Primary adrenocortical insufficiency- MedGen UID:
- 1324
- •Concept ID:
- C0001403
- •
- Disease or Syndrome
Chronic primary adrenal insufficiency (CPAI) is a chronic disorder of the adrenal cortex resulting in the inadequate production of glucocorticoid and mineralocorticoid hormones.
Extreme obesity with alveolar hypoventilation- MedGen UID:
- 18472
- •Concept ID:
- C0031880
- •
- Disease or Syndrome
Hypoventilation syndrome in very obese persons with excessive adipose tissue around the abdomen and diaphragm is characterized by diminished to absent ventilatory chemoresponsiveness; chronic hypoxia; hypercapnia; polycythemia; and long periods of sleep during day and night (hypersomnolence). It is a condition often related to obstructive sleep apnea but can occur separately.
Desquamative interstitial pneumonia- MedGen UID:
- 65962
- •Concept ID:
- C0238378
- •
- Disease or Syndrome
Interstitial lung disease (ILD), or pneumonitis, is a heterogeneous group of disorders characterized pathologically by expansion of the interstitial compartment of the lung by inflammatory cells. Fibrosis occurs in many cases (Visscher and Myers, 2006). See also interstitial lung disease-1 (ILD1; 619611).
Desquamative interstitial pneumonitis (DIP) was originally described as a pathologic entity by Liebow et al. (1965). Lung biopsy shows diffuse and uniform filling of alveoli by clusters of cells which Liebow et al. (1965) speculated to be 'desquamated pneumocytes.' Since then, these cells have been shown primarily to be pigmented alveolar macrophages. Other features include thickened alveolar septa with an infiltrate of inflammatory cells and plump, cuboidal type II pneumocytes. Mild collagen deposition without architectural distortion or honeycombing may be present. Different forms of ILD represent pathologic classifications based on histologic patterns rather than clinical diagnoses and may occur in a variety of clinical contexts (Visscher and Myers, 2006).
Although DIP occurs most often as a sporadic disorder in adults during the third to fifth decade of life and is highly associated with smoking (Carrington et al., 1978), reports of a familial form with onset in infancy and early death suggest a genetic basis (Sharief et al., 1994).
Cases of DIP reported in infants are often more severe and refractory to treatment than those reported in adults (Nogee et al., 2001).
Deficiency of cytochrome-b5 reductase- MedGen UID:
- 75661
- •Concept ID:
- C0268193
- •
- Disease or Syndrome
Methemoglobinemia due to NADH-cytochrome b5 reductase deficiency is an autosomal recessive disorder characterized clinically by decreased oxygen carrying capacity of the blood, with resultant cyanosis and hypoxia (review by Percy and Lappin, 2008).
There are 2 types of methemoglobin reductase deficiency. In type I, the defect affects the soluble form of the enzyme, is restricted to red blood cells, and causes well-tolerated methemoglobinemia. In type II, the defect affects both the soluble and microsomal forms of the enzyme and is thus generalized, affecting red cells, leukocytes, and all body tissues. Type II methemoglobinemia is associated with mental deficiency and other neurologic symptoms. The neurologic symptoms may be related to the major role played by the cytochrome b5 system in the desaturation of fatty acids (Vives-Corrons et al., 1978; Kaplan et al., 1979).
Congenital laryngeal abductor palsy- MedGen UID:
- 96004
- •Concept ID:
- C0396059
- •
- Disease or Syndrome
Laryngeal abductor paralysis is an autosomal dominant condition characterized by variable penetrance and expressivity ranging from mild symptoms to neonatal asphyxia. (summary by Morelli et al., 1982; Manaligod and Smith, 1998).
Anti-glomerular basement membrane disease- MedGen UID:
- 140788
- •Concept ID:
- C0403529
- •
- Disease or Syndrome
Goodpasture syndrome, also known as anti-GBM disease, is a rare autoimmune disease consisting of alveolar hemorrhage and glomerulonephritis secondary to circulating antiglomerular basement membrane (anti-GBM) antibodies. Anti-GBM antibodies are directed against an antigen intrinsic to the alpha-3 chain of type IV collagen (COL4A3; 120070) that is expressed in the GBMs of the glomerular capillary loops and the basal membrane of the pulmonary alveoli. Goodpasture syndrome is suspected in patients with hemoptysis and hematuria and is confirmed by the presence of anti-GBM antibodies in renal biopsy specimens and serum. Patients with human leukocyte antigen HLA-DR15 and HLA-DR4 are susceptible to the development of Goodpasture syndrome. Reported cases of familial Goodpasture syndrome are extremely rare (summary by Angioi et al., 2017).
