Medullary cystic kidney disease type 1 (MCKD1) is an inherited condition that affects the kidneys. It leads to scarring (fibrosis) and impaired function of the kidneys, usually beginning in adulthood. The kidneys filter fluid and waste products from the body. They also reabsorb needed nutrients and release them back into the blood. As MCKD1 progresses, the kidneys are less able to function, resulting in kidney failure. Declining kidney function in people with MCKD1 leads to the signs and symptoms of the condition.

A number sign (#) is used with this entry because of evidence that autosomal dominant medullary cystic kidney disease-1 (MCKD1) is caused by heterozygous mutation in the MUC1 gene (158340) on chromosome 1q22. Description Medullary cystic kidney disease (MCKD) is an autosomal dominant form of tubulointerstitial nephropathy characterized by formation of renal cysts at the corticomedullary junction. It is characterized by adult onset of impaired renal function and salt wasting resulting in end-stage renal failure by the sixth decade (Wolf et al., 2004). Although early reports suggested that medullary cystic kidney disease and familial juvenile nephronophthisis (NPHP1; 256100) represented the same disease entity because of the overlapping phenotype (Chamberlin et al., 1977), they are now considered to be distinct disorders. MCKD has adult onset and shows autosomal dominant inheritance, whereas NPHP1 has juvenile onset and shows autosomal recessive inheritance (Christodoulou et al., 1998).

Autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations (ADTKD-MUC1) is an inherited disorder that causes a gradual loss of kidney function. This may lead to the need for dialysis or kidney transplant usually between the ages of 30 and 70. This condition is not associated with any symptoms outside of the kidney. ADTKD-MUC1 is caused by a mistake (mutation) in the MUC1 gene that leads to production of an abnormal mucin 1 protein, which deposits in the kidney and leads to slow loss of kidney function ADTKD-MUC1 is inherited in families in an autosomal dominant pattern. It is diagnosed based on laboratory testing, family history and genetic testing.

Summary Clinical characteristics. Autosomal dominant tubulointerstitial kidney disease, MUC1 -related (ADTKD- MUC1 ) was previously known as medullary cystic kidney disease type 1. It is characterized by slowly progressive tubulointerstitial disease that leads to end-stage renal disease (ESRD) and the need for dialysis or kidney transplantation. ESRD typically occurs in adulthood but is extremely variable, occurring at any age between 20 and 70 years. There are no other systemic manifestations. Diagnosis/testing. Diagnosis of ADTKD- MUC1 is suspected in individuals with an elevated serum creatinine, bland urinary sediment (i.e., little blood or protein), and a family history of kidney disease inherited in an autosomal dominant manner. Renal ultrasound examination may reveal normal or small kidneys. Renal biopsy findings are nonspecific (and, hence, not diagnostic).

X-linked recessive disorder characterised by developmental delay Say–Meyer syndrome Other names Trigonocephaly-short stature-developmental delay syndrome Say–Meyer syndrome is inherited in an X-linked recessive manner. Say–Meyer syndrome is a rare X-linked genetic disorder that is mostly characterized as developmental delay . It is one of the rare causes of short stature . It is closely related with trigonocephaly (a misshapen forehead due to premature fusion of bones in the skull). People with Say–Meyer syndrome have impaired growth, deficits in motor skills development and mental state. [1] [2] It is suggested that it is from a X-linked transmission. [3] Contents 1 Signs and symptoms 1.1 Growth and development 2 Causes 3 Diagnosis 4 Treatment 4.1 Surgical 5 History 6 References 7 External links Signs and symptoms [ edit ] Common signs of Say–Meyer syndrome are trigonocephaly as well as head and neck symptoms. The head and neck symptoms come in the form of craniosynostosis affecting the metopic suture (the dense connective tissue structure that divides the two halves of the skull in children which usually fuse together by the age of six).

A rare developmental defect during embryogenesis characterized by premature closure of metopic sutures and/or other sutures, short stature, and developmental delay. Dysmorphic features include trigonocephaly, metopic ridge, narrow forehead, bitemporal narrowing, arched eyebrows, hypotelorism, deep-set eyes, epicanthal folds, strabismus, wide nasal bridge, small pointed nose, anteverted nostrils, long philtrum, low-set ears, malar flattening, narrow mouth, thin lips, high-arched palate, crowded teeth, and micrognathia. Variable additional manifestations may include conductive hearing loss, cerebral (mainly involving the white matter), skeletal (e.g. brachymesophalangy of the fifth fingers), cardiovascular and renal anomalies, inguinal hernia, hypospadias, and seizures.

