3308
(4.0%)

Chromophobe renal cell carcinoma

Hypospadias

Chromophobe renal cell carcinoma is a rare subtype of renal cell carcinoma, originating from the intercalating cells of the collecting ducts and macroscopically manifesting as a well-circumscribed, highly lobulated, solid tumor that is usually diagnosed at an early stage. It is frequently asymptomatic, or may present with nonspecific symptoms, such as weight loss, fever or fatigue. The classic presentation observed in renal tumors (hematuria, flank pain and palpable mass) is occasionally observed and usually indicates an advanced stage of the disease. It is most frequently sporadic however, several familial cases, associated with Birt-Hogg Dubé syndrome, have been described.

3308
(4.0%)

Frasier syndrome

Ambiguous genitalia, male

Autosomal dominant inheritance Somatic mutation

Frasier syndrome is characterised by the association of male pseudohermaphrodism and glomerular nephropathy. This syndrome is associated with a high risk of developing gonadoblastoma.

3308
(4.0%)

Hyperinsulinism due to HNF1A deficiency

Agitation

Hyperinsulinism due to HNF1A deficiency is a form of diazoxide-sensitive diffuse hyperinsulinism (DHI), characterized by transient or persistent hyperinsulinemic hypoglycemia (HH) in infancy that is responsive to diazoxide, evolving in to maturity-onset diabetes of the young subtype 1 (MODY-1; see this term) later in life.

3308
(4.0%)

Mitochondrial membrane protein-associated neurodegeneration

Urinary incontinence

Autosomal recessive inheritance

Mitochondrial membrane protein-sssociated neurodegeneration (MPAN), also known as neurogeneration with brain iron accumulation (NBIA) due to C19orf12 mutations, is an autosomal recessive neurodegenerative disorder characterized by iron accumulation in specific regions of the brain, usually the basal ganglia, and associated with slowly progressive pyramidal (spasticity) and extrapyramidal (dystonia) signs, motor axonal neuropathy, optic atrophy, cognitive decline, and neuropsychiatric abnormalities.

3308
(4.0%)

Pituitary stalk interruption syndrome

Cryptorchidism

Pituitary stalk interruption syndrome (PSIS) is a congenital abnormality of the pituitary that is responsible for pituitary deficiency and is usually characterized by the triad of a very thin or interrupted pituitary stalk, an ectopic (or absent) posterior pituitary (EPP) and hypoplasia or aplasia of the anterior pituitary visible on MRI. In some patients the abnormality may be limited to EPP (also called ectopic neurohypophysis) or to an interrupted pituitary stalk.

3308
(4.0%)

Isovaleric acidemia

Albinism

Autosomal recessive inheritance

An autosomal recessively inherited organic aciduria characterized by a deficiency in isovaleryl-CoA dehydrogenase, that has wide clinical variability and that can present in infancy with acute manifestations of vomiting, failure to thrive, seizures, lethargy, a characteristic ''sweaty feet'' odor, acute pancreatitis and mild to severe developmental delay or in childhood with metabolic acidosis (brought on by prolonged fasting, an increased intake of protein-rich food or infections) and that can be fatal if not treated immediately. Chronic intermittent presentations and asymptomatic patients have also been reported.

3308
(4.0%)

Autosomal recessive spastic paraplegia type 11

Cataract

Autosomal recessive inheritance

A complex hereditary spastic paraplegia characterized by progressive lower limbs weakness and spasticity, upper limbs weakness, dysarthria, hypomimia, sphincter disturbances, peripheral neuropathy, learning difficulties, cognitive impairment and dementia. Magnetic resonance imaging shows thin corpus callosum, cerebral atrophy, and periventricular white matter changes.

3308
(4.0%)

Medium chain acyl-CoA dehydrogenase deficiency

Cyanosis

Autosomal recessive inheritance

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD) is an inborn error of mitochondrial fatty acid oxidation characterized by a rapidly progressive metabolic crisis, often presenting as hypoketotic hypoglycemia, lethargy, vomiting, seizures and coma, which can be fatal in the absence of emergency medical intervention.

3308
(4.0%)

Thiamine-responsive megaloblastic anemia syndrome

Sensorineural hearing impairment

Autosomal recessive inheritance

Thiamine-responsive megaloblastic anemia (TRMA) is characterized by a triad of megaloblastic anemia, non-type I diabetes mellitus, and sensorineural deafness.

