Treatment of asymptomatic congenital dysfibrinogenemia depends in part on the expectations of developing bleeding and/or thrombotic complications as estimated based on the history of family members with the disorder and, where available, determination of the exact mutation causing the disorder plus the propensity of the particular mutation type to develop these complications. In general, individuals with this disorder require regular follow-up and multidiscipline management prior to surgery, pregnancy, and giving childbirth. Women with the disorder appear to have an increased rate of miscarriages and all individuals with fibrinogen activity in clotting tests below 0.5 grams/liter are prone to bleeding and spontaneous abortions. Women with multiple miscarriages and individuals with excessively low fibrinogen activity levels should be considered for prophylaxis therapy with fibrinogen replacement during pregnancy, delivery, and/or surgery.

Diagnosis of acquired dysfibrinogenemia uses the same laboratory tests that are used for congenital dysfibrinogenemia plus evidence for an underlying causative disease.

Hypodysfibrinogenemia is usually diagnosed in individuals who: have a history of abnormal bleeding or thrombosis or are a close blood relative of such an individual. Initial laboratory findings include a decrease in serum fibrinogen mass levels as measured by immunoassay plus a reduction in inducible blood clot formation so that the ratio of functionally-detected fibrinogen mass (i.e. detected in induced clots) to immunoassay-detected fibrinogen mass is abnormally low, i.e. <0.7. This contrast with individuals with congenital dysfibrinogenemia who exhibit normal levels of fibrinogen as measured by immunoassay but low functionally-detected to immunoassay-detected fibrinogen mass ratios, i.e. <0.7. Where available, specialized laboratories can conduct studies to define the exact gene mutation(s) and fibrinogen abnormalities underlying the disorder.

Blood relatives of the proband case should be evaluated for the presence of hypodysfibrinogenemia. Individuals with the disorder need to be advised on its inheritance, complications, and preventative measures that can be taken to avoid bleeding and/or thrombosis. Since >80% of individuals may develop bleeding or thrombosis complications of the disorder, asymptomatic individuals diagnosed with hydposyfibrinogenemia are best handled at a specialized center in order to benefit from multidisciplinary management.

Measures to prevent and/or treat complications of hypodysfibrinogenemia should be tailored to the personal and family history of the individual by a specialized center. Individuals with a personal or family history of bleeding are considered to be of low risk of bleeding when their functional fibrinogen levels are >1 gram/liter for major surgery, >0.5 gram/liter for minor surgery, >0.5 to 1-2 gram/liter for spontaneous bleeding (depending on its severity), >0.5 to > 1 gram/liter for the first two trimesters of pregnancy, and >1 to <2 gram/liter for the last trimester of pregnancy and postpartum period. Functional fibrinogen below these levels should be treated preferably with fibrinogen concentrate or if not available, fibrinogen-rich cryoprecipitate or plasma to attain low risk levels of functional fibrinogen. Antifibrinolytic drugs such as tranexamic acid or (ε-aminocaproic acid) may be considered as an alternative preventative or therapeutic treatments in cases of minor surgery, dental extractions, mucosal bleeding, or other episodes of mild bleeding. In individuals with a personal or family history of thrombosis, should be considered for long-term anticoagulation drugs such as low molecular weight heparin, coumadin, or rivaroxaban.

There are divergent views as to whether everyone with an unprovoked episode of thrombosis should be investigated for thrombophilia. Even those with a form of thrombophilia may not necessarily be at risk of further thrombosis, while recurrent thrombosis is more likely in those who have had previous thrombosis even in those who have no detectable thrombophilic abnormalities. Recurrent thromboembolism, or thrombosis in unusual sites (e.g. the hepatic vein in Budd-Chiari syndrome), is a generally accepted indication for screening. It is more likely to be cost-effective in people with a strong personal or family history of thrombosis. In contrast, the combination of thrombophilia with other risk factors may provide an indication for preventative treatment, which is why thrombophilia testing may be performed even in those who would not meet the strict criteria for these tests. Searching for a coagulation abnormality is not normally undertaken in patients in whom thrombosis has an obvious trigger. For example, if the thrombosis is due to immobilization after recent orthopedic surgery, it is regarded as "provoked" by the immobilization and the surgery and it is less likely that investigations will yield clinically important results.