Breath-holding Spells- MedGen UID:
- 105400
- •Concept ID:
- C0476287
- •
- Sign or Symptom
The diagnosis of severe breath-holding spells (BHS) in childhood is based on a distinctive and stereotyped sequence of clinical events beginning with a provocation resulting in crying or emotional upset that leads to a noiseless state of expiration accompanied by color change and ultimately loss of consciousness and postural tone (Lombroso and Lerman, 1967; DiMario, 1992). Two clinical types are recognized based on the child's coloration (cyanotic or pallid) during these events. Most children experience the cyanotic type, although some experience mixed types. BHS is an involuntary, nonvolitional, reflexic, nonepileptic paroxysmal phenomenon of childhood. The episodes occur during full expiration despite its misnomer. Autonomic dysregulation has been hypothesized as an underlying mechanism that results in loss of consciousness (Hunt, 1990; DiMario and Burleson, 1993; Dimario et al., 1998).
Chiari type II malformation- MedGen UID:
- 108222
- •Concept ID:
- C0555206
- •
- Congenital Abnormality
Chiari malformation type II (CM2), also known as the Arnold-Chiari malformation, consists of elongation and descent of the inferior cerebellar vermis, cerebellar hemispheres, pons, medulla, and fourth ventricle through the foramen magnum into the spinal canal. CM2 is uniquely associated with myelomeningocele (open spina bifida; see 182940) and is found only in this population (Stevenson, 2004). It is believed to be a disorder of neuroectodermal origin (Schijman, 2004).
For a general phenotypic description of the different forms of Chiari malformations, see Chiari malformation type I (CM1; 118420).
Cardiomyopathy-hypotonia-lactic acidosis syndrome- MedGen UID:
- 324373
- •Concept ID:
- C1835845
- •
- Disease or Syndrome
Mitochondrial phosphate carrier deficiency (MPCD) is an autosomal recessive disorder characterized by onset of cardiorespiratory insufficiency soon after birth. Patients usually require intervention in the neonatal period. The disorder may result in death in infancy, although those that survive have stabilization or amelioration of symptoms with age. Most affected individuals have hypotonia, delayed motor development, and exercise intolerance, but cognitive development is normal. Laboratory studies typically show increased serum lactate, although this may not be present. Muscle biopsy shows abnormal mitochondria and lipid accumulation. There is phenotypic variability likely depending on the location of the mutation (summary by Bhoj et al., 2015).
Telangiectasia, hereditary hemorrhagic, type 2- MedGen UID:
- 324960
- •Concept ID:
- C1838163
- •
- Disease or Syndrome
Hereditary hemorrhagic telangiectasia (HHT) is characterized by the presence of multiple arteriovenous malformations (AVMs) that lack intervening capillaries and result in direct connections between arteries and veins. The most common clinical manifestation is spontaneous and recurrent nosebleeds (epistaxis) beginning on average at age 12 years. Telangiectases (small AVMs) are characteristically found on the lips, tongue, buccal and gastrointestinal (GI) mucosa, face, and fingers. The appearance of telangiectases is generally later than epistaxis but may be during childhood. Large AVMs occur most often in the lungs, liver, or brain; complications from bleeding or shunting may be sudden and catastrophic. A minority of individuals with HHT have GI bleeding, which is rarely seen before age 50 years.
Mitochondrial complex I deficiency- MedGen UID:
- 374101
- •Concept ID:
- C1838979
- •
- Disease or Syndrome
Isolated complex I deficiency is a rare inborn error of metabolism due to mutations in nuclear or mitochondrial genes encoding subunits or assembly factors of the human mitochondrial complex I (NADH: ubiquinone oxidoreductase) and is characterized by a wide range of manifestations including marked and often fatal lactic acidosis, cardiomyopathy, leukoencephalopathy, pure myopathy and hepatopathy with tubulopathy. Among the numerous clinical phenotypes observed are Leigh syndrome, Leber hereditary optic neuropathy and MELAS syndrome (see these terms).
METHEMOGLOBINEMIA, BETA TYPE- MedGen UID:
- 333645
- •Concept ID:
- C1840779
- •
- Disease or Syndrome
Methemoglobinemia is a clinical condition in which more than 1% of hemoglobin is oxidized to methemoglobin, a type of hemoglobin that contains the ferric (Fe3+) form of iron. Patients with hemoglobin M are cyanotic but otherwise asymptomatic. If the mutation occurs in the hemoglobin alpha subunit (141800), cyanosis is apparent at birth, whereas if the beta chain is affected, cyanosis appears later or intensifies when beta subunit production increases. If a newborn carries a fetal M hemoglobin (gamma subunit; 142250), cyanosis disappears when the complete gamma-beta-switch occurs (summary by Mansouri and Lurie, 1993).