3308
(4.0%)

Pituicytoma

Hypogonadotropic hypogonadism

3308
(4.0%)

Meacham syndrome

Cryptorchidism

Meacham syndrome is a multiple malformation syndrome characterized by congenital diaphragmatic abnormalities, genital defects and cardiac malformations.

3308
(4.0%)

Mitral atresia

Ambiguous genitalia

3308
(4.0%)

Denys-Drash syndrome

Cryptorchidism

Autosomal dominant inheritance Somatic mutation

A rare urogenital disorder characterized by the association of diffuse mesangial sclerosis (DMS), male pseudohermaphroditism with a 46,XY karyotype, and nephroblastoma.

3308
(4.0%)

Situs ambiguus

Coloboma

A rare, genetic, developmental defect during embryogenesis characterized by a partial mirror-image transposition of intra-thoracic and/or intra-abdominal organs across the left-right axis of the body. Intra-organ variations and other malformations, such as ciliary motricity anomalies (e.g. Kartagener syndrome), biliary atresia and cardiac defects, are frequently associated. Left (polysplenia syndrome) or right (asplenia syndrome) isomerism are usually observed.

3308
(4.0%)

Methanol poisoning

Visual impairment

Methanol poisoning is a rare poisoning resulting in elevated anion gap metabolic acidosis, due to the alcohol dehydrogenase (ADH)-mediated production of formic acid (which is poisonous to the central nervous system), and characterized by dizziness, nausea, vomiting, confusion, metabolic acidosis, visual disturbances (which if left untreated can lead to blindness), coma, and death (due to respiratory failure).

3308
(4.0%)

Lymphomatoid papulosis

Proteinuria

Lymphomatoid papulosis (LyP) is a rare cutaneous condition characterized by chronic, recurrent, and self-regressing papulonodular skin eruptions. It belongs to the spectrum of primary cutaneous CD30+ lymphoproliferative disorders, along with primary cutaneous anaplastic large cell lymphoma (primary C-ALCL; see this term) with which it shares overlapping clinical and histopathologic features.

3308
(4.0%)

Childhood absence epilepsy

Urinary incontinence

Autosomal dominant inheritance Heterogeneous

Childhood absence epilepsy (CAE) is a familial generalized pediatric epilepsy, characterized by very frequent (multiple per day) absence seizures, usually occurring in children between the ages of 4 and 10 years, with, in most cases, a good prognosis.

3308
(4.0%)

Autosomal dominant cerebellar ataxia-deafness-narcolepsy syndrome

Urinary incontinence

Autosomal dominant inheritance

A rare polymorphic disorder, subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1), characterized by ataxia, sensorineural deafness and narcolepsy with cataplexy and dementia.

3308
(4.0%)

Juvenile Huntington disease

Behavioral abnormality

Juvenile Huntington disease (JHD) is a form of Huntington disease (HD; see this term), characterized by onset of signs and symptoms before 20 years of age.

3308
(4.0%)

Apparent mineralocorticoid excess

Renal insufficiency

Autosomal recessive inheritance

A rare form of pseudohyperaldosteronism characterized by very early-onset and severe hypertension, associated with low renin levels and hypoaldosteronism.

3308
(4.0%)

Tracheal agenesis

Horseshoe kidney

Tracheal agenesis (TA) is a rare congenital malformation in which the trachea may be completely absent (agenesis), or partially in place but underdeveloped (atresia). In both cases, proximal-distal communication between the larynx and the alveoli of the lungs is lacking.

3308
(4.0%)

Pure autonomic failure

Urinary incontinence

Pure autonomic failure (PAF) is a neurodegenerative disease that affects the sympathetic branch of the autonomous nervous system and that manifests with orthostatic hypotension.

3308
(4.0%)

Glycogen storage disease due to LAMP-2 deficiency

Autism

X-linked recessive inheritance X-linked dominant inheritance

Glycogen storage disease due to LAMP-2 (Lysosomal-Associated Membrane Protein 2) deficiency is a lysosomal glycogen storage disease characterised by severe cardiomyopathy and variable degrees of muscle weakness, frequently associated with intellectual deficit.

