TaoMedAI/RareMedData huggingface dataset:
RNF13-related severe early-onset epileptic encephalopathy (ORPHA:544503)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by congenital microcephaly, infantile-onset epileptic encephalopathy, and profound developmental delay. Additional reported features include cortical visual impairment, sensorineural hearing loss, increased muscle tone, limb contractures, scoliosis, and dysmorphic features like midface hypoplasia, narrow forehead, short nose, narrowed nasal bridge, and small chin. Brain imaging may show thin corpus callosum and delayed myelination.
Roberts syndrome (ORPHA:3103)
Roberts syndrome (RBS) is characterized by pre- and postnatal growth retardation, severe symmetric limb reduction defects, craniofacial anomalies and severe intellectual deficit. SC phocomelia is a milder form of RBS.
Epidemiology
The prevalence and incidence are not known. Less than 150 cases have been described in the literature.
Clinical description
Upper limbs are more frequently and severely affected than lower limbs. The defect is mostly mesomelic with the radius being the most affected in the upper limbs, and the fibula in the lower limbs. The most severe defects result in phocomelia. Aplastic or hypoplastic thumbs, oligodactyly, clinodactyly or syndactyly can also occur. Craniofacial anomalies include microcephaly (more severe in males than in females), hypoplastic nasal alae, malar hypoplasia, hypertelorism, micrognathia, capillary hemangioma, exophthalmos, downslanting palpebral fissures, dysplastic or small ears, cloudy cornea or cataracts, and cleft lip and palate. There is a correlation between the degree of limb and facial malformations. Other malformations such as congenital heart defects, cystic kidney and large genitalia (enlarged phallus or clitoris), may occur. Severe intellectual deficit is observed in patients surviving the newborn period.
Etiology
The disease is caused by mutations in the ESCO2 gene (8p21.1), which encodes a protein belonging to the Eco1/Ctf7 family of acetyltransferases, involved in the establishment of sister chromatid cohesion during S phase. ESCO2 mutations lead to delayed cell division, increased cell death and impaired cell proliferation. The loss of progenitor cells during embryogenesis is likely responsible for the developmental defects observed in RBS.
Diagnostic methods
The diagnosis is based on clinical features and karyotyping (with a characteristic ``railroad track'' appearance of chromosomes due to repulsion of heterochromatic regions and premature centromere separation). Direct sequencing of the ESCO2 gene can confirm the diagnosis.
Differential diagnosis
Differential diagnoses include thalidomide embryopathy, and the Baller-Gerold, Cornelia de Lange and TAR syndromes (see these terms).
Antenatal diagnosis
When a previous child in the family is diagnosed with RBS and carries ESCO2 mutations, prenatal diagnosis can be performed through DNA analysis of chorionic villus samples. Otherwise, RBS may be suspected by observation of characteristic RBS anomalies at ultrasonography and can be confirmed by karyotyping.
Genetic counseling
The mode of transmission is autosomal recessive.
Management and treatment
Management includes surgical correction of facial malformations, surgical and/or orthopedic treatment of limb defects and management of the cognitive disabilities.
Prognosis
Prognosis is relatively unfavorable. High mortality in the newborn period or early childhood is due to cardiac or renal malformations.

