated ears with hypoplastic tragus and large conchae. Non facial anomalies have also been reported: postaxial polydactyly, genital hypoplasia.
Antenatal diagnosis
No case of prenatal diagnosis has been reported.
Genetic counseling
All cases reported so far have been sporadic, suggesting that the syndrome may be due to a new dominant mutation.

                            Last update: 
                            March 2006
Cernunnos-XLF deficiency (ORPHA:169079)
Cernunnos-XLF deficiency is a rare form of combined immunodeficiency characterized by microcephaly, growth retardation, and T and B cell lymphopenia.
Epidemiology
Prevalence is unknown. To date, five cases have been reported.
Clinical description
Patients present in childhood with growth retardation, microcephaly, uro-genital and bone malformations, dysmorphic features, including ''bird-like'' facial dysmorphism, and features of combined immunodeficiency including recurrent opportunistic, viral and bacterial infections. Some patients may also present with autoimmune cytopenia (anemia and thrombocytopenia). Patients share several clinical features with Nijmegen breakage syndrome and LIG 4 deficiency (see these terms).
Etiology
This disease is caused by mutations in the NHEJ1 (or Cernunos) gene (2q35). The resulting defect of Cernunnos/XLF, a core protein of the non-homologous end-joining (NHEJ) pathway, affects the major mechanism of DNA double-strand break repair.
Diagnostic methods
Diagnosis is based on the combination of clinical features with evidence of B and T cell lymphocytopenia with normal levels of natural killer (NK) cells. Fibroblasts also exhibit increased radiosensitivity.
Differential diagnosis
Differential diagnoses include Nijmegen breakage syndrome and LIG4 syndrome (see these terms).
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
Treatment is based on antibiotic treatment of infections, immunoglobulin replacement, antiviral prophylaxis and allogeneic hematopoietic stem-cell transplantation (HSCT). Radiotherapy as part of conditioning regimens should be avoided. Reduced intensity conditioning regimens are favored.
Prognosis
Without treatment, the immunodeficiency may result in severe infection, sepsis and early death.

                            Last update: 
                            July 2012


                            - Expert reviewer(s): 
                            Pr Andrew GENNERY
Cerulean cataract (ORPHA:98989)
A type of hereditary congenital cataract, distinguished by bluish and white opacifications in the superficial layers of the fetal lens nucleus and adult lens nucleus, and characterized by reduced visual acuity in childhood, eventually necessitating extraction of the lens.