3308
(4.0%)

Dubin-Johnson syndrome

Jaundice

Autosomal recessive inheritance

Dubin-Johnson syndrome (DJS) is a benign, inherited liver disorder characterized clinically by chronic, predominantly conjugated, hyperbilirubinemia and histopathologically by black-brown pigment deposition in parenchymal liver cells.

3308
(4.0%)

Gliomatosis cerebri

Urinary incontinence

3308
(4.0%)

Alveolar soft tissue sarcoma

Proptosis

Somatic mutation

3308
(4.0%)

Female restricted epilepsy with intellectual disability

Behavioral abnormality

X-linked inheritance

Female restricted epilepsy with intellectual disability is a rare X-linked epilepsy syndrome characterized by febrile or afebrile seizures (mainly tonic-clonic, but also absence, myoclonic, and atonic) starting in the first years of life and, in most cases, developmental delay and intellectual disability of variable severity. Behavioral disturbances (e.g. autistic features, hyperactivity, and aggressiveness) are also frequently associated. This disease affects exclusively females, with male carriers being unaffected, despite an X-linked inheritance.

3308
(4.0%)

Acyl-CoA dehydrogenase 9 deficiency

Generalized hypotonia

Autosomal recessive inheritance

A rare disorder characterized by neurological dysfunction, hepatic failure and cardiomyopathy due to a deficiency of complex I of the respiratory chain.

3308
(4.0%)

Neuroendocrine tumor of the rectum

Hemangioma

Neuroendocrine tumor of the rectum is a rare epithelial tumor of rectum arising from enterochromaffin cells, most often in the mid-rectum. The tumors are slow growing, in early stages majority are asymptomatic and are diagnosed incidentally. Later in the course, the tumor may present with rectal bleeding, abdominal or rectal pain, tenesmus, changes in bowel habits, or weight loss. In some cases it may present with carcinoid symptoms of flushing and increased gut motility.

3308
(4.0%)

Neuroectodermal melanolysosomal disease

Strabismus

Autosomal recessive inheritance

Elejalde syndrome (ES) is characterized by silvery to leaden hair, bronze skin colour in sun-exposed areas and severe neurological impairment.

3308
(4.0%)

Hereditary fructose intolerance

Renal insufficiency

Autosomal recessive inheritance

Hereditary fructose intolerance (HFI) is an autosomal recessive disorder of fructose metabolism (see this term), resulting from a deficiency of hepatic fructose-1-phosphate aldolase activity and leading to gastrointestinal disorders and postprandial hypoglycemia following fructose ingestion. HFI is a benign condition when treated, but it is life-threatening and potentially fatal if left untreated.

3308
(4.0%)

Mounier-Kühn syndrome

Ptosis

Autosomal recessive inheritance

Mounier-Kühn syndrome, also known as idiopathic tracheobronchomegaly, is a congenital disorder characterized by marked dilatation of the trachea and proximal bronchi that leads to impaired airway secretion clearance and recurrent lower respiratory tract infections.

3308
(4.0%)

Vitamin B12-unresponsive methylmalonic acidemia

Renal insufficiency

Autosomal recessive inheritance

Vitamin B12-unresponsive methylmalonic acidemia is an inborn error of vitamin B12 (cobalamin) metabolism characterized by recurrent ketoacidotic crises or transient vomiting, dehydration, hypotonia and intellectual deficit, which does not respond to administration of vitamin B12. There are two types of vitamin B12-unresponsive methylmalonic acidemia: mut0 and mut- (see these terms).

3308
(4.0%)

Gestational choriocarcinoma

Hematuria

Gestational choriocarcinoma is a gestational trophoblastic tumor (GTT; see this term) occurring secondary to pregnancy (ectopic or normal), miscarriage, voluntary termination of pregnancy (VTP) or a hydatidiform mole (see this term).

3308
(4.0%)

Neuroendocrine neoplasm of appendix

Primary hypercortisolism

Endocrine tumor of the appendix is the most common sporadic neoplasm of the appendix and the second most common type of digestive endocrine tumor, often with no specific clinical presentation. They are divided into either classic endocrine tumor of the appendix or the more aggressive goblet cell carcinoma (GCC; see these terms).

