TaoMedAI/RareMedData huggingface dataset:
Congenital factor XIII deficiency (ORPHA:331)
Congenital factor XIII deficiency is an inherited bleeding disorder due to reduced levels and activity of factor XIII (FXIII) and characterized by hemorrhagic diathesis frequently associated with spontaneous abortions and defective wound healing. Factor XIII deficiency is one of the most rare coagulation factor deficiencies.
Epidemiology
Prevalence of homozygous forms is estimated at around 1/2,000,000. Both sexes are equally affected.
Clinical description
Congenital FXIII deficiency can manifest at any age, but diagnosis is often made during infancy. Umbilical stump bleeding manifests in up to 80% of patients. Other common signs include intracranial hemorrhage (25-30%), soft tissue bleeding, bruising, hemarthroses (20%), and recurrent spontaneous abortions. In most cases, hemorrhages are delayed (12-36hr) after trauma or surgery. Patients may have poor wound healing. Acquired forms of the disease have also been reported in association with hepatic failure, inflammatory bowel disease (see this term), and myeloid leukemia.
Etiology
Congenital FXIII deficiency is usually caused by mutations in the F13A1 gene (6p24.2-p23) encoding the catalytic A subunit, but mutations have also been found in the F13B gene (1q31-q32.1) encoding the B subunit. Transmission is autosomal recessive. The phenotype is less severe when the F13B gene is mutated.
Diagnostic methods
Diagnosis is based on quantitative FXIII activity measurement and antigen assays. Common clotting assays such as activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) are normal and cannot be used for the screening. The clot solubility test may also be used (clot is stable for more than 24 hours in case of FXIII deficiency). Molecular testing is available, but unnecessary for diagnosis.
Differential diagnosis
Differential diagnoses mainly include the other congenital coagulation factor deficiencies: fibrinogen, factors II, V, VII, X, XI, VIII, IX (see these terms).
Antenatal diagnosis
Antenatal diagnosis is possible if the causal mutations have previously been identified in the family.
Management and treatment
Factor XIII concentrates or fresh frozen plasma (when FXIII concentrates are not available) is usually used for the treatment of bleedings. Prophylactic therapy with FXIII concentrate should be indicated to prevent recurrent bleedings such as intracranial hemorrhage.
Prognosis
Intracranial hemorrhage can be life threatening, but prognosis is favorable if adequate treatment is provided.

                            Last update: 
                            October 2009


                            - Expert reviewer(s): 
                            Pr Jenny GOUDEMAND
Congenital fibrinogen deficiency (ORPHA:335)
Rare inherited coagulation disorders characterized by bleeding symptoms ranging from mild to severe resulting from reduced quantity and/or quality of circulating fibrinogen. Afibrinogenemia (complete absence of fibrinogen) and hypofibrinogenemia (reduced plasma fibrinogen concentration) correspond to quantitative anomalies of fibrinogen while dysfibrinogenemia corresponds to a functional anomaly of fibrinogen. Hypo- and dysfibrinogenemia may be frequently combined (hypodysfibrinogenemia).
Epidemiology
Prevalence of afibrinogenemia is estimated at 1/1,000,000. Hypo- and dysfibrinogenemia are more frequent. Both sexes are equally affected. Fibrinogen deficiency can be discovered at any age but afibrinogenemia usually manifests early in childhood, often in the neonatal period.
Clinical description
Common manifestations of afibrinogenemia include umbilical cord bleeding, epistaxis, hemarthrosis, gastrointestinal bleeding, menorrhagia, traumatic and surgical bleeding and, rarely, intracranial hemorrhage. Recurrent spontaneous abortions may occur in women affected with afibrinogenemia. Hypofibrinogenemia is characterized by fewer and milder bleeding episodes following trauma or surgery. Most of patients with dysfibrinogenemia are asymptomatic (60%). The others may have bleeding symptoms (28%) or even thrombosis (20%).
Etiology
Congenital deficiencies of fibrinogen are caused by mutations in the FGA, FGB, or FGG genes. Afibrinogenemia is autosomal recessive; hypofibrinogenemia and dysfibrinogenemia are mainly autosomal dominant.
Diagnostic methods
Diagnosis is based on prolonged activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin and reptilase times and on fibrinogen levels measured by functional (Clauss) and immunological assays.
Differential diagnosis
Differential diagnoses include the other congenital clotting factor deficiencies (Factors II, V, VII, X, XI, VIII, IX and XIII; see these terms) and acquired fibrinogen deficiency (consumptive coagulopathy, hepatic failure). In case of thrombosis, differential diagnosis also includes congenital or acquired thrombophilia (antithrombin deficiency, protein C or S deficiency, Factor V Leiden mutation, lupus anticoagulant (see these terms) and FII Leiden mutation).
Antenatal diagnosis
Antenatal diagnosis of afibrinogenemia is possible if the causal mutations have already been identified in the family.
Management and treatment
Fibrinogen concentrates are usually used for the treatment of hemorrhages. Fresh frozen plasma is used when fibrinogen concentrates are not available. Recurrent spontaneous abortions can be prevented by routine prophylaxis based on administration of fibrinogen concentrates early in pregnancy.
Prognosis
Although life-threatening intracranial hemorrhage may occur, prognosis of afibrinogenemia is good with early diagnosis and adequate treatment. Prognosis of hypo- or dysfibrinogenemia is usually good.