When venous thromboembolism occurs when a patient is experiencing transient major risk factors such as prolonged immobility, surgery, or trauma, testing for thrombophilia is not appropriate because the outcome of the test would not change a patient's indicated treatment. In 2013, the American Society of Hematology, as part of recommendations in the Choosing Wisely campaign, cautioned against overuse of thrombophilia screening; false positive results of testing would lead to people inappropriately being labeled as having thrombophilia, and being treated with anticoagulants without clinical need

In the United Kingdom, professional guidelines give specific indications for thrombophilia testing. It is recommended that testing be done only after appropriate counseling, and hence the investigations are usually not performed at the time when thrombosis is diagnosed but at a later time. In particular situations, such as retinal vein thrombosis, testing is discouraged altogether because thrombophilia is not regarded as a major risk factor. In other rare conditions generally linked with hypercoagulability, such as cerebral venous thrombosis and portal vein thrombosis, there is insufficient data to state for certain whether thrombophilia screening is helpful, and decisions on thrombophilia screening in these conditions are therefore not regarded as evidence-based. If cost-effectiveness (quality-adjusted life years in return for expenditure) is taken as a guide, it is generally unclear whether thrombophilia investigations justify the often high cost, unless the testing is restricted to selected situations.

Recurrent miscarriage is an indication for thrombophilia screening, particularly antiphospholipid antibodies (anti-cardiolipin IgG and IgM, as well as lupus anticoagulant), factor V Leiden and prothrombin mutation, activated protein C resistance and a general assessment of coagulation through an investigation known as thromboelastography.

Women who are planning to use oral contraceptives do not benefit from routine screening for thrombophilias, as the absolute risk of thrombotic events is low. If either the woman or a first-degree relative has suffered from thrombosis, the risk of developing thrombosis is increased. Screening this selected group may be beneficial, but even when negative may still indicate residual risk. Professional guidelines therefore suggest that alternative forms of contraception be used rather than relying on screening.

Thrombophilia screening in people with arterial thrombosis is generally regarded unrewarding and is generally discouraged, except possibly for unusually young patients (especially when precipitated by smoking or use of estrogen-containing hormonal contraceptives) and those in whom revascularization, such as coronary arterial bypass, fails because of rapid occlusion of the graft.

Tests for thrombophilia include complete blood count (with examination of the blood film), prothrombin time, partial thromboplastin time, thrombodynamics test, thrombin time and reptilase time, lupus anticoagulant, anti-cardiolipin antibody, anti-β2 glycoprotein 1 antibody, activated protein C resistance, fibrinogen tests, factor V Leiden and prothrombin mutation, and basal homocysteine levels. Testing may be more or less extensive depending on clinical judgement and abnormalities detected on initial evaluation.

For hereditary cases, the patient must have at least 2 abnormal tests plus family history.

Suggested diagnostic criteria for cryoglobulinemic disease fall into the following obligatory and additional categories:

- Obligatory criteria: 1) cold sensitivity; 2) cutaneous symptoms (i.e. urticaria, purpura, Raynaud phenomenon, ulceration/necrosis/gangrene, and/or livedo reticularis); 3) arterial and/or venous thrombotic events; fever; 4) arthralgia/myalgia; 5) neuritis in >1 site; and 6) renal disorder.

- Additional criteria: 1) typical biopsy findings at site(s) of involvement and 2) angiogram evidence of occlusion in one or more small to medium sized arteries.

The diagnosis of secondary cryofibrinogenemia also requires evidence for the cited infectious, malignant, premalignant vasculitis, and autoimmune disorders while the diagnosis of primary cryofibriongenemia requires a lack of evidence for 1) the cited associated disorders, 2) other vascular occlusive diseases, and 3) cryoglobulinemia.