3308
(4.0%)

Megacystis-microcolon-intestinal hypoperistalsis syndrome

Multicystic kidney dysplasia

Autosomal dominant inheritance

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare congenital disease characterized by massive abdominal distension caused by a largely dilated non-obstructed urinary bladder (megacystis), microcolon and decreased or absent intestinal peristalsis.

3308
(4.0%)

Drug-induced lupus erythematosus

Hematuria

A rare, systemic disease with skin involvement characterized by the onset of idiopathic lupus erythematosus-like signs and symptoms resulting from continuous drug intake (>1 month), which resolve when treatment is discontinued, in persons with no history of autoimmune disease. Manifestations are variable and may be systemic (e.g. arthralgia, myalgia, fever, fatigue, serositis, pleuritis, pericarditis), subacute cutaneous (incl. photosensitive, non-scarring, annular, polycyclic or papulosquamous lesions, malar erythema, vasculitis, bullous lesions, erythema multiforme-like changes), and/or chronic cutaneous (typically discoid lesions in sun-exposed areas). Procainamide and hydrazaline are the drugs most frequently implicated.

3308
(4.0%)

Hereditary coproporphyria

Behavioral abnormality

Autosomal dominant inheritance

Hereditary coproporphyria is a form of acute hepatic porphyria (see this term) characterized by the occurrence of neuro-visceral attacks and, more rarely, by the presence of cutaneous lesions.

3308
(4.0%)

Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome

Ptosis

Autosomal recessive inheritance

Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome is characterised by adult-onset severe sensory ataxic neuropathy, dysarthria and chronic progressive external ophthalmoplegia.

3308
(4.0%)

Glucocorticoid resistance

Ambiguous genitalia

Autosomal dominant inheritance Autosomal recessive inheritance

3308
(4.0%)

Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality

Purpura

Somatic mutation Autosomal dominant contiguous gene syndrome Sporadic

3308
(4.0%)

Juvenile neuronal ceroid lipofuscinosis

Retinopathy

Juvenile neuronal ceroid lipofuscinoses (JNCLs) are a genetically heterogeneous group of neuronal ceroid lipofuscinoses (NCLs; see this term) typically characterized by onset at early school age with vision loss due to retinopathy, seizures and the decline of mental and motor capacities.

3308
(4.0%)

Deafness-lymphedema-leukemia syndrome

Chronic otitis media

Autosomal dominant inheritance

Deafness - lymphedema - leukemia is a very rare, serious syndromic genetic disorder characterized by primary lymphedema, immunodeficiency, and hematological disorders.

3308
(4.0%)

Sympathetic ophthalmia

Glaucoma

Sympathetic ophthalmia (SO) is a bilateral granulomatous anterior uveitis usually occurring within the three months following trauma or a surgical procedure involving one eye.

3308
(4.0%)

Spinocerebellar ataxia type 10

Urinary urgency

Autosomal dominant inheritance Genetic anticipation

Spinocerebellar ataxia type 10 (SCA10) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by slowly progressive cerebellar syndrome and epilepsy, sometimes mild pyramidal signs, peripheral neuropathy and neuropsychological disturbances.

3308
(4.0%)

Ileal neuroendocrine tumor

Hydronephrosis

Ileal neuroendocrine tumor is a rare, primary, malignant, epithelial neoplasm of the small intestine arising from enterochromaffin cells in the ileum (usually the terminal ileum). Clinical behavior depends on the histologic grade, but initially it is generally characterized by vague abdominal symptoms (cramping, bloating, diarrhea) with insidious onset, although sometimes it could present with signs of bowel obstruction/perforation or gastrointestinal bleeding. Diagnosis in advanced stages with regional or distant spread is common, but signs of carcinoid syndrome (flushing, sweating, diarrhea) are usually not apparent until hepatic metastasis has occurred.

3308
(4.0%)

Early-onset autosomal dominant Alzheimer disease

Abnormality of vision

Early-onset autosomal dominant Alzheimer disease (EOAD) is a progressive dementia with reduction of cognitive functions. EOAD presents the same phenotype as sporadic Alzheimer disease (AD) but has an early age of onset, usually before 60 years old.

3308
(4.0%)

Secondary short bowel syndrome

Primary hypothyroidism

Secondary short bowel syndrome is an intestinal failure caused by any condition that results in a functional small intestine of less than 200 cm in length and is characterized by diarrhea, nutrient malabsoption, bowel dilation and dysmobility.

