TaoMedAI/RareMedData huggingface dataset:
Granulomatous slack skin (ORPHA:33111)
Granulomatous slack skin (GSS) is a variant of mycosis fungoides (MF; see this term), a form of cutaneous T-cell lymphoma, and is characterized by the presence of circumscribed areas of pendulous lax skin.
Epidemiology
Less than 50 cases have been reported in the literature so far. GSS predominantly affects males (sex ratio: 2.9:1).
Clinical description
Onset usually occurs in adulthood. The disease is characterized by the slow development of large areas of pendulous, lax skin in the major skin folds (axillae and groins). Although GSS is considered as a variant of MF, an association with Hodgkin lymphoma was observed in approximately one-third of the reported patients.
Etiology
The etiology is unknown. A chromosomal translocation, t(3;9)(q12;p24), was found in one case.
Diagnostic methods
The diagnosis is based on typical clinical findings and on histologic features revealing a dermal infiltrate of T-cells (with a CD3+, CD4+ and CD8- phenotype) with granulomatous features and the presence of multinucleated giant cells. Molecular analyses reveal a monoclonal rearrangement of the T-cell receptor genes.
Differential diagnosis
Acquired cutis laxa (see this term) can be differentiated from granulomatous slack skin by histological examination.
Management and treatment
No reliable treatment exists. Surgical excision of the pendulous skin folds is usually performed, but is only palliative and recurrence is the rule. Radiotherapy has been used in some patients. A variety of other therapies (mostly treatments for MF) have been tested in anecdotal cases with variable success.
Prognosis
Most patients have an indolent clinical course.

                            Last update: 
                            June 2009


                            - Expert reviewer(s): 
                            Pr Lorenzo CERRONI
Grayson-Wilbrandt corneal dystrophy (ORPHA:293375)
Grayson-Wilbrandt corneal dystrophy (GWCD) is an extremely rare form of corneal dystrophy characterized by variable patterns of opacification in the Bowman layer of the cornea which extend anteriorly into the epithelium with decreased to normal visual acuity.
Epidemiology
Prevalence of this form is unknown and the existence of GWCD as a distinct entity is questionable. Only one incompletely studied family has been reported.
Clinical description
Onset is in the first to second decade of life. Patients develop painful erosions that are less severe than those in Reis-Bücklers corneal dystrophy and Thiel-Behnke corneal dystrophy (see these terms). Visual acuity is normal or sometimes slightly decreased. The condition has a progressive course.
Etiology
The etiology is unknown but is thought to be genetic.
Diagnostic methods
On slit-lamp examination, Bowman layer demonstrates variable patterns of opacification from diffuse mottling to diffuse gray-white opacities, which extend anteriorly into the epithelium. The cornea between the deposits is clear.
Genetic counseling
An autosomal dominant pattern of inheritance has been reported.
Management and treatment
A superficial keratectomy or penetrating keratoplasty can improve vision.