Seizures, benign familial infantile, 3- MedGen UID:
- 375105
- •Concept ID:
- C1843140
- •
- Disease or Syndrome
Benign familial neonatal-infantile seizures is an autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae (Shevell et al., 1986).
For a general phenotypic description and a discussion of genetic heterogeneity of benign familial infantile seizures, see BFIS1 (601764).
Heterotaxy, visceral, 1, X-linked- MedGen UID:
- 336609
- •Concept ID:
- C1844020
- •
- Disease or Syndrome
Heterotaxy
Heterotaxy ('heter' meaning 'other' and 'taxy' meaning 'arrangement'), or situs ambiguus, is a developmental condition characterized by randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another (Srivastava, 1997). Heterotaxy is a clinically and genetically heterogeneous disorder.
Multiple Types of Congenital Heart Defects
Congenital heart defects (CHTD) are among the most common congenital defects, occurring with an incidence of 8/1,000 live births. The etiology of CHTD is complex, with contributions from environmental exposure, chromosomal abnormalities, and gene defects. Some patients with CHTD also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions (summary by van de Meerakker et al., 2011).
Reviews
Obler et al. (2008) reviewed published cases of double-outlet right ventricle and discussed etiology and associations.
Genetic Heterogeneity of Visceral Heterotaxy
See also HTX2 (605376), caused by mutation in the CFC1 gene (605194) on chromosome 2q21; HTX3 (606325), which maps to chromosome 6q21; HTX4 (613751), caused by mutation in the ACVR2B gene (602730) on chromosome 3p22; HTX5 (270100), caused by mutation in the NODAL gene (601265) on chromosome 10q22; HTX6 (614779), caused by mutation in the CCDC11 gene (614759) on chromosome 18q21; HTX7 (616749), caused by mutation in the MMP21 gene (608416) on chromosome 10q26; HTX8 (617205), caused by mutation in the PKD1L1 gene (609721) on chromosome 7p12; HTX9 (618948), caused by mutation in the MNS1 gene (610766) on chromosome 15q21; HTX10 (619607), caused by mutation in the CFAP52 gene (609804) on chromosome 17p13; HTX11 (619608), caused by mutation in the CFAP45 gene (605152) on chromosome 1q23; and HTX12 (619702), caused by mutation in the CIROP gene (619703) on chromosome 14q11.
Genetic Heterogeneity of Multiple Types of Congenital Heart Defects
An X-linked form of CHTD, CHTD1, is caused by mutation in the ZIC3 gene on chromosome Xq26. CHTD2 (614980) is caused by mutation in the TAB2 gene (605101) on chromosome 6q25. A form of nonsyndromic congenital heart defects associated with cardiac rhythm and conduction disturbances (CHTD3; 614954) has been mapped to chromosome 9q31. CHTD4 (615779) is caused by mutation in the NR2F2 gene (107773) on chromosome 15q26. CHTD5 (617912) is caused by mutation in the GATA5 gene (611496) on chromosome 20q13. CHTD6 (613854) is caused by mutation in the GDF1 gene (602880) on chromosome 19p13. CHTD7 (618780) is caused by mutation in the FLT4 gene (136352) on chromosome 5q35. CHTD8 (619657) is caused by mutation in the SMAD2 gene (601366) on chromosome 18q21. CHTD9 (620294) is caused by mutation in the PLXND1 gene (604282) on chromosome 3q22.
Lethal congenital glycogen storage disease of heart- MedGen UID:
- 337919
- •Concept ID:
- C1849813
- •
- Disease or Syndrome
A rare glycogen storage disease with fetal or neonatal onset of severe cardiomyopathy with non-lysosomal glycogen accumulation and fatal outcome in infancy. Patients present with massive cardiomegaly, severe cardiac and respiratory complications and failure to thrive. Non-specific facial dysmorphism, bilateral cataracts, macroglossia, hydrocephalus, enlarged kidneys and skeletal muscle involvement have been reported in some cases.
Hereditary hemorrhagic telangiectasia type 4- MedGen UID:
- 341824
- •Concept ID:
- C1857688
- •
- Disease or Syndrome
Hereditary hemorrhagic telangiectasia (HHT) is characterized by the presence of multiple arteriovenous malformations (AVMs) that lack intervening capillaries and result in direct connections between arteries and veins. The most common clinical manifestation is spontaneous and recurrent nosebleeds (epistaxis) beginning on average at age 12 years. Telangiectases (small AVMs) are characteristically found on the lips, tongue, buccal and gastrointestinal (GI) mucosa, face, and fingers. The appearance of telangiectases is generally later than epistaxis but may be during childhood. Large AVMs occur most often in the lungs, liver, or brain; complications from bleeding or shunting may be sudden and catastrophic. A minority of individuals with HHT have GI bleeding, which is rarely seen before age 50 years.