Fibrinogen disorders are set of hereditary or acquired abnormalities in the quantity and/or quality of circulating fibrinogens. The disorders may lead to pathological bleeding and/or blood clotting or the deposition of fibrinogen in the liver, kidneys, or other organs and tissues. These disorders include:

- Congenital afibrinogenemia, an inherited blood disorder in which blood does not clot normally due to the lack of fibrinogen; the disorder causes abnormal bleeding and thrombosis.

- Congenital hypofibrinogenemia, an inherited disorder in which blood may not clot normally due to reduced levels of fibrinogen; the disorder may cause abnormal bleeding and thrombosis.

- Fibringogen storage disease, a form of congenital hypofibrinogenemia in which specific hereditary mutations in fibrinogen cause it to accumulate in, and damage, liver cells. The disorder may lead to abnormal bleeding and thrombosis but also to cirrhosis.

- Congenital dysfibrinogenemia, an inherited disorder in which normal levels of fibrinogen composed at least in part of a dysfunctional fibrinogen may cause abnormal bleeding and thrombosis.

- Hereditary fibrinogen Aα-Chain amyloidosis, a form of dysfibrinogenemia in which certain fibrinogen mutations cause blood fibrinogen to accumulate in the kidney and cause one type of familial renal amyloidosis; the disorder is not associated with abnormal bleeding or thrombosis.

- Acquired dysfibrinogenemia, a disorder in which normal levels of fibrinogen are composed at least in part of a dysfunctional fibrinogen due to an acquired disorder (e.g. liver disease) that leads to the synthesis of an incorrectly glycosylated (i.e. wrong amount of sugar residues) added to an otherwise normal fibrinogen. The incorrectly glycosalated fibrinogen is dysfunctional and may cause pathological episodes of bleeding and/or blood clotting.

- Congenital hypodysfibrinogenemia, an inherited disorder in which low levels of fibrinogen composed at least in part of a dysfunctional fibrinogen may cause pathological episodes of bleeding or blood clotting.

- Cryofibrinogenemia, an acquired disorder in which fibrinogen precipitates at cold temperatures and may lead to the intravascular precipitation of fibrinogen, fibrin, and other circulating proteins thereby causing the infarction of various tissues and bodily extremities.

Studies on the treatment of cryofibrinoginemic disease have involved relatively few patients, are limited primarily to case reports, and differ based on whether the disease is primary or secondary. In all cases of cryofibrinogenemic disease, however, patients should avoid the exposure of afflicted body parts to cold weather or other environmental triggers of symptoms and avoid using cigarettes or other tobacco products. In severe cases, these individuals also risk developing serious thrombotic events which lead to tissue necrosis that may result in secondary bacterial infections and require intensive antimicrobial therapy and/or amputations. Careful treatment of these developments is required.

An absolute neutrophil count (ANC) chronically less than 500/mm3, usually less than 200/mm3, is the main sign of Kostmann's. Other elements include the severity of neutropenia, the chronology (from birth; not emerging later), and other normal findings (hemoglobin, platelets, general body health). Isolated neutropenia in infants can occur in viral infections, autoimmune neutropenia of infancy, bone marrow suppression from a drug or toxin, hypersplenism, and passive placental transfer of maternal IgG.

A bone marrow test can assist in diagnosis. The bone marrow usually shows early granulocyte precursors, but myelopoietic development stops ("arrests") at the promyelocyte and/or myelocyte stage, so that few maturing forms are seen. Neutrophil survival is normal.

Needs mention of (rarer) myelokathexis types. e.g. G6PC3 variant and

All patients with symptomatic cryoglobulinemia are advised to avoid, or protect their extremities, from exposure to cold temperatures. Refrigerators, freezers, and air-conditioning represent dangers of such exposure.