3308
(4.0%)

Congenital pulmonary airway malformation

Diabetes mellitus

3308
(4.0%)

Cancer-associated retinopathy

Retinopathy

Cancer associated retinopathy (CAR) is a paraneoplastic disease of the eye associated with the presence of extraocular malignancy and circulating autoantibodies against retinal proteins.

3308
(4.0%)

Huntington disease

Behavioral abnormality

Autosomal dominant inheritance

Huntington disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia.

3308
(4.0%)

T-B+ severe combined immunodeficiency due to gamma chain deficiency

Jaundice

X-linked recessive inheritance

Severe combined immunodeficiency (SCID) due to gamma chain deficiency, also called SCID-X1, is a form of SCID (see this term) characterized by severe and recurrent infections, associated with diarrhea and failure to thrive.

3308
(4.0%)

Fatty acid hydroxylase-associated neurodegeneration

Strabismus

Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a very rare, autosomal recessive form of neurodegeneration with brain iron accumulation (NBIA) characterized by childhood-onset focal dystonia, progressive spastic paraplegia that progresses to tetra paresis, ataxia, dysarthria, intellectual decline, and oculomotor disturbances (optic atrophy), accompanied by iron deposition in the globus pallidus.

3308
(4.0%)

Leigh syndrome with leukodystrophy

Hearing impairment

3308
(4.0%)

Reversible cerebral vasoconstriction syndrome

Hypertension

Reversible cerebral vasoconstriction syndrome (RCVS) is an infrequent cerebrovascular disorder characterized by severe headaches with or without focal neurological deficits or seizures, and a reversible segmental and multifocal vasoconstriction of cerebral arteries.

3308
(4.0%)

Differentiated thyroid carcinoma

Diplopia

Differentiated thyroid carcinoma (DTC), also known as papillary or follicular thyroid carcinoma, is a slow-growing malignancy usually presenting in adults as an asymptomatic thyroid mass.

3308
(4.0%)

Carcinoma of the ampulla of Vater

Hydroureter

Carcinoma of the ampulla of Vater is a rare malignant tumor originating from the ampulla of Vater that can present with symptoms of general fatigue, loss of appetite, weight loss, nausea, vomiting, abdominal pain and, most commonly, painless obstructive jaundice. The tumor is believed to arise from duodenal, biliary or pancreatic epilthelium, resulting in the respective histological types. In general, carcinoma of the ampulla of Vater has a better prognosis (5-year survival rate of 45%) than cancers of the distal bile duct and pancreas.

3308
(4.0%)

Papillary renal cell carcinoma

Horseshoe kidney

Papillary renal cell carcinoma is a rare subtype of renal cell carcinoma, arising from the renal tubular epithelium and showing a papillary growth pattern, which typically manifests with hematuria, flank pain, palpable abdominal mass or nonspecific symptoms, such as fatigue, weight loss or fever. Symptoms related to metastatic spread, such as bone pain or persistent cough, are frequently associated since early diagnosis is not common. It is typically multifocal, bilateral, and in most cases sporadic, although different hereditary syndromes, such as Hereditary leiomyoma renal cell carcinoma, Birt-Hogg-Dubé syndrome and Tuberous sclerosis, may predispose to the development of papillary renal cell carcinoma.

3308
(4.0%)

Acquired idiopathic sideroblastic anemia

Hypertension

A rare myelodysplastic syndrome (MDS) characterized by ineffective hemopoiesis affecting one or more blood cell lineages (myeloid, erythroid or megakaryocytic) leading to peripheral blood cytopenias and an increased risk of developing leukaemia.

3308
(4.0%)

Long chain acyl-CoA dehydrogenase deficiency

Autistic behavior

3308
(4.0%)

Corticobasal syndrome

Behavioral abnormality

Corticobasal syndrome (CBS) is a rare neurodegenerative disease characterized by multifaceted motor system dysfunctions and cognitive defects such as asymmetric rigidity, bradykinesia, limb apraxia, and visuospatial dysfunction.