                            Last update: 
                            May 2012


                            - Expert reviewer(s): 
                            Dr Gordon KLINTWORTH
Greenberg dysplasia (ORPHA:1426)
Greenberg dysplasia is a very rare lethal skeletal dysplasia characterized by fetal hydrops, short limbs and abnormal chondro-osseous calcification. The disease is characterized by early in utero lethality and affected fetuses are considered as nonviable.
Epidemiology
Less than ten cases have been published so far.
Clinical description
The main features include fetal hydrops, severe short-limbed dwarfism and a marked disorganization of chondro-osseous calcification. Unusual facial features, cystic hygroma, incomplete lung lobation, pulmonary hypoplasia, extramedullary hematopoiesis, intestinal malrotation and polydactyly may occur.
Etiology
The causative gene has been recently identified as that encoding the lamin B receptor (LBR gene), a member of the sterol reductase family. Mutations in LBR have also been reported to cause Pelger-Huët anomaly (PHA), but in this case transmission occurs in an autosomal dominant manner. PHA is characterized by hypolobulated granulocyte nuclei and abnormal chromatin structure in granulocytes. It has been suggested that homozygous LBR mutations result in distinct mild (PHA homozygosity) or severe (Greenberg skeletal dysplasia) phenotypes based on allelic heterogeneity.
Diagnostic methods
Radiologic abnormalities include a distinctive 'moth-eaten'' appearance of the long bones, marked platyspondyly with multiple abnormal ossification centers, ectopic ossification of the ribs, sternum, pelvis and epiphysis, and deficient ossification of the skull. Histological characterization shows marked disorganization of the cartilaginous architecture, with absence of cartilage column formation, nodular calcifications in cartilage and islands of cartilage surrounded by bone. Greenberg dysplasia has been shown to be associated with an abnormality of cholesterol biosynthesis.
Differential diagnosis
Greenberg dysplasia should be considered in differential diagnosis of cases with severe fetal hydrops (see this term) and phokomelia on antenatal sonography.
Antenatal diagnosis
Prenatal ultrasound diagnosis at 20 weeks of gestation will usually reveal the polyhydramnios, hydrops fetalis, severely short limbs, and cystic hygroma. Sterol profile analysis may be a useful diagnostic tool and can be used for prenatal diagnosis, as can molecular analysis if the mutation in the family is known.
Genetic counseling
It is inherited as an autosomal recessive trait.

                            Last update: 
                            November 2007


                            - Expert reviewer(s): 
                            Pr Raoul HENNEKAM
Greig cephalopolysyndactyly syndrome (ORPHA:380)
A rare developmental defect during embryogenesis with digit duplication, polydactyly, syndactyly, and/or hyperphalangy characterized by multiple congenital anomaly syndrome.
Epidemiology
The precise estimates of birth prevalence are difficult to determine, as ascertainment is erratic (estimated range 1-9/1,000,000).
Clinical description
The primary findings include widely spaced eyes, macrocephaly with frontal bossing, and pre- or post-axial polydactyly and cutaneous syndactyly. The polydactyly is most commonly preaxial in the feet and postaxial in the hands, with variable cutaneous syndactyly, but the limb findings vary significantly. Other low frequency findings include central nervous system (CNS) anomalies, hernias, and cognitive impairment.
Etiology
GCPS is caused by loss of function on chromosome 7p14.1 in the transcription factor gene GLI3.
Diagnostic methods
Clinical diagnosis is challenging because the findings of GCPS are relatively non-specific, and no specific and sensitive clinical criteria have been delineated. A presumptive diagnosis of GCPS can be made if the patient has the classic triad of preaxial polydactyly with cutaneous syndactyly of at least one limb, hypertelorism, and macrocephaly. Individuals with a phenotype consistent with GCPS (but which may not manifest all three attributes listed above) and a GLI3 pathogenic variant may be diagnosed definitively with GCPS. In addition, individuals with a GCPS-consistent phenotype who are related to a definitively diagnosed family member in a pattern consistent with autosomal dominant inheritance may also be diagnosed definitively.
Differential diagnosis
Differential diagnoses include preaxial polydactyly type 4, the GCPS contiguous gene syndrome, acrocallosal syndrome, Gorlin syndrome, Carpenter syndrome, and Teebi syndrome. The disorder is allelic to Pallister-Hall syndrome and one form of the acrocallosal syndrome.
Antenatal diagnosis
Antenatal molecular diagnosis is technically feasible.
Genetic counseling
The disorder is inherited in an autosomal dominant manner. Genetic counseling should be proposed to individuals having the disease-causing mutation informing them that there is 50% risk of passing the pathogenic variant to offspring.
Management and treatment
Treatment of the disorder is symptomatic, with plastic or orthopedic surgery indicated for significant limb malformations.
Prognosis
The prognosis for is generally excellent. There may be a slight increase in the incidence of developmental delay or cognitive impairment. Patients with large deletions that include GLI3 may have a poorer prognosis.