A number sign (#) is used with this entry because afibrinogenemia is caused by homozygous or compound heterozygous mutation in one or another of the 3 fibrinogen genes: alpha (FGA; 134820), beta (FGB; 134830), or gamma (FGG; 134850). Hypofibrinogenemia is most often caused by heterozygous mutation, but also by homozygous or compound heterozygous mutation, in one of these genes. Description Inherited disorders of fibrinogen affect either the quantity (afibrinogenemia and hypofibrinogenemia; 202400) or the quality (dysfibrinogenemia; 616004) of the circulating fibrinogen or both (hypodysfibrinogenemia; see 616004). Afibrinogenemia is characterized by the complete absence of immunoreactive fibrinogen. Bleeding due to afibrinogenemia usually manifests in the neonatal period, with 85% of cases presenting umbilical cord bleeding, but a later age of onst is not unusual.

Congenital afibrinogenemia is a bleeding disorder caused by impairment of the blood clotting process. Normally, blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss. However, bleeding is uncontrolled in people with congenital afibrinogenemia. Newborns with this condition often experience prolonged bleeding from the umbilical cord stump after birth. Nosebleeds (epistaxis) and bleeding from the gums or tongue are common and can occur after minor trauma or in the absence of injury (spontaneous bleeding).

Afibrinogenemia , sometimes called congenital afibrinogenemia, is an inherited blood disorder in which the blood does not clot normally. It occurs when there is a lack (deficiency) of a protein called fibrinogen (or coagulation factor I), which is needed for the blood to clot. Affected individuals may be susceptible to severe bleeding (hemorrhaging) episodes, particularly during infancy and childhood. Afibrinogenemia is thought to be transmitted as an autosomal recessive trait. Treatment may include cryoprecipitate (a blood product containing concentrated fibrinogen and other clotting factors), fibrinogen concentrates or plasma (the liquid portion of the blood which contains clotting factors).

Familial afibrinogenemia is a coagulation disorder characterized by bleeding symptoms due to a complete absence of circulating fibrinogen. Epidemiology Prevalence of afibrinogenemia is estimated at 1/1,000,000. 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. Etiology The deficiency is due to various mutations in the FGA , FGB , or FGG genes. Genetic counseling Transmission is autosomal recessive.

Congenital hypofibrinogenemia Specialty Hematology Congenital hypofibrinogenemia is a rare disorder in which one of the two genes responsible for producing fibrinogen , a critical blood clotting factor , is unable to make a functional fibrinogen glycoprotein because of an inherited mutation . In consequence, liver cells, the normal site of fibrinogen production, make small amounts of this critical coagulation protein, blood levels of fibrinogen are low, and individuals with the disorder may suffer a coagulopathy , i.e. a diathesis or propensity to experience episodes of abnormal bleeding. However, individuals with congenital hypofibringenemia may also suffer episodes of abnormal blood clot formation, i.e. thrombosis . This seemingly paradoxical propensity to develop thrombosis in a disorder causing a decrease in a critical protein for blood clotting may be due to the function of fibrin (the split product of fibrinogen that is the basis for forming blood clots) to promote the lysis or disintegration of blood clots. Lower levels of fibrin may reduce the lysis of early fibrin strand depositions and thereby allow these depositions to develop into clots. [1] Congenital hypofibrinogenemia must be distinguished from: a) congenital afibrinogenemia , a rare disorder in which blood fibrinogen levels are either exceedingly low or undetectable due to mutations in both fibrinogen genes; b) congenital hypodysfibrinogenemia , a rare disorder in which one or more genetic mutations cause low levels of blood fibrinogen, at least some of which is dysfunctional and thereby contributes to excessive bleeding; and c) acquired hypofibrinogenemia, a non-hereditary disorder in which blood fibrinogen levels are low because of e.g. severe liver disease or because of excessive fibrinogen consumption resulting from, e.g. disseminated intravascular coagulation . [1] [2] Certain gene mutations causing congenital hypfibrinogenemia disrupt the ability of liver cells to secrete fibrinogen.