3308
(4.0%)

PPoma

Abnormality of the thyroid gland

PPoma is a type of pancreatic endocrine tumor (see this term) that hypersecretes pancreatic polypeptide (PP) but that does not cause a hypersecretion syndrome (is non-functioning) and instead presents with only non-specific symptoms such as weight loss, abdominal pain, jaundice, diarrhea and/or an abdominal mass, hence leading to a late diagnosis. PPoma can be associated with multiple endocrine neoplasia 1 (MEN-1; see this term).

3308
(4.0%)

Opsoclonus-myoclonus syndrome

Retinopathy

Opsoclonus myoclonus syndrome (OMS) is a rare neuroinflammatory disease of paraneoplastic, parainfectious or idiopathic origin, characterized by opsoclonus, myoclonus, ataxia, and behavioral and sleep disorders.

3308
(4.0%)

Eosinophilic colitis

Autism

3308
(4.0%)

Panhypophysitis

Amenorrhea

Panhypophysitis is a rare, acquired pituitary hormone deficiency, a type of primary hypophysitis characterized by an inflammation of the entire pituitary gland. Common clinical presentation is diabetes insipidus with polyuria and polydipsia and partial or panhypopituitarism. Other symptoms may include headaches, nausea/vomiting, visual disturbances and fatigue.

3308
(4.0%)

Hyperinsulinism due to short chain 3-hydroxylacyl-CoA dehydrogenase deficiency

Pigmentary retinopathy

Autosomal recessive inheritance

Hyperinsulinism due to short chain 3 hydroxylacyl-CoA dehydrogenase (SCHAD) deficiency is a recently described mitochondrial fatty acid oxidation disorder characterized by hyperinsulinemic hypoglycemia with seizures, and in one case fulminant hepatic failure.

3308
(4.0%)

Non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy

Proteinuria

3308
(4.0%)

Frontotemporal dementia with motor neuron disease

Ptosis

Frontotemporal dementia with motor neuron disease (FTD-MND) is a type of frontotemporal lobar degeneration characterized by the insidious onset (between the ages of 38-78 years) of dementia-associated psychiatric symptoms (e.g. personality changes, uninhibited behavior, irritability, aggressiveness), memory difficulties, global intellectual impairment, emotional disorders and transcortical motor aphasia that eventually leads to mutism, in addition to the manifestations of motor neuron disease such as neurogenic muscular wasting (similar to what is seen in amyotrophic lateral sclerosis; see this term). The disease is progressive, with death occurring 2-5 years after onset.

3308
(4.0%)

Spinocerebellar ataxia type 7

Retinopathy

Autosomal dominant inheritance Genetic anticipation with paternal anticipation bias

Spinocerebellar ataxia type 7 (SCA7), currently the only known form of autosomal dominant cerebellar ataxia type 2 (ADCA2; see this term), is a neurodegenerative disorder characterized by progressive ataxia, motor system abnormalities, dysarthria, dysphagia and retinal degeneration leading to progressive blindness.

3308
(4.0%)

Maternally-inherited diabetes and deafness

Renal insufficiency

Mitochondrial inheritance

Maternally inherited diabetes and deafness (MIDD) is a mitochondrial disorder characterized by maternally transmitted diabetes and sensorineural deafness.

3308
(4.0%)

Cocaine intoxication

Psychosis

3308
(4.0%)

Multiple endocrine neoplasia type 4

Abnormality of the endocrine system

Autosomal dominant inheritance

Multiple endocrine neoplasia type 4 (MEN4) is a very rare form of MEN (see this term), an inherited cancer syndrome, characterized by parathyroid and anterior pituitary tumors, possibly associated with adrenal, renal, and reproductive organ tumors.

3308
(4.0%)

Posterior cortical atrophy

Abnormality of vision

Posterior Cortical Atrophy (PCA) is a rare progressive neurodegenerative disorder with a typical onset between 50-65 years of age characterized by progressive impairment of higher visual processing skills and other posterior cortical functions without any evidence of ocular abnormalities.

3308
(4.0%)

Dermatofibrosarcoma protuberans

Aggressive behavior

Dermatofibrosarcoma protuberans (DFSP) is a rare infiltrating soft tissue sarcoma, generally of low grade malignancy, arising from the dermis of the skin and characteristically associated with a specific chromosomal translocation t(17;22).