Cryoglobulinemia and cryoglobulinemic disease must be distinguished from cryofibrinogenemia or cryofibrinogenemic disease, conditions which involve the cold-induced intravascular deposition of circulating native fibrinogens. The cryoglobulins in plasma or serum precipitate at lower temperatures (e.g. 4°C). Since cryofibrinogens are present in plasma but greatly depleted in serum, precipitation tests for them are positive in plasma but negative in serum. Cryofibrinogenemia is occasionally found in cases of cryoglobulinemic disease. Cryoglobulinemic disease must also be distinguished from frostbite as well as numerous other conditions that have a clinical (particularly cutaneous) presentation similar to cryoglobulinemic disease but are not exacerbated by cold temperature, e.g. dysfibrinogenemia and dysfibrinogenemic disease (conditions involving the intravascular deposition of genetically abnormal circulating fibrinogens), purpura fulminans, cholesterol emboli, warfarin necrosis, ecthyma gangrenosum, and various hypercoagulable states.

Rheumatoid factor is a sensitive test for cryoglobulinemia. The precipitated cryoglobulins are examined by immunoelectrophoresis and immunofixation to detect and quantify the presence of monoclonal IgG, IgM, IgA, κ light chain, or λ light chain immunoglobins. Other routine tests include measuring blood levels of rheumatoid factor activity, complement C4, other complement components, and hepatitic C antigen. Biopsies of skin lesions and, where indicated, kidney or other tissues can help in determining the nature of the vascular disease (immunoglobulin deposition, cryoglobulinemic vasculitis, or, in cases showing the presence of cryfibrinogenemia, fibrinogen deposition. In all events, further studies to determine the presence of hematological, infections, and autoimmune disorders are conducted on the basis of these findings as well as each cases clinical findings.

Regular administration of exogenous granulocyte colony-stimulating factor (filgrastim) clinically improves neutrophil counts and immune function and is the mainstay of therapy, although this may increase risk for myelofibrosis and acute myeloid leukemia in the long term.

Over 90% of SCN responds to treatment with granulocyte colony-stimulating factor (filgrastim), which has significantly improved survival.

Familial renal amyloidosis (or familial visceral amyloidosis, or hereditary amyloid nephropathy) is a form of amyloidosis primarily presenting in the kidney.

It is associated most commonly with congenital mutations in the fibrinogen alpha chain and classified as a dysfibrinogenemia (see Hereditary Fibrinogen Aα-Chain Amyloidosis). and, less commonly, with congenital mutations in apolipoprotein A1 and lysozyme.

It is also known as "Ostertag" type, after B. Ostertag, who characterized it in 1932 and 1950.

The condition is usually congenital, but sporadic cases have also been reported. It may be associated with other congenital defects, commonly with autosomal recessive polycystic kidney disease, the most severe form of PKD. Some suggest that these two conditions are one disorder with different presentation.

Congenital hepatic fibrosis is an inherited fibrocystic liver disease associated with proliferation of interlobular bile ducts within the portal areas and fibrosis that do not alter hepatic lobular architecture. The fibrosis would affect resistance in portal veins leading to portal hypertension.

If a patient displays congenital melanocytic nevi or giant congenital melanocytic nevi, the criteria for diagnosis of neurocutaneous melanosis is as follows:

- Melanocytic deposits exist within the central nervous system that are either malignant or benign

- The cutaneous lesions, giant or otherwise, are not malignant

This criteria is typically validated through biopsy of the cutaneous lesions and imaging of the central nervous system. It is important to establish that the cutaneous lesions are benign. If not, then the melanocytic deposits in the central nervous system may be the result of metastasis of cutaneous melanoma and not neurocutaneous melanosis.

Imaging has been shown to be the only reliable detection method for the presence of neurocutaneous melanosis that can be performed in living patients. Currently, the preferred imaging modality for diagnosis of neurocutaneous melanosis is Magnetic Resonance Imaging, although ultrasound is another viable option. The signal due melanin deposits in the leptomeninges typical of neurocutaneous melanosis can be easily detected in MRI scans of patients under four months old. In patients above this age, there is some suggestion that normal brain myelination may partially obscure these signals.

As most patients with neurocutaneous melanosis are asymptomatic, those who are diagnosed through MR imaging are not guarantied to develop symptoms. Those diagnosed who did not develop symptoms ranged from 10% to 68%. This wide range is most likely due to the large number of asymptomatic, undiagnosed patients with neurocutaneous melanosis.