                            Last update: 
                            September 2009


                            - Expert reviewer(s): 
                            Pr Sylvie MANOUVRIER-HANU
Robin sequence-oligodactyly syndrome (ORPHA:3104)
Robin sequence-oligodactyly syndrome is a rare, genetic, developmental defect during embryogenesis syndrome characterized by Robin sequence (i.e. severe micrognathia, retroglossia and U-shaped cleft of the posterior palate) associated with pre- and postaxial oligodactyly. Facial features can include a narrow face and narrow lower dental arch. Clinodactyly, absent phalanx, metacarpal fusions, and hypoplastic carpals have also been reported. There have been no further descriptions in the literature since 1986.
Rocky Mountain spotted fever (ORPHA:83311)
A rare, acquired, life-threatening, infectious disease due to the tick-borne bacteria Rickettsia rickettsii characterized by an acute onset of fever, malaise, and severe headache, variably accompanied by myalgia, anorexia, nausea, vomiting, abdominal pain, and photophobia, associating (2-5 days after fever onset) a typically erythematous, blanching or non-blanching, maculopapluar rash with petechiae, starting on the wrists and ankles and progressing centrifugally to the palms and soles and centripetally to the arms, legs and trunk. Additonal variable features may include conjunctivitis, mucosal ulcers, post-inflammatory hyperpigmentation, jaundice, pneumonia, hepatomegaly, renal failure, meningismus, amnesia, optic disc edema, and ocular arterial occlusion.
Roifman syndrome (ORPHA:353298)
A rare, genetic immuno-osseous dysplasia associated with pre- and post-natal growth retardation, retinopathy, microcephaly, intellectual disability and dysmorphic features.
Epidemiology
To date less than 20 cases have been reported worldwide in the scientific and medical literature.
Clinical description
Roifman syndrome is characterized by pre- and post-natal growth retardation, hypotonia, borderline to moderate intellectual disability, retinal dystrophy, spondyloepiphyseal dysplasia (epiphyseal dysplasia, epiphyses ossification delay, vertebral changes) and skeletal anomalies (brachydactyly, fifth finger clinodactyly), as well as humoral immunodeficiency, characterized by inability to generate specific antibodies and low circulating B-cells, suggestive of a partial block of B-cell proliferation and maturation. Craniofacial dysmorphism typically includes microcephaly, narrow palpebral fissures, prominent and long eyelashes, a narrow, tubular, upturned nose with hypoplastic alae nasi, long philtrum and thin upper lip. Eczema and mild limitation in hip flexion may be observed. One instance of hypogonadotrophic-hypogonadism and one instance of myocardial noncompaction were reported.
Etiology
Roifman syndrome is caused by bi-allelic mutations of RNU4ATAC (2q14.2), a gene encoding a small nuclear RNA involved in minor (U12) splicing. At least one mutation locates in the stem II region of RNU4ATAC. Mutations in the same gene also cause Taybi-Linder syndrome, a more severe disorder in which there are many overlapping features.
Diagnostic methods
Diagnosis is suggested based on the clinical, immune and radiological phenotype and confirmed by RNU4ATAC sequencing.
Differential diagnosis
Other syndromes that combine immunodeficiency and skeletal aberrations may be considered and include cartilage hair hypoplasia, primary bone dysplasias with micromelia, severe combined immunodeficiency due to adenosine deaminase deficiency, and Schimke immune-osseous dysplasia.
Antenatal diagnosis
There have been no reports of prenatal diagnosis to date.
Genetic counseling
Roifman syndrome is transmitted as an autosomal recessive trait. Genetic counseling should be offered to at risk families (where each parent is an unaffected carrier) informing them that there is a 25% risk of having an affected child at each pregnancy.
Management and treatment
Treatment is supportive only. Particular attention should be given to susceptibility to infections, growth and psychomotor development. Medical care and management should be provided according to recurrent infections and intellectual disability.
Prognosis
Prognosis appears to be good with no reported limitation of life expectancy. Infections can be severe and recurrent (pneumonia, septicemia, recurrent herpes reactivation, etc.).

                            Last update: 
                            March 2021


                            - Expert reviewer(s): 
                            Pr Patrick EDERY | ITHACA*


                                * European Reference Network
Rolandic epilepsy-paroxysmal exercise-induced dystonia-writer's cramp syndrome (ORPHA:163727)
A rare genetic epilepsy syndrome characterized by infantile or childhood onset of focal motor seizures remitting with age, as well as childhood onset of exercise-induced dystonia which often persists into adulthood. Additional reported features include nystagmus and postural tremor of the hands.
Rolandic epilepsy-speech dyspraxia syndrome (ORPHA:163721)
Rolandic epilepsy-speech dyspraxia syndrome is a rare, genetic epilepsy characterized by speech disorder (including a range of symptoms from dysarthria, speech dyspraxia, receptive and expressive language delay/regression and acquired aphasia to subtle impairments of conversational speech) and epilepsy (mostly focal and secondary generalized childhood-onset seizures, sometimes with aura). Mild to severe intellectual disability may also be observed.
Rombo syndrome (ORPHA:3110)
Rombo syndrome is characterized by vermiculate atrophoderma, milia, hypotrichosis, trichoepitheliomas, peripheral vasodilation with cyanosis and basal cell carcinomas.
Epidemiology
It has been described in four generations of one family and in two additional sporadic cases.
Clinical description
The skin lesions become visible between 7 and 10 years of age and are most pronounced on the face. Basal cell carcinomas are frequent and develop at around 35 years of age.
Etiology
The etiology remains unknown.