3308
(4.0%)

Colchicine poisoning

Renal insufficiency

Colchicine poisoning is a potentially life-threatening poisoning, due to ingestion of the drug or consumption of the plant Colchicum autumnale, that usually begins with gastrointestinal symptoms (e.g. abdominal pain, nausea, vomiting, and diarrhea, that cause severe dehydration) and an initial leukocytosis leading to marrow failure (24 hours after ingestion), followed by potentially fatal multi-organ failure with mental status change, oliguric renal failure, disseminated intravascular coagulation, electrolyte imbalance, acid-base disturbance, cardiac failure/arrest and shock within 1-3 days.

3308
(4.0%)

Primary lateral sclerosis

Dementia

Primary lateral sclerosis (PLS) is an idiopathic non-familial motor neuron disease characterized by slowly progressive upper motor neuron dysfunction leading to spasticity, mild weakness in voluntary muscle movement, hyperreflexia, and loss of motor speech production.

3308
(4.0%)

MODY

Abnormality of the kidney

Autosomal dominant inheritance

MODY (maturity-onset diabetes of the young) is a rare, familial, clinically and genetically heterogeneous form of diabetes characterized by young age of onset (generally 10-45 years of age) with maintenance of endogenous insulin production, lack of pancreatic beta-cell autoimmunity, absence of obesity and insulin resistance and extra-pancreatic manifestations in some subtypes.

3308
(4.0%)

Acquired ichthyosis

Renal insufficiency

3308
(4.0%)

Fragile X-associated tremor/ataxia syndrome

Strabismus

X-linked dominant inheritance

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a rare neurodegenerative disorder characterized by adult-onset progressive intention tremor and gait ataxia.

3308
(4.0%)

Epidermodysplasia verruciformis

Blindness

Autosomal recessive inheritance

Epidermodysplasia verruciformis (EV) is a rare inherited genodermatosis characterized by chronic infection with human papillomavirus (HPV) leading to polymorphous cutaneous lesions and high risk of developing non melanoma skin cancer.

3308
(4.0%)

Fructose-1,6-bisphosphatase deficiency

Irritability

Autosomal recessive inheritance

Fructose-1,6-biphosphatase (FBP) deficiency is a disorder of fructose metabolism (see this term) characterized by recurrent episodes of fasting hypoglycemia with lactic acidosis, that may be life-threatening in neonates and infants.

3308
(4.0%)

Wells syndrome

Jaundice

Wells syndrome is characterised by the presence of recurrent cellulitis-like eruptions with eosinophilia.

3308
(4.0%)

Neuroendocrine tumor of stomach

Dermatological manifestations of systemic disorders

Gastric neuroendocrine tumor is a rare subtype of neuroendocrine neoplasm, arising from enterochromaffin-like cells in the stomach, with a variable clinical presentation, disease course and prognosis, depending on the disease type and histological grade. Most patients are asymptomatic, with diagnosis usually occurring incidentally during gastroscopy, however, symptoms of dyspepsia, anemia, pain, weight loss and gastrointestinal bleeding can be observed. Association with Zollinger-Ellison syndrome and multiple endocrine neoplasia type I has been reported.

3308
(4.0%)

Acute fatty liver of pregnancy

Polyuria

A rare, severe complication occurring in the third trimester of pregnancy or in early postpartum period bearing a risk for perinatal and maternal mortality and characterized by jaundice, rise of hepatic injuries and evolving to acute liver failure and encephalopathy.

3308
(4.0%)

Plasma cell leukemia

Renal insufficiency

3308
(4.0%)

Adenohypophysitis

Amenorrhea

A rare, acquired pituitary hormone deficiency, a type of primary hypophysitis characterized by an inflammation of anterior pituitary. Clinical presentation is variable and includes headaches, visual disturbances, symptoms of adrenal insufficiency, hyperprolactinemia, hypothyroidism and hypogonadism. It most commonly affects young women during pregnancy or postpartum period.

3308
(4.0%)

Manganese poisoning

Visual impairment

3308
(4.0%)

Niemann-Pick disease type C

Vertical supranuclear gaze palsy

Niemann-Pick disease type C (NP-C) is a lysosomal lipid storage disease (see this term) characterized by variable clinical signs, depending on the age of onset, such as prolonged unexplained neonatal jaundice or cholestasis, isolated unexplained splenomegaly, and progressive, often severe neurological symptoms such as cognitive decline, cerebellar ataxia, vertical supranuclear gaze palsy (VSPG), dysarthria, dysphagia, dystonia, seizures, gelastic cataplexy, and psychiatric disorders.