                            Last update: 
                            January 2020


                            - Expert reviewer(s): 
                            Dr Leslie BIESECKER
GRFoma (ORPHA:97261)
GRFoma is a type of pancreatic endocrine tumor (see this term) that hypersecretes growth hormone-releasing factor (GRF or GHRH) and that clinically resembles a pituitary adenoma (see this term) as patients present with acromegaly. In addition to the pancreas, this tumor can also occur in the lungs or small intestine, are usually large > 6cm and approximately 1/3 have metastasized at the time of diagnosis. It often co-occurs with Zollinger-Ellison syndrome or multiple endocrine neoplasia type 1 (MEN 1; see these terms).
GRIN2B-related developmental delay, intellectual disability and autism spectrum disorder (ORPHA:589547)
A rare genetic syndromic intellectual disability characterized by infantile or childhood onset of mild to profound developmental delay and intellectual disability in all affected individuals, as well as variable occurrence of epilepsy, autism spectrum disorder / behavioral issues, microcephaly, muscle tone abnormalities such as hypotonia and spasticity, dystonic, dyskinetic, or choreiform movement disorder, and cortical visual impairment. Brain MRI may reveal abnormal cortical development, hypoplastic corpus callosum, enlarged/dysplastic basal ganglia, and hippocampal dysplasia.
Griscelli syndrome type 2 (ORPHA:79477)
A rare subtype of Griscelli syndrome characterized by pigmentary dilution in skin and hair with irregular clumps of pigment in hair shafts resulting in silvery hair, in association with increased susceptibility to recurrent infections and immunological abnormalities, in particular impairment of T-cell and natural killer cytotoxic activity eventually leading to hemophagocytic lymphohistiocytosis. Patients may present neurological manifestations related to infiltration of the central nervous system in the context of the hemophagocytic syndrome. The disease is mostly fatal in the first decade of life.
Growing teratoma syndrome (ORPHA:314613)
A rare neoplastic disorder characterized by benign metastatic masses increasing in size and number after chemotherapy for non-seminomatous germ cell tumors of testis or ovary. It may present at any time after chemotherapy, with a median occurrence within 24 months after treatment completion. Per definition, the resected specimen exclusively contains mature teratoma components, and serum tumor markers have normalized. The retroperitoneum is the most common site, although almost any other localization has been reported. Increased tumor size may cause mechanical compression of vital organs, with renal dysfunction, bowel ischemia, and biliary obstruction as major complications.
Growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome (ORPHA:391348)
A rare, genetic, mitochondrial oxidative phosphorylation disorder characterized by intrauterine growth retardation, microcephaly, hypotonia, vision impairment, speech and language delay and lactic acidosis with reduced respiratory chain activity (typically complex I). Additonal features may include macrocytic anemia, tremor, muscular atrophy, dysmetria and mild intellectual disability.
Growth delay due to insulin-like growth factor type 1 deficiency (ORPHA:73272)
Growth delay due to insulin-like growth factor I deficiency is characterised by the association of intrauterine and postnatal growth retardation with sensorineural deafness and intellectual deficit.
Epidemiology
The syndrome is extremely rare and only four cases have been reported in the literature so far.
Clinical description
Addition clinical features include microcephaly, adiposity, and insulin resistance. Partial gonadal dysfunction and osteoporosis may also be present. A case of partial IGF-I deficiency has also been described and was associated with pre- and postnatal growth retardation and microcephaly but the developmental delay was mild and hearing tests were normal.
Etiology
IGF-I deficiency is caused by homozygous mutations in the insulin-like growth factor 1 gene (IGFI; 12q22-q24.1). IGF-I is essential for foetal and postnatal growth, brain development and metabolism.
Diagnostic methods
Diagnosis relies on direct sequencing of the five IGF1 exons and of the intron-exon junctions. Measurement of IGF-I levels can be used for diagnosis but the circulating levels of IGF-I vary between patients (ranging from undetectable, low to very high) depending on the molecular defect present and on the immunoassay used.
Differential diagnosis
The differential diagnosis should include growth hormone deficiency and growth hormone resistance (caused by GH receptor or STAT5b anomalies), growth delay due to insulin-like growth factor I resistance and primary acid-labile subunit (ALS) deficiency syndrome (see these terms), as well as secondary IGF-I deficiency due to nutritional problems.
Antenatal diagnosis
Prenatal diagnosis is feasible for families with an identified IGF1 mutation proven to be responsible for the disease phenotype of intrauterine and postnatal growth delay associated with intellectual deficit.
Genetic counseling
IGF-I deficiency is transmitted as an autosomal recessive trait. Affected families should be offered genetic counselling and informed of a 25% risk of recurrence.
Management and treatment
Management involves nutritional and developmental support, together with screening for deafness. Growth velocity in patients with partial IGF-I deficiency can be increased by recombinant growth hormone (GH) therapy. Recombinant IGF-I therapy can be used in patients with complete IGF-I deficiency or those showing an insufficient response to recombinant GH treatment.