                            Last update: 
                            October 2009


                            - Expert reviewer(s): 
                            Pr Jenny GOUDEMAND
Congenital fibrosis of extraocular muscles (ORPHA:45358)
A rare syndromic disorder with strabismus characterized by congenital non-progressive ophthalmoplegia affecting the oculomotor and/or trochlear nucleus/nerve and their innervated muscles. Patients present with abnormal resting position of the eyes (in most cases infraducted and exotropic), limitation of vertical and horizontal gaze, impaired binocular vision, amblyopia, unilateral or bilateral blepharoptosis, and compensatory abnormal head posture. Extraocular manifestations include intellectual disability, peripheral neuropathy, and skeletal abnormalities, among others.
Congenital generalized hypercontractile muscle stiffness syndrome (ORPHA:476406)
A rare defect of tropomyosin characterized by decreased fetal movements and generalized muscle stiffness at birth. Additional features include joint contractures, short stature, kyphosis, dysmorphic features, temperature dysregulation, and variably severe respiratory involvement with hypoxemia. Muscle biopsy shows mild myopathic features.
Congenital generalized hypertrichosis, Ambras type (ORPHA:1023)
Congenital generalized hypertrichosis, Ambras type is an extremely rare type of hypertrichosis lanuginosa congenita, a congenital skin disease, that is characterized by the presence of vellus-type hair on the entire body, especially on the face, ears and shoulders, with the exception of palms, soles, and mucous membranes. Facial and dental anomalies can also be observed, such as triangular, coarse face, bulbous nasal tip, long palpebral fissures, delayed tooth eruption and absence of teeth.
Congenital genu flexum (ORPHA:295232)
A rare congenital knee dislocation characterized by permanent knee flexion with limited extension. It can be unilateral or bilateral and may occur as an isolated malformation or be part of a syndrome (especially arthrogryposis multiplex congenita).
Congenital genu recurvatum (ORPHA:295229)
A rare congenital knee dislocation characterized by hyperextension of the knee greater than 0° associated with limited flexion, with prominence of the femoral condyles in the popliteal fossa and increased transverse skin folds over the anterior surface of the knee. It can be unilateral or bilateral and may occur as an isolated malformation, be associated with other orthopedic abnormalities (like developmental dysplasia of the hip or clubfoot) or be part of a syndrome (e. g. Larsen's syndrome).
Congenital Gerbode defect (ORPHA:99095)
A rare, congenital non-syndromic heart malformation characterized by an abnormal shunting between the left ventricle and right atrium. The clinical manifestation varies, depending on the volume of the shunt. Small congenital shunts are usually asymptomatic or associated with dyspnea and fever, whereas larger shunts often present with chest pain, fatigue, weakness, lower extremity edema, and sometimes heart failure and death. Other congenital heart anomalies may be associated.
Congenital glucokinase-related hyperinsulinism (ORPHA:79299)
A form of diffuse hyperinsulinism due to glucokinase hyperactivity and characterized by an excessive/ uncontrolled insulin secretion (inappropriate for the level of glycemia) and recurrent episodes of hypoglycemia induced by fasting and glucose rich meals. The clinical spectrum can range from mild and intermediate cases that respond well to dietary modifications and medical management with diazoxide to severe cases that are unresponsive to diazoxide. The potential development of type 2 diabetes with age is another notable feature.
Congenital heart block (ORPHA:60041)
Congenital heart block (CHB) is a rare disorder of atrioventricular conduction, characterized by absence of conduction of atrial impulses to the ventricles with slower ventricular rhythm (atrioventricular dissociation). CHB can occur in association with immunological evidence of maternal connective disease (autoimmune CHD), fetal structural CHD or can be idiopathic.
Congenital heart defect-round face-developmental delay syndrome (ORPHA:1355)
A very rare syndrome described in three sibs of one Japanese family and characterized by congenital heart disease, round face with depressed nasal bridge, small mouth, short stature, and relatively dark skin and typical dermatoglyphic anomalies, and intellectual deficit.
Congenital hereditary endothelial dystrophy type II (ORPHA:293603)
Congenital hereditary endothelial dystrophy II (CHED II) is a rare subtype of posterior corneal dystrophy (see this term) characterized by a diffuse ground-glass appearance of the corneas and marked corneal thickening from birth with nystagmus, and blurred vision.
Epidemiology
Prevalence of this form of corneal dystrophy is unknown. Most cases have been identified in children of consanguineous parents from Saudi Arabia, India, Pakistan, Myanmar (Burma) and Ireland.
Clinical description
Diffuse ground glass lesions are present from birth and are accompanied by nystagmus. Tearing and photophobia are minimal or absent. The course is relatively stable. Patients also occasionally have sensorineural deafness. The cornea is swollen due to extensive stromal edema.
Etiology
Most cases are caused by homozygous mutations in the SLC4A11 gene. A high degree of mutational heterogeneity has been detected and genetic heterogeneity may exist as no mutations in SLC4A11 or in its promoter region have been detected in some affected families. In CHED II, an increased tendency for the abnormal endothelium to synthesize a homogenous, posterior, non-banded Descemet membrane is observed.
Genetic counseling
Transmission appears to be autosomal recessive.
Management and treatment
Patients with CHED II usually require a penetrating keratoplasty. Procedures for repairing the posterior surface of the cornea, such as a deep lamellar endothelial keratoplasty (DLEK), Descemet stripping endothelial keratoplasty (DSEK), or Descemet stripping automated endothelial keratoplasty (DSAEK) are technically difficult in young children.