Familial hypofibrinogenemia is a coagulation disorder characterized by mild bleeding symptoms following trauma or surgery due to a reduced plasma fibrinogen concentration. Epidemiology Prevalence is unknown but hypofibrinogenemia is more frequent than afibrinogenemia which has a prevalence of 1/1,000,000. Etiology The deficiency is due to various mutations in the FGA , FGB , or FGG genes. Genetic counseling Transmission is mainly autosomal dominant.

Leukoencephalopathy-dystonia-motor neuropathy syndrome is a peroxisomal neurodegenerative disorder characterized by spasmodic torticollis, dystonic head tremor, intention tremor, nystagmus, hyposmia, and hypergonadotrophic hypogonadism with azoospermia. Slight cerebellar signs (left-sided intention tremor, balance and gait impairment) are also noted. Magnetic resonance imaging (MRI) shows bilateral hyperintense signals in the thalamus, butterfly-like lesions in the pons, and lesions in the occipital region, whereas nerve conduction studies of the lower extremities shows a predominantly motor and slight sensory neuropathy.

A number sign (#) is used with this entry because susceptibility to multiple self-healing squamous epithelioma (MSSE) is conferred by heterozygous loss-of-function mutation in the TGFBR1 gene (190181) on chromosome 9q22. Description Individuals with multiple self-healing squamous epithelioma (MSSE) develop multiple invasive skin tumors that undergo spontaneous regression leaving pitted scars. Age at onset is highly variable, ranging from 8 to 62 years. The disorder shows autosomal dominant inheritance, and most affected families have originated from western Scotland (Bose et al., 2006). MSSE has been considered to be a variety of multiple keratoacanthoma (Biskind et al., 1957; Haydey et al., 1980). Clinical Features Ferguson Smith (1934) first described this disorder in a single case, that of a 23-year-old miner, who first developed spots on the legs at age 16 years.

Multiple familial keratoacanthoma (KA) of Witten and Zak is a rare a rare inherited skin cancer syndrome and is characterized by the coexistence of features characteristic of both multiple KA, Ferguson Smith type and generalized eruptive keratoacanthoma (see these terms), such as multiple small miliary-type lesions, larger self-healing lesions, and nodulo-ulcerative lesions .Lesions do not have a predilection for the mucosal surfaces. Transmission is autosomal dominant.

Avascular necrosis of the femoral head (ANFH) is a degenerative condition which causes the upper ends of the thigh bones (femurs) to break down due to a disrupted blood supply and poor bone repair. It can lead to pain and limping, hip collapse, and cause the legs to be of unequal length. The development of ANFH is associated with steroid use, alcohol use, smoking, auto-immune disorders, and other medical conditions such as sickle cell anemia. Less commonly, ANFH can occur as the result of trauma to the hip, such as a hip fracture or hip surgery. Around 20,000-30,000 cases are reported each year in the United States.

A number sign (#) is used with this entry because of evidence that familial avascular necrosis of the femoral head-1 (ANFH1) is caused by heterozygous mutation in the COL2A1 gene (120140) on chromosome 12q13. Description Avascular necrosis of the femoral head (ANFH) is a debilitating disease that usually leads to destruction of the hip joint in the third to fifth decade of life. The disorder is characterized by progressive pain in the groin, mechanical failure of the subchondral bone, and degeneration of the hip joint. Nearly one-half of patients require hip replacement before 40 years of age. ANFH represents a specific form of the broader disease category of osteonecrosis (summary by Mont and Hungerford, 1995).

Dianzani autoimmune lymphoproliferative disease (DALD) is a very rare disorder characterized by autoimmunity, lymphadenopathy and/or splenomegaly. Epidemiology The prevalence of DALD is not known. The disorder has been reported in fewer than 30 patients to date. Clinical description Age of onset is highly variable, ranging from childhood to young adulthood. In patients with DALD, signs of autoimmunity include recurrent episodes of thrombocytopenia, neutropenia, and/or autoimmune hemolytic anemia. Lymphoadenopathy and/or splenomegaly are invariably noted. A possible increased risk of cancer has been suggested in these patients.