                            Last update: 
                            April 2008


                            - Expert reviewer(s): 
                            Pr Yves LE BOUC  - Pr Irène NETCHINE
Growth delay-hydrocephaly-lung hypoplasia syndrome (ORPHA:3035)
Growth delay - hydrocephaly - lung hypoplasia, also named Game-Friedman-Paradice syndrome, is a rare developmental disorder described in 4 sibs so far and characterized by delayed fetal growth, hydrocephaly with patent aqueduct of Sylvius, underdeveloped lungs and various other anomalies such as small jaw, intestinal malrotation, omphalocele, shortness of lower limbs, bowed tibias and foot deformities.
Growth delay-intellectual disability-hepatopathy syndrome (ORPHA:541423)
A rare, genetic, syndromic intellectual disability disease characterized by severe intrauterine and post-natal growth delay, moderate to severe intellectual disability, and neonatal-onset hepatopathy with fibrosis, steatosis, and/or cholestasis, occasionally leading to liver failure. Additional variable manifestations include muscular hypotonia, zinc deficiency, recurrent infections, diabetes mellitus, joint contractures, skin and joint laxity, hypervitaminosis D, and sensorineural hearing loss.
Growth retardation-mild developmental delay-chronic hepatitis syndrome (ORPHA:391366)
Growth retardation-mild developmental delay-chronic hepatitis syndrome is a rare, genetic, parenchymatous liver disease characterized by pre- and postnatal growth retardation, mild global developmental delay, chronic hepatitis with hepatosplenomegaly, Hashimoto thyroiditis, thrombocytopenia, anemia, and B-precursor acute lymphoblastic leukemia.
Grubben-de Cock-Borghgraef syndrome (ORPHA:2101)
Grubben-de Cock-Borghgraef syndrome is a rare intellectual disability syndrome characterized by pre- and postnatal growth deficiency, generalized muscular hypotonia, developmental delay (particularly of speech and language), hypotrophy of distal extremities, small and puffy hands and feet, eczematous skin and dental anomalies (i.e. small, widely-spaced teeth). Partial agenesis of the corpus callosum and a selective immunoglobulin IgG2 subclass deficiency have also been reported in some patients.
GTP cyclohydrolase I deficiency (ORPHA:2102)
GTP-cyclohydrolase I deficiency, an autosomal recessive genetic disorder, is one of the causes of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. Not only does tetrahydrobiopterin deficiency cause hyperphenylalaninemia, it is also responsible for defective neurotransmission of monoamines because of malfunctioning tyrosine and tryptophan hydroxylases, both tetrahydrobiopterin-dependent hydroxylases.
Clinical description
When left untreated, the deficiency causes neurological signs at age 4 or 5 months, although clinical signs are often obvious from birth. The principal symptoms include: psychomotor retardation, tonicity disorders, convulsions, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficulty swallowing.
Diagnostic methods
GTP-cyclohydrolase I deficiency should be suspected in all infants with a positive neonatal screening test for phenylketonuria, especially when hyperphenylalaninemia is moderate. The most effective way to diagnose the disorder is to measure pteridine levels in urine and to confirm the result by measuring neurotransmitters (5-hydroxyindolacetic acid, homovanillic acid) in cerebrospinal fluid and with an oral tetrahydrobiopterin-loading test (20 mg/kg).
Management and treatment
The treatment attempts to bring phenylalaninemia levels back to normal (diet with restricted phenylalanine intake or prescription of tetrahydrobiopterin) and to restore normal monoaminergic neurotransmission by administering precursors (L-dopa/carbidopa and 5-hydroxytryptophane).