Cleft larynx, posterior- MedGen UID:
- 349091
- •Concept ID:
- C1859083
- •
- Disease or Syndrome
Venular insufficiency, systemic- MedGen UID:
- 348623
- •Concept ID:
- C1860465
- •
- Disease or Syndrome
Sulfhemoglobinemia, congenital- MedGen UID:
- 350024
- •Concept ID:
- C1861437
- •
- Congenital Abnormality
Surfactant metabolism dysfunction, pulmonary, 1- MedGen UID:
- 368844
- •Concept ID:
- C1968602
- •
- Disease or Syndrome
Inborn errors of pulmonary surfactant metabolism are genetically heterogeneous disorders resulting in severe respiratory insufficiency or failure in full-term neonates or infants. These disorders are associated with various pathologic entities, including pulmonary alveolar proteinosis (PAP), desquamative interstitial pneumonitis (DIP), or cellular nonspecific interstitial pneumonitis (NSIP) (Clark and Clark, 2005).
A clinically similar disorder characterized by respiratory distress (267450) can affect preterm infants, who show developmental deficiency of surfactant.
Acquired PAP (610910) is an autoimmune disorder characterized by the presence of autoantibodies to CSF2 (138960).
Genetic Heterogeneity of Pulmonary Surfactant Metabolism Dysfunction
See also SMDP2 (610913), caused by mutation in the SPTPC gene (178620) on 8p21; SMDP3 (610921), caused by mutation in the ABCA3 gene (601615) on 16p13; SMDP4 (300770), caused by mutation in the CSF2RA gene (306250) on Xp22; and SMDP5 (614370), caused by mutation in the CSF2RB gene (138981) on 22q12.
Interstitial lung disease due to ABCA3 deficiency- MedGen UID:
- 410074
- •Concept ID:
- C1970456
- •
- Disease or Syndrome
For a general phenotypic description and a discussion of genetic heterogeneity of pulmonary surfactant metabolism dysfunction, see SMDP1 (265120).
Surfactant metabolism dysfunction, pulmonary, 2- MedGen UID:
- 410078
- •Concept ID:
- C1970470
- •
- Disease or Syndrome
Pulmonary surfactant metabolism dysfunction-2 (SMDP2) is a rare autosomal dominant disease associated with progressive respiratory insufficiency and lung disease with a variable clinical course. The pathophysiology of the disorder is postulated to involve intracellular accumulation of a structurally defective SPC protein (Thomas et al., 2002).
For a general phenotypic description and a discussion of genetic heterogeneity of pulmonary surfactant metabolism dysfunction, see SMDP1 (265120).
Autoimmune pulmonary alveolar proteinosis- MedGen UID:
- 410079
- •Concept ID:
- C1970472
- •
- Disease or Syndrome
Pulmonary alveolar proteinosis is a pathologic entity characterized by intraalveolar surfactant accumulation. There are 3 clinically distinct forms: hereditary (usually congenital), secondary, and acquired. The acquired form of pulmonary alveolar proteinosis is the most common form, accounting for approximately 90% of cases. The mean age at diagnosis is 39 years and it is associated with smoking in 72% of cases. The estimated incidence and prevalence are 0.36 and 3.70 cases per million, respectively (Trapnell et al., 2003; Seymour and Presneill, 2002).
Secondary pulmonary alveolar proteinosis develops in association with conditions involving functional impairment or reduced numbers of alveolar macrophages. Such conditions include some hematologic cancers, pharmacologic immunosuppression, inhalation of inorganic dust or toxic fumes, and certain infections. Congenital pulmonary alveolar proteinosis is a rare, severe, often fatal disorder of newborns associated with pulmonary surfactant metabolism dysfunction caused by mutations in genes involved in surfactant metabolism (see, e.g., SMDP1, 265120) (Trapnell et al., 2003).
See 300770 for information on congenital PAP due to CSF2RA (306250) deficiency.