                            Last update: 
                            September 2009
Rosaï-Dorfman disease (ORPHA:158014)
A rare non-Langerhans cell histiocytosis characterized by infiltration of lymph nodes or extranodal tissues by non-malignant histiocytes displaying emperipolesis, a non-destructive phagocytosis of lymphocytes or erythrocytes. Most typical presentation is as a massive cervical lymphadenopathy in adolescents and young adults. Most frequent sites of extranodal disease are skin, soft tissue, bones, paranasal sinuses, orbit, salivary glands, and central nervous system. Symptoms are related to mass effect in the affected organs.
Rosette-forming glioneuronal tumor (ORPHA:251975)
Rosette-forming glioneuronal tumor is a rare mixed neuronal-glial tumor characterized by the presence of uniform, rosette- (or pseudorosette-) forming neurocytes with an astrocytic component, together creating a biphasic pattern. It can present with signs of raised intracranial pressure (headache, vomiting, papilledema), hydrocephalus, seizures, ataxia and visual disturbances, or can be diagnosed incidentally in asymptomatic patients. The tumor usually arises in the midline, involving the fourth ventricle or the cerebellum.
Rothmund-Thomson syndrome type 1 (ORPHA:221008)
Rothmund-Thomson syndrome type 1 is a subform of Rothmund-Thomson syndrome (RTS; see this term) presenting with a characteristic facial rash (poikiloderma) and frequently associated with short stature, sparse scalp hair, sparse or absent eyelashes and/or eyebrows, and rapidly progressive bilateral juvenile cataracts. In contrast to RTS2 (see this term), patients with RTS1 do not appear to have an increased risk of developing cancer.
Epidemiology
Around 300 cases of RTS have been reported in the literature so far, with RTS1 accounting for around one-third of cases.
Etiology
RTS is transmitted in an autosomal recessive manner and although mutations in the RECQL4 gene have been found in patients with the RTS2 subform (see this term), the etiology of RTS1 remains unknown.

                            Last update: 
                            February 2010
Rothmund-Thomson syndrome type 2 (ORPHA:221016)
Rothmund-Thomson syndrome type 2 is a subform of Rothmund-Thomson syndrome (RTS; see this term) presenting with a characteristic facial rash (poikiloderma) and frequently associated with short stature, sparse scalp hair, sparse or absent eyelashes and/or eyebrows, congenital bone defects and an increased risk of osteosarcoma in childhood and squamous cell carcinoma later in life.
Epidemiology
Around 300 cases of RTS have been reported in the literature so far, with RTS2 accounting for around two-thirds of the cases.
Clinical description
The skeletal abnormalities may be overt (such as frontal bossing, saddle nose and congenital radial ray defects), and/or subtle anomalies visible only by radiographic analysis.
Etiology
RTS is transmitted as an autosomal recessive trait and RTS2 is caused by homozygous or compound heterozygous mutations in the RECQL4 gene (8q24.3), whereas the etiology of RTS1 (see this term) remains unknown.