                            Last update: 
                            May 2012


                            - Expert reviewer(s): 
                            Dr Gordon KLINTWORTH
Congenital hereditary facial paralysis-variable hearing loss syndrome (ORPHA:306530)
Congenital hereditary facial paralysis-variable hearing loss syndrome is an extremely rare autosomal recessive disorder characterized by bilateral facial palsy with masked facies, sensorineural hearing loss, dysmorphic features (midfacial retrusion, low-set ears), and strabismus.
Congenital herpes simplex virus infection (ORPHA:293)
Congenital herpes virus infection is a group of anomalies that an infant may present as a result of maternal infection and subsequent foetal infection with herpes virus. This virus causes recurrent cutaneous infections in adults, often involving the lips or the genitalia. Herpes infections in other organs, such as the liver or central nervous system, are less frequent.
Clinical description
Skin lesions and scars, chorioretinitis, microcephaly, hydrencephaly, and microphthalmia have been described in infants with in utero primary herpes virus infections, but a causal relationship between these manifestations and the infection could not be established. Pregnancy complications including preterm delivery, intrauterine growth retardation, and neonatal infection have been attributed to the herpes virus.
Etiology
There are two types of virus (HSV-1 and HSV-2) and both appear to have the same activity. However, type 1 infections more commonly involve the oral cavity, whereas type 2 infections more commonly involve the genital region. It has been suggested that latent HSV-2 infections occur in as many as 20 to 40% of women. Exposure of the foetus to herpes virus at the time of delivery carries a serious risk of infection for the newborn. This risk may be high during the initial infection of the mother (33 to 50%), but probably does not exceed 3% in cases of reinfection because of the protective effect of maternal antibodies.
Differential diagnosis
It remains difficult to distinguish between cases with a primary infection and those with a previously undetected recurrent infection that has become symptomatic during pregnancy.
Management and treatment
In spite of described cases of serious foetal illness, primary infection with herpes virus during pregnancy is not an indication for therapeutic abortion, and the use of antivirals in the treatment of primary herpes infections during gestation has been recommended. Some authors recommend caesarean delivery for women with first-episode genital herpes lesions at the time of delivery.