3308
(4.0%)

Lafora disease

Blindness

Autosomal recessive inheritance Heterogeneous

Lafora disease (LD) is a rare, inherited, severe, progressive myoclonic epilepsy characterized by myoclonus and/or generalized seizures, visual hallucinations (partial occipital seizures), and progressive neurological decline.

3308
(4.0%)

Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency

Retinopathy

Autosomal recessive inheritance

A mitochondrial disorder of long chain fatty acid oxidation characterized in most patients by onset in infancy/ early childhood of hypoketotic hypoglycemia, metabolic acidosis, liver disease, hypotonia and, frequently, cardiac involvement with arrhythmias and/or cardiomyopathy.

3308
(4.0%)

Beta-ketothiolase deficiency

Agitation

Autosomal recessive inheritance

A rare organic aciduria affecting ketone body metabolism and the catabolism of isoleucine and characterized by intermittent ketoacidotic episodes associated with vomiting, dyspnea, tachypnoea, hypotonia, lethargy and coma, with an onset during infancy or toddlerhood and usually ceasing by adolescence.

3308
(4.0%)

Subacute sclerosing leukoencephalitis

Nephrotic syndrome

Autosomal recessive inheritance

A chronic progressive encephalitis that develops a few years after measles infection and presents with a demyelination of the cerebral cortex.

3308
(4.0%)

Ornithine transcarbamylase deficiency

Blindness

X-linked recessive inheritance

Ornithine transcarbamylase deficiency (OTCD) is a disorder of urea cycle metabolism and ammonia detoxification (see this term) characterized by either a severe, neonatal-onset disease found almost exclusively in males, or later-onset (partial) forms of the disease. Both present with episodes of hyperammonemia that can be fatal and which can lead to neurological complications.

3308
(4.0%)

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome

Chorioretinal atrophy

Autosomal recessive inheritance

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (triple H syndrome) is a disorder of urea cycle metabolism characterized by either a neonatal-onset with manifestations of lethargy, poor feeding, vomiting and tachypnea or, more commonly, presentations in infancy, childhood or adulthood with chronic neurocognitive deficits, acute encephalopathy and/or chronic liver dysfunction.

3308
(4.0%)

Primary hepatic neuroendocrine carcinoma

Ptosis

Primary hepatic neuroendocrine carcinoma (PHNEC) is a rare hepatic tumor that may manifest with abdominal pain or fullness, as well as diarrhea or weight loss. More than 10% of cases are asymptomatic and in rare cases a carcinoid syndrome may be observed.

3308
(4.0%)

Intermediate uveitis

Proteinuria

3308
(4.0%)

Early-onset schizophrenia

Behavioral abnormality

A rare, neurologic disease characterized by an early onset of positive and negative symptoms of psychosis that impact development and cognitive functioning. Clinical manifestation commonly include premorbid features of autism spectrum disorders, attention deficits, neurodevelopmental delays, and behavioral abnormalities. After the onset of psychotic symptoms, other comorbidities are also common, including obsessive-compulsive disorder, major depressive disorder, attention deficit hyperactivity disorder, expressive and receptive language disorders, auditory processing deficits, and executive functioning deficits.

3308
(4.0%)

Mitochondrial DNA-associated Leigh syndrome

Abnormal renal tubule morphology

Maternally inherited Leigh syndrome is a rare subtype of Leigh syndrome (see this term) characterized clinically by encephalopathy, lactic acidosis, seizures, cardiomyopathy, respiratory disorders and developmental delay, with onset in infancy or early childhood, and resulting from maternally-inherited mutations in mitochondrial DNA.

3308
(4.0%)

VIPoma

Diabetes mellitus

VIPoma is an extremely rare type of pancreatic neuroendocrine tumor (see this term) that secretes vasoactive intestinal polypeptide (VIP) leading to the manifestations of watery diarrhea, hypokalemia and achlorhydia or hypochhlorhydia (known as WDHA syndrome).

3308
(4.0%)

Hypokalemic periodic paralysis

Gynecomastia

A rare disorder characterised by episodes of muscle paralysis lasting from a few to 24-48 hours and associated with a fall in blood potassium levels.