Cardiomyopathy, and Osteoporosis

Low match HEMOCHROMATOSIS TYPE 2

Hemochromatosis type 2 (juvenile) is the early-onset and most severe form of rare hereditary hemochromatosis (HH; see this term), a group of diseases characterized by excessive tissue iron deposition of genetic origin.

HEMOCHROMATOSIS TYPE 2 Is also known as juvenile hemochromatosis

• Muscle weakness
• Pain
• Hypertension
• Hepatomegaly
• Cardiomyopathy

SOURCES: OMIM ORPHANET MENDELIAN

Low match JUNCTIONAL EPIDERMOLYSIS BULLOSA, GENERALIZED SEVERE

Junctional epidermolysis bullosa, Herlitz-type is a severe subtype of junctional epidermolysis bullosa (JEB, see this term) characterized by blisters and extensive erosions, localized to the skin and mucous membranes.

JUNCTIONAL EPIDERMOLYSIS BULLOSA, GENERALIZED SEVERE Is also known as epidermolysis bullosa letalis|junctional epidermolysis bullosa, herlitz type|junctional epidermolysis bullosa, herlitz-pearson type|jeb-herlitz type|jeb-h|epidermolysis bullosa junctionalis, herlitz type|epidermolysis bullosa, junctional, herlitz-pearson

• Failure to thrive
• Anemia
• Feeding difficulties
• Respiratory insufficiency
• Syndactyly

SOURCES: OMIM ORPHANET MENDELIAN

Low match AUTOSOMAL RECESSIVE LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE 2E

Autosomal recessive limb girdle muscular dystrophy type 2E (LGMD2E) is a subtype of autosomal recessive limb girdle muscular dystrophy characterized by a childhood to adolescent onset of progressive pelvic- and shoulder-girdle muscle weakness, particularly affecting the pelvic girdle (adductors and flexors of hip). Usually the knees are the earliest and most affected muscles. In advanced stages, involvement of the shoulder girdle (resulting in scapular winging) and the distal muscle groups are observed. Calf hypertrophy, cardiomyopathy, respiratory impairment, tendon contractures, scoliosis, and exercise-induced myoglobinuria may be observed.

AUTOSOMAL RECESSIVE LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE 2E Is also known as beta-sarcoglycanopathy|limb-girdle muscular dystrophy due to beta-sarcoglycan deficiency|lgmd2e|muscular dystrophy, limb-girdle, type 2e

• Scoliosis
• Delayed speech and language development
• Gait disturbance
• Dysphagia
• Respiratory insufficiency

SOURCES: ORPHANET OMIM MENDELIAN

Low match BETA-THALASSEMIA

Beta-thalassemia is characterized by a reduced production of hemoglobin A (HbA, alpha-2/beta-2), which results from the reduced synthesis of beta-globin chains relative to alpha-globin chains, thus causing an imbalance in globin chain production and hence abnormal erythropoiesis. The disorder is clinically heterogeneous (summary by Ottolenghi et al., 1975).Absence of beta globin causes beta-zero-thalassemia. Reduced amounts of detectable beta globin causes beta-plus-thalassemia. For clinical purposes, beta-thalassemia is divided into thalassemia major (transfusion dependent), thalassemia intermedia (of intermediate severity), and thalassemia minor (asymptomatic, carrier state). The molecular and clinical aspects of the beta-thalassemias were reviewed by Olivieri (1999).The remarkable phenotypic diversity of the beta-thalassemias reflects the heterogeneity of mutations at the HBB locus, the action of many secondary and tertiary modifiers, and a wide range of environmental factors (Weatherall, 2001).

• Growth delay
• Failure to thrive
• Muscle weakness
• Anemia
• Feeding difficulties

SOURCES: OMIM ORPHANET MENDELIAN

Low match SYMPTOMATIC FORM OF HEMOCHROMATOSIS TYPE 1

Symptomatic form of hemochromatosis type 1 is a rare, hereditary hemochromatosis characterized by inappropriately regulated intestinal iron absorption which leads to excessive iron storage in various organs and manifests with a wide range of signs and symptoms, including abdominal pain, weakness, lethargy, weight loss, elevated serum aminotransferase levels, increase in skin pigmentation, and/or arthropathy in the metacarpophalangeal joints. Other commonly associated manifestations include hepatomegaly, cirrhosis, liver fibrosis, hepatocellular carcinoma, restrictive cardiomyopathy and/or diabetes mellitus.