                            Last update: 
                            March 2006


                            - Expert reviewer(s): 
                            Dr Elisabeth ROBERT-GNANSIA
Congenital high-molecular-weight kininogen deficiency (ORPHA:483)
A rare genetic hematologic disease characterized by abnormal surface-mediated activation of fibrinolysis due to the deficiency of high-molecular-weight kininogen in plasma. Activated partial thromboplastin time (aPTT) may be prolonged. Clinically, patients are typically asymptomatic and do not show increased bleeding or thrombotic tendency.
Congenital Horner syndrome (ORPHA:91413)
Congenital Horner syndrome is a rare neurological disorder characterized by relative pupillary miosis and blepharoptosis, evident at birth, caused by interruption of the oculosympathetic innervation at any point along the neural pathway from the hypothalamus to the orbit. Often additional symptoms, such as enophthalmos, facial anhidrosis, iris heterochromia, conjunctival congestion, transient hypotonia and/or pupillary dilation lag, may be present. Association with birth trauma, neoplasms or vascular malformations has been reported.
Congenital hydrocephalus (ORPHA:2185)
A rare central nervous system malformation characterized by abnormally enlarged cerebral ventricles due to impaired cerebrospinal fluid circulation. It arises in utero and can be either acquired or inherited. The severity of the resulting brain damage depends on the duration and extent of ventriculomegaly.
Congenital hyperinsulinism due to HNF4A deficiency (ORPHA:263455)
A form of diazoxide-sensitive diffuse congenital hyperinsulinism due to HNF4A deficiency and, characterized by macrosomia, transient or persistent hyperinsulinemic hypoglycemia (HH), responsiveness to diazoxide and a propensity to develop maturity-onset diabetes of the young subtype 1 (MODY).
Congenital hypothyroidism due to maternal intake of antithyroid drugs (ORPHA:226313)
A rare congenital hypothyroidism disorder characterized by transient, primary, fetal or neonatal hypothyroidism resulting from transplacental transfer of antithyroid drugs due to maternal intake. Patients may present fetal or neonatal goiter, hoarse cry, reduced tendon reflexes, feeding difficulty, constipation, prolonged jaundice and/or respiratory distress. Elevated levels of T4 and thyroid stimulating hormone usually normalize without treatment within 3 weeks of birth.
Congenital hypothyroidism due to transplacental passage of TSH-binding inhibitory antibodies (ORPHA:95715)
Congenital hypothyroidism due to transplacental passage of maternal thyroid-stimulating hormone (TSH)-binding inhibitory antibodies is a type of transient congenital hypothyroidism (see this term), a thyroid hormone deficiency that is not permanent.
Epidemiology
Prevalence is estimated to be 1/100,000.
Clinical description
Patients may present with symptoms similar to those of permanent CH (see this term) or they may be asymptomatic.
Etiology
It is caused by the transfer of maternal TSH blocking antibodies, which can block the TSH receptor in the neonatal thyroid resulting in hypothyroidism in the infant. The effect can last up to 3-6 months after birth as maternal antibody levels fall.
Management and treatment
Treatment with l-thyroxine is usually required during this period.