                            Last update: 
                            February 2010
Roussy-Lévy syndrome (ORPHA:3115)
A rare demyelinating hereditary motor and sensory neuropathy characterized by prominent gait ataxia, pes cavus, tendon areflexia, distal limb weakness, tremor in the upper limbs, distal sensory loss, kyphoscoliosis, and progressive muscle atrophy. The disease becomes symptomatic in infancy or childhood, mode of inheritance is autosomal dominant.
Rubella panencephalitis (ORPHA:83616)
A rare chronic encephalitis developing up to several years after congenital rubella virus infection or rubella infection in childhood, characterized by slowly progressive, wide-spread neurological symptoms, like cognitive decline, cerebellar ataxia, spasticity, and seizures, amongst others. Progredient deterioration of the neurological disease eventually leads to the death of the patient.
Ruvalcaba syndrome (ORPHA:3121)
Ruvalcaba syndrome is an extremely rare malformation syndrome, described in less than 10 patients to date, characterized by microcephaly with characteristic facies (downslanting parpebral fissures, microstomia, beaked nose, narrow maxilla), very short stature, narrow thoracic cage with pectus carinatum, hypoplastic genitalia and skeletal anomalies (i.e. characteristic brachydactyly and osteochondritis of the spine) as well as intellectual and developmental delay.
Saccharopinuria (ORPHA:3124)
A rare autosomal recessive disorder of the lysine catabolism characterized by elevated levels of lysine in the cerebrospinal fluid and blood with variable degrees of saccharopinuria. Some patients present with neurological symptoms such as seizures, spastic diplegia, mild psychomotor delay, intellectual deficit, and behavioral difficulties. However, current findings suggest no causal association between isolated hyperlysinemia and neurological symptoms.
Sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome (ORPHA:397927)
Sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome is a rare, genetic, neural tube defect malformation syndrome characterized by sacral agenesis and abnormal vertebral body ossification with normal vertebral arches associated with notochord canal persistence on ultrasonography. Additional findings include bilateral clubfoot, oligohydramnios, single umbilical artery and, in some, increased nuchal translucency.
Sagliker syndrome (ORPHA:300493)
A rare bone disease characterized by secondary hyperparathyroidism in patients with chronic renal failure, caused by improper treatment in the early stages of the disease with retention of phosphorus, vitamin D deficiency, and disturbed calcium-phosphorus metabolism, which result in increased parathyroid hormone levels. Patients present with short stature, severe changes of the skull and jaws as well as other skeletal deformities, dental anomalies, ''brown tumors'' in the mouth, hearing loss, and neuropsychiatric disorders.
Saldino-Mainzer syndrome (ORPHA:140969)
Saldino-Mainzer syndrome is characterised by the association of renal disease, retinal pigmentary dystrophy, cerebellar ataxia and skeletal dysplasia.
Epidemiology
Around 10 cases have been described in the literature so far.
Clinical description
Mild to moderate short stature has also been reported. Radiologic studies reveal shortened phalanges with cone-shaped epiphysis. Femoral epiphyseal and metaphyseal anomalies are common.
Genetic counseling
The syndrome is transmitted as an autosomal recessive trait.

                            Last update: 
                            July 2008
Salivary gland type cancer of the breast (ORPHA:213557)
Salivary gland type cancer of the breast describes a group of uncommon neoplasms, usually seen in the salivary glands but occurring in the breast, with a variable clinicopathologic spectrum and divided into those with myoepithelial differentiation and those without. This group includes mammary adenoid cystic carcinoma, adenoid cystic carcinoma (see this term), mucoepidermoid carcinoma, acinic cell carcinoma, polymorphous low-grade adenocarcinoma and oncocytic carcinoma.
Sandifer syndrome (ORPHA:71272)
Sandifer syndrome is a paroxysmal dystonic movement disorder occurring in association with gastro-oesophageal reflux, and, in some cases, hiatal hernia.
Epidemiology
The prevalence is unknown.
Clinical description
Onset usually occurs during infancy or early childhood. The dystonic movements are characterised by abnormal posturing of the head and neck (torticollis) and severe arching of the spine. Episodes usually last for between 1-3 minutes and can occur up to 10 times a day, although they are usually associated with the ingestion of food. Vomiting, poor feeding, anaemia, epigastric discomfort, haematemesis and abnormal eye movements have also been reported. Reflux oesophagitis is common.
Etiology
The dystonic movements are clearly associated with gastro-oesophageal reflux but the pathophysiological mechanism is not clearly understood. Several studies have indicated that the dystonic posturing is a pathological reflex triggered in response to abdominal pain caused by gastroesophageal reflux and oesophagitis. Although conflicting results have been obtained, some authors have suggested that the dystonic posture provides relief from abdominal pain.
Diagnostic methods
Sandifer syndrome is diagnosed on the basis of the association of gastro-oesophageal reflux with the characteristic movement disorder. Neurological examination is usually normal.
Differential diagnosis
However, in the absence of clear indications of gastro-oesophageal reflux, misdiagnosis as infantile spasms, epilepsy or paroxysmal dystonia is common.
Management and treatment
Early diagnosis of the syndrome is essential, as effective treatment of the gastro-oesophageal reflux (by pharmacological therapy or surgical intervention) leads to resolution of the movement disorder.
Prognosis
The prognosis for patients is good.