                            Last update: 
                            February 2005


                            - Expert reviewer(s): 
                            Pr Jean-Louis DHONDT
Guillain-Barré syndrome (ORPHA:2103)
A clinically heterogeneous spectrum of rare post-infectious neuropathies that usually occur in otherwise healthy patients and encompasses acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN), Miller-Fisher syndrome (MFS) and some other regional variants.
Epidemiology
The overall annual incidence of GBS varies between 1/91,000 and 1/55,000. In Europe and North America, AIDP is the most frequent form of GBS (accounting for around 90% of cases) and thus the term GBS in general is synonymous with AIDP in Western countries. The axonal forms account for only 3-5% of cases in Western countries but are much more frequent (30%-50% of GBS cases) in Asia and Latin America.
Etiology
In the majority of cases, an infectious disease precedes the onset of limb weakness with Campylobacter jejuni infection being the most frequently identified initiating event. GBS has also been reported to occur after vaccination or following a surgical intervention.
Management and treatment
Treatment consists of rapid administration of intravenous immunoglobulin (IVIg) or plasma exchange (PE). Physiotherapy and rehabilitation are also important.
Prognosis
The prognosis is variable depending on the form of GBS and ranges from patients with complete recovery, to those who are unable to walk 6 months after disease onset, and to patients in whom the disease has a fatal outcome.

                            Last update: 
                            December 2009


                            - Expert reviewer(s): 
                            Pr P.A. [Pieter] VAN DOORN
Guttmacher syndrome (ORPHA:2957)
Guttmacher syndrome is an extremely rare syndrome characterized by hypoplastic thumbs and halluces, 5th finger clinobrachydactyly, postaxial polydactyly of the hands, short or uniphalangeal 2nd toes with absent nails and hypospadias.
Epidemiology
It has been described in a father and his son and daughter.
Clinical description
The affected patients have normal mental development. Except for postaxial polydactyly of the hands and uniphalangeal 2nd toes with absent nails, features are in common with hand-foot-genital syndrome (HFGS, see this term) caused by mutations in the HOXA13 gene.
Etiology
In all three affected individuals with Guttmacher syndrome, two different sequence alterations were identified in HOXA13 gene: a de novo missense mutation and a deletion in the promoter region of the gene, inherited from an unaffected parent, which may contribute to the phenotype in the affected individuals.
Genetic counseling
The condition is inherited in an autosomal dominant manner.

                            Last update: 
                            January 2011
Gómez-López-Hernández syndrome (ORPHA:1532)
A rare neurocutaneous syndrome characterized by the association of cerebellum (rhombencephalosynapsis), cranial nerves (trigeminal anesthesia), and scalp (alopecia) abnormalities. Other features observed in patients were craniosynostosis, midfacial hypoplasia, bilateral corneal opacities, low-set ears, short stature, moderate intellectual impairment and ataxia. Hyperactivity, depression, self-injurious behaviour and bipolar disorder have also been reported.
Haddad syndrome (ORPHA:99803)
Haddad syndrome is a rare congenital disorder in which congenital central hypoventilation syndrome (CCHS), or Ondine syndrome, occurs concurrently with Hirschsprung disease (see these terms).
Epidemiology
Birth incidence of Ondine syndrome is 1 in 200,000 live-births and Hirschsprung disease occurs concurrently in 16% of cases.
Clinical description
Intestinal aganglionosis is more extensive, and the gender ratio is 1:1, unlike in classical Hirschsprung disease.
Etiology
Mutations in the PHOX2B gene are found in a significant number of patients with Haddad syndrome.

                            Last update: 
                            November 2010