SYMPTOMATIC FORM OF HEMOCHROMATOSIS TYPE 1 Is also known as symptomatic form of hfe-related hereditary hemochromatosis|symptomatic form of classic hemochromatosis

• Peripheral neuropathy
• Hepatomegaly
• Fatigue
• Cardiomyopathy
• Congestive heart failure

SOURCES: ORPHANET MENDELIAN

Low match DYSKERATOSIS CONGENITA, AUTOSOMAL DOMINANT 2; DKCA2

Dyskeratosis congenita is a multisystem disorder caused by defective telomere maintenance. Features are variable and include bone marrow failure, pulmonary and liver fibrosis, and premature graying of the hair (summary by Armanios et al., 2005).For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (OMIM ).

• Global developmental delay
• Short stature
• Microcephaly
• Growth delay
• Failure to thrive

SOURCES: OMIM MENDELIAN

Low match SEVERE GENERALIZED RECESSIVE DYSTROPHIC EPIDERMOLYSIS BULLOSA

Severe generalized recessive dystrophic epidermolysis bullosa (RDEB-sev gen) is the most severe subtype of dystrophic epidermolysis bullosa (DEB, see this term), formerly known as the Hallopeau-Siemens type, and is characterized by generalized cutaneous and mucosal blistering and scarring associated with severe deformities and major extracutaneous involvement.

SEVERE GENERALIZED RECESSIVE DYSTROPHIC EPIDERMOLYSIS BULLOSA Is also known as rdeb, hallopeau-siemens type|severe generalized rdeb|dystrophic epidermolysis bullosa, autosomal recessive|rdeb generalisata gravis|epidermolysis bullosa dystrophica, hallopeau-siemens type|rdeb-sev gen|autosomal recessive dystrophic epidermolysis bullosa

• Growth delay
• Neoplasm
• Cataract
• Anemia
• Flexion contracture

SOURCES: ORPHANET OMIM MENDELIAN

Low match HEMOCHROMATOSIS, TYPE 1; HFE1

Hereditary hemochromatosis is an autosomal recessive disorder of iron metabolism wherein the body accumulates excess iron (summary by Feder et al., 1996). Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading. Removal of excess iron by therapeutic phlebotomy decreases morbidity and mortality if instituted early in the course of the disease. Classic hemochromatosis (HFE) is most often caused by mutation in a gene designated HFE on chromosome 6p21.3.Adams and Barton (2007) reviewed the clinical features, pathophysiology, and management of hemochromatosis. Genetic Heterogeneity of HemochromatosisAt least 4 additional iron overload disorders labeled hemochromatosis have been identified on the basis of clinical, biochemical, and genetic characteristics. Juvenile hemochromatosis, or hemochromatosis type 2 (HFE2), is autosomal recessive and is divided into 2 forms: HFE2A (OMIM ), caused by mutation in the HJV gene (OMIM ) on chromosome 1q21, and HFE2B (OMIM ), caused by mutation in the HAMP gene (OMIM ) on chromosome 19q13. Hemochromatosis type 3 (HFE3 ), an autosomal recessive disorder, is caused by mutation in the TFR2 gene (OMIM ) on chromosome 7q22. Hemochromatosis type 4 (HFE4 ), an autosomal dominant disorder, is caused by mutation in the SLC40A1 gene (OMIM ) on chromosome 2q32. Hemochromatosis type 5 (HFE5 ) is caused by mutation in the FTH1 gene (OMIM ) on chromosome 11q12.

HEMOCHROMATOSIS, TYPE 1; HFE1 Is also known as hfe|hemochromatosis, hereditary|hemochromatosis|hh

• Ataxia
• Neoplasm
• Pain
• Anemia
• Hepatomegaly

SOURCES: ORPHANET OMIM MENDELIAN

Low match CUSHING DISEASE

Cushing disease (CD) is the most common cause of endogenous Cushing syndrome (CS; see this term) and is due to pituitary chronic over-secretion of ACTH by a pituitary corticotroph adenoma.

CUSHING DISEASE Is also known as corticotroph pituitary adenoma|pituitary-dependent cushing syndrome|pituitary corticotroph micro-adenoma

• Failure to thrive
• Cataract
• Visual impairment
• Hypertension
• Fatigue

SOURCES: ORPHANET MENDELIAN

Low match DILATED CARDIOMYOPATHY-HYPERGONADOTROPIC HYPOGONADISM SYNDROME

This syndrome is characterized by the association of dilated cardiomyopathy and hypergonadotropic hypogonadism (DCM-HH).

DILATED CARDIOMYOPATHY-HYPERGONADOTROPIC HYPOGONADISM SYNDROME Is also known as cardiomyopathy, dilated, with premature ovarian failure|genital anomaly with cardiomyopathy|najjar syndrome|cardiomyopathy, congestive, with hypergonadotropic hypogonadism|cardiogenital syndrome|cardiomyopathy with primary testicular failure|malouf syndro

• Intellectual disability
• Short stature
• Scoliosis
• Cryptorchidism
• Ptosis

SOURCES: OMIM ORPHANET MENDELIAN