A 2007 study followed 112 individuals for a mean of 12 years (mean age 25.3, range 12–71). No patient died during follow-up, but several required medical interventions. The mean final heights were 167 and 153 cm for men and women, respectively, which is approximately 2 standard deviations below normal.

First trimester ultrasound of noonan syndrome reveals nuchal oedema / cystic hygroma almost same as seen in Turner syndrome. Follow up scans may shows clinical features that already described above.

A study shows this disease is also associated with hepato splenomegaly with renal anomalies including malrotation and solitary kidney. A rare incidence of choledochal cyst is also reported as well.

CCD may be detectable on prenatal ultrasound. After birth, signs in affected babies typically are abdominal distension, visible peristalsis, and watery stools persistent from birth that show chloride loss of more than 90 mmol/l.

An important feature in this diarrhea that helps in the diagnosis, is that it is the only type of diarrhea that causes metabolic alkalosis rather than metabolic acidosis.

The majority of patients with neurocutaneous melanosis are asymptomatic and therefore have a good prognosis with few complications. Most are not diagnosed, so definitive data in not available. For symptomatic patients, the prognosis is far worse. In patients without the presence of melanoma, more than 50% die within 3 years of displaying symptoms. While those with malignancy have a mortality rate of 77% with most patients displaying symptoms before the age of 2.

The presence of a Dandy-Walker malformation along with neurocutaneous melanosis, as occurs in 10% of symptomatic patients, further deteriorates prognosis. The median survival time for these patients is 6.5 months after becoming symptomatic.

Studies suggest that prenatal care for mothers during their pregnancies can prevent congenital amputation. Knowing environmental and genetic risks is also important. Heavy exposure to chemicals, smoking, alcohol, poor diet, or engaging in any other teratogenic activities while pregnant can increase the risk of having a child born with a congenital amputation. Folic acid is a multivitamin that has been found to reduce birth defects.

For most cases the diagnosis for congenital amputation is not made until the infant is born. One procedure that is helpful in determining this condition in an infant is an ultrasound examination of a fetus when still in the mother's abdomen as it can reveal the absence of a limb. However, since ultrasounds are routine they may not pick up all the signs of some of the more subtle birth defects.

The most popular method of treatment for congenital amputation is having the child be fit for a prosthesis which can lead to normal development, so the muscles don't atrophy. If there is congenital amputation of the fingers, plastic surgery can be performed by using the big toe or second toes in place of the missing fingers of the hand.

In rare cases of amniotic banding syndrome, if diagnosed "in utero", fetal surgery may be considered to save a limb which is in danger of amputation.

The only treatment for MWS is only symptomatic, with multidisciplinary management

In terms of the investigation of congenital hyperinsulinism, valuable diagnostic information is obtained from a blood sample drawn during hypoglycemia, detectable amounts of insulin during hypoglycemia are abnormal and indicate that hyperinsulinism is likely to be the cause. Inappropriately low levels of free fatty acids and ketones provide additional evidence of insulin excess. An additional piece of evidence indicating hyperinsulinism is a usually high requirement for intravenous glucose to maintain adequate glucose levels, the minimum glucose required to maintain a plasma glucose above 70 mg/dl. A GIR above 8 mg/kg/minute in infancy suggests hyperinsulinism. A third form of evidence suggesting hyperinsulinism is a rise of the glucose level after injection of glucagon at the time of the low glucose.

Diagnostic efforts then shift to determining the type- elevated ammonia levels or abnormal organic acids can indicate specific, rare types. Intrauterine growth retardation and other perinatal problems raise the possibility of transience, while large birthweight suggests one of the more persistent conditions. Genetic screening is now available within a useful time frame for some of the specific conditions.It is worthwhile to identify the minority of severe cases with focal forms of hyperinsulinism because these can be completely cured by partial pancreatectomy. A variety of pre-operative diagnostic procedures have been investigated but none has been established as infallibly reliable. Positron emission tomography is becoming the most useful imaging technique.