                            Last update: 
                            March 2007
Sanjad-Sakati syndrome (ORPHA:2323)
Sanjad-Sakati syndrome (SSS), also known as hypoparathyroidism - intellectual disability-dysmorphism, is a rare multiple congenital anomaly syndrome, mainly occurring in the Middle East and the Arabian Gulf countries, characterized by intrauterine growth restriction at birth, microcephaly, congenital hypoparathyroidism (that can cause hypocalcemic tetany or seizures in infancy), severe growth retardation, typical facial features (long narrow face, deep-set eyes, beaked nose, floppy and large ears, long philtrum, thin lips and micrognathia), and mild to moderate intellectual deficiency. Ocular findings (i.e. nanophthalmos, retinal vascular tortuosity and corneal opacification/clouding) and superior mesenteric artery syndrome have also been reported. Although SSS shares the same locus with the autosomal recessive form of Kenny-Caffey syndrome (see this term), the latter differs from SSS by its normal intelligence and skeletal features.
Sarcocystosis (ORPHA:54368)
A rare parasitic disease characterized by infection with sarcocystis species with humans as definitive (intestinal sarcocystosis) or aberrant intermediate (muscular sarcocystosis with development of sarcocysts in myocytes of skeletal, cardiac, and smooth muscle) host. Enteric infection is often mild or asymptomatic but may cause symptomatic enteritis with nausea, abdominal pain, diarrhea, and vomiting. Symptoms of muscular sarcocystosis include fever, fatigue, headache, cough, myalgia, and arthralgia, among others, with the possibility of a long-lasting, waxing and waning course.
Sarcosinemia (ORPHA:3129)
A rare inborn error of metabolism characterized by increased concentrations of sarcosine in plasma and urine due to sarcosine dehydrogenase deficiency. The condition is considered benign and not associated with any specific clinical phenotype. Mode of inheritance is autosomal recessive.
SATB2-associated syndrome (ORPHA:576278)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by moderate to severe developmental delay/intellectual disability with absent or limited speech development, various behavioral problems (including autistic features, hyperactivity, or aggressiveness), and craniofacial anomalies such as long face, high and prominent forehead, bulbous nose with low-hanging columella, thin vermillion of the upper lip, palatal (cleft palate, high-arched palate, and bifid uvula) and dental (abnormal upper incisors) abnormalities, and micrognathia. Hypotonia and feeding difficulties are frequent. Other supportive findings may include skeletal anomalies with low bone density and abnormal brain imaging.
Satoyoshi syndrome (ORPHA:3130)
Satoyoshi syndrome is a rare, multisystemic autoimmune disease mainly characterized by intermittent painful muscle spasms, alopecia (totalis or universalis in most cases) and long-lasting diarrhea that could lead to malnutrition, growth retardation, and amenorrhea. Secondary bone deformities and various endocrine anomalies may also be associated. Antinuclear antibodies are reported in many cases.
Say-Barber-Miller syndrome (ORPHA:3132)
A rare multiple congenital anomalies/dysmorphic syndrome characterized by microcephaly, developmental delay and intellectual disability, postnatal growth retardation, dysmorphic craniofacial features (including sloping forehead, beaked nose, large and protruding ears, micrognathia, high-arched palate, and craniosynostosis), immunologic abnormalities with transient hypogammaglobulinemia in infancy and defective chemotaxis leading to recurrent infections, as well as autoimmune/autoinflammatory phenomena. Skeletal anomalies and hypogonadism have also been reported.
Scalp defects-postaxial polydactyly syndrome (ORPHA:1003)
A rare syndrome with limb malformations as a major feature characterized by congenital scalp defects and postaxial polydactyly type A. There is a wide variability of expression, with some patients showing only one of the typical manifestations. There have been no further descriptions in the literature since 1985.
SCALP syndrome (ORPHA:370052)
SCALP syndrome is a rare skin disease characterized by the association of sebaceous nevus and aplasia cutis congenita (usually on the scalp and face) in conjunction with limbal dermoid of the eye, a giant congenital melanocytic nevus and variable central nervous system abnormalities, including seizures, hydrocephalus, neurocutaneous melanosis, arachnoid cysts, and diffuse unilateral hemisphere enlargement.
Scalp-ear-nipple syndrome (ORPHA:2036)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by aplasia cutis congenita of the scalp, breast anomalies ranging from hypothelia or athelia to amastia, and anomalies of the external ears. Variable clinical characteristics include nail and dental anomalies, syndactyly and camptodactyly of fingers and/or toes, sparse or absent secondary sexual hair, renal malformations, and facial dysmorphism. Cases with severe hypotonia and developmental delay have been reported.