                            Last update: 
                            August 2010


                            - Expert reviewer(s): 
                            Dr Stephen LAFRANCHI  - Dr Maynika RASTOGI
Congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome (ORPHA:352333)
A rare autosomal ichthyosis syndrome with prominent neurologic signs characterized by the association of congenital ichthyosis with global developmental delay, intellectual disability, infantile-onset seizures, and spastic tetraplegia. Brain imaging may show delayed myelination and cerebral atrophy. Marked intrafamilial variability has been reported.
Congenital ichthyosis-microcephalus-tetraplegia syndrome (ORPHA:2271)
A rare autosomal ichthyosis syndrome with prominent neurologic signs characterized by the association of congenital ichthyosis with severe developmental delay, microcephaly, spastic tetraplegia, sensorineural hearing impairment, athetosis, and myoclonus. Marked epileptic discharges with occurrence of tonic spasms have also been reported. Cerebral MRI shows diffuse cortical atrophy. There have been no further descriptions in the literature since 1995.
Congenital infiltrating lipomatosis of the face (ORPHA:583097)
A rare PIK3CA-related overgrowth syndrome characterized by congenital non-hereditary facial overgrowth due to post-zygotic activating mutations in the PIK3CA gene. It is unilateral and involves hypertrophy of both the soft and hard tissue structures on the affected side of the face, including hypertrophy of the facial bones, macroglossia, and proliferation of the parotid gland. Early eruption of the teeth is common.
Congenital insensitivity to pain with severe intellectual disability (ORPHA:453510)
Congenital insensitivity to pain with severe intellectual disability is a rare autosomal recessive hereditary sensory and autonomic neuropathy characterized by the complete absence of pain perception from birth, an unresponsiveness to soft touch, severe non-progressive cognitive delay, and normal motor movement/behavior and strength. Affected cases retained hot and cold perception.
Congenital insensitivity to pain-anosmia-neuropathic arthropathy (ORPHA:88642)
A rare genetic peripheral neuropathy characterized by complete congenital insensitivity to painful stimuli, commonly associated with neuropathic arthropathy. In addition, patients are typically anosmic.
Congenital insensitivity to pain-hyperhidrosis-absence of cutaneous sensory innervation (ORPHA:217399)
A rare hereditary sensory and autonomic neuropathy characterized by congenital insensitivity to pain, general hypesthesia, diminished temperature sensitivity, and hyperhidrosis. Motor function is preserved. Skin biopsy reveals lack of cutaneous innervation except for sensory and autonomic innervation of blood vessels and sweat glands.
Congenital intrauterine infection-like syndrome (ORPHA:1229)
Congenital intrauterine infection-like syndrome is characterised by the presence of microcephaly and intracranial calcifications at birth accompanied by neurological delay, seizures and a clinical course similar to that seen in patients after intrauterine infection with Toxoplasma gondii, Rubella, Cytomegalovirus, Herpes simplex (so-called TORCH syndrome), or other agents, despite repeated tests revealing the absence of any known infectious agent.
Epidemiology
More than 30 cases have been described in the literature so far.
Clinical description
The clinical presentation of the reported cases is rather heterogeneous with variable manifestations including intrauterine growth retardation, hepatosplenomegaly, hyperbilirubinaemia, cerebellar hypoplasia or atrophy, and congenital cataract. Affected individuals with associated thrombocytopaenia have also been reported but it has been suggested that these patients may have a distinct subtype.
Etiology
The cause remains unknown.
Diagnostic methods
Diagnosis relies on the clinical picture and requires exclusion of intrauterine infections.
Differential diagnosis
Congenital intrauterine infection-like syndrome shows considerable clinical overlap with Aicardi-Goutieres syndrome (AGS, see this term). The two syndromes were reported to differ by the presence of cerebrospinal fluid anomalies (CSF leucocytosis and elevated IFN-alpha levels) in AGS and hepatic dysfunction, congenital microcephaly and thrombocytopaenia in congenital intrauterine infection-like syndrome. However, as the clinical manifestations of both syndromes show significant variability, it has been suggested that AGS and congenital intrauterine infection-like syndrome represent different presentations of the same disease. The differential diagnosis should also include other syndromes characterised by microcephaly and intracranial calcification such as Cockayne syndrome, COFS syndrome (which is usely considered as the neonatal form of Cockayne syndrome) and Hoyeraal-Hreidarsson syndrome (the neonatal presentation of dyskeratosis congenita syndrome; see these terms), some cases of mitochondrial encephalomyopathy, and pseudohypoarathyroidism. Ancient cases may have been reported as ``Fahr disease'', an outdated, causally heterogeneous clinical entity that encompasses several entities with intracranial calcifications.
Genetic counseling
Several familial cases, compatible with an autosomal recessive pattern of inheritance, have been described.
Management and treatment
Treatment is symptomatic only.
Prognosis
The prognosis is variable but can be severe with several of the reported patients dying within the first year of life.

                            Last update: 
                            May 2008


                            - Expert reviewer(s): 
                            Pr Alain VERLOES