Cyanosis, transient neonatal- MedGen UID:
- 462771
- •Concept ID:
- C3151421
- •
- Disease or Syndrome
Neonatal cyanosis is characterized by symptoms in the fetus and neonate that gradually abate by 5 to 6 months of age. The disorder is caused by a defect in the fetal hemoglobin chain, which causes reduced affinity for oxygen due to steric inhibition of oxygen binding and/or due to increased oxidation of the fetal hemoglobin molecule to methemoglobin (Hb FM), which has decreased oxygen-binding capacity. Some patients develop anemia resulting from increased destruction of red cells containing abnormal or unstable hemoglobin. The cyanosis resolves spontaneously by 5 to 6 months of age or earlier, as the adult beta-globin chain (HBB; 141900) is produced and replaces the fetal gamma-globin chain (summary by Crowley et al., 2011).
Heterotaxy, visceral, 7, autosomal- MedGen UID:
- 902629
- •Concept ID:
- C4225217
- •
- Disease or Syndrome
Autosomal visceral heterotaxy-7 is an autosomal recessive developmental disorder characterized by complex congenital heart malformations and/or situs inversus and caused by defects in the normal left-right asymmetric positioning of internal organs. The phenotype is variable (summary by Guimier et al., 2015).
For a discussion of the genetic heterogeneity of visceral heterotaxy, see HTX1 (306955).
Methemoglobinemia type 4- MedGen UID:
- 925090
- •Concept ID:
- C4285231
- •
- Disease or Syndrome
Methemoglobinemia and ambiguous genitalia (METAG) is due to isolated 17,20-lyase deficiency, defined by apparently normal 17-alpha-hydroxylase activity but severely reduced 17,20-lyase activity of the CYP17A1 enzyme (609300), which results in sex steroid deficiency but normal glucocorticoid and mineralocorticoid reserve. The clinical phenotype is characterized by male undermasculinization, with absent or disturbed pubertal development in both 46,XY and 46,XX individuals. Mild to severe methemoglobinemia has been reported in these patients (Idkowiak et al., 2012).
Other autosomal recessive methemoglobinemias include types I and II (see 250800), caused by mutation in the CYB5R3 gene (613213). Isolated 17,20-lyase deficiency can also be caused by mutation in the CYP17A1 gene (609300), and mutation in the POR gene can manifest clinically as isolated 17,20-lyase deficiency (see 124015.0016).
Congenital myasthenic syndrome 21- MedGen UID:
- 934621
- •Concept ID:
- C4310654
- •
- Disease or Syndrome
Any congenital myasthenic syndrome in which the cause of the disease is a mutation in the SLC18A3 gene.
PERCHING syndrome- MedGen UID:
- 934709
- •Concept ID:
- C4310742
- •
- Disease or Syndrome
PERCHING syndrome is an autosomal recessive multisystem disorder characterized by global developmental delay, dysmorphic facial features, feeding and respiratory difficulties with poor overall growth, axial hypotonia, and joint contractures. The features are variable, even within families, and may also include retinitis pigmentosa, cardiac or genitourinary anomalies, and abnormal sweating. Each letter of the PERCHING acronym represents 2 important phenotypic elements: Postural and Palatal abnormalities; Exophthalmos and Enteral-tube dependency/feeding issues; Respiratory distress and Retinitis pigmentosa; Contractures and Camptodactyly; Hypertelorism and Hirsutism; Intrauterine growth retardation (IUGR)/growth failure and Intellectual disability/developmental delay; Nevus flammeus and Neurologic malformations; and facial Gestalt/grimacing and Genitourinary abnormalities (Jeffries et al., 2019). Death in infancy or early childhood often occurs, although survival to the third decade has been reported. Some of the features, such as contractures, dysmorphic craniofacial features, and severe feeding difficulties, are reminiscent of Bohring-Opitz syndrome (605039) (summary by Kanthi et al., 2019 and Buers et al., 2020).
Structural heart defects and renal anomalies syndrome- MedGen UID:
- 1387412
- •Concept ID:
- C4479549
- •
- Disease or Syndrome
Benign familial neonatal-infantile seizures 1- MedGen UID:
- 1638448
- •Concept ID:
- C4551769
- •
- Disease or Syndrome
Benign familial infantile seizures (BFIS) is a seizure disorder of early childhood with age at onset from 3 months up to 24 months. It is characterized by brief seizures beginning with slow deviation of the head and eyes to 1 side and progressing to generalized motor arrest and hypotonia, apnea and cyanosis, and limb jerks. Seizures usually occur in clusters over a day or several days. The ictal EEG shows focal parietal-temporal activity, whereas the interictal EEG is normal. Concurrent and subsequent psychomotor and neurologic development are normal (Franzoni et al., 2005).
See also benign familial neonatal seizures (BFNS1; 121200).
Deprez et al. (2009) provided a review of the genetics of epilepsy syndromes starting in the first year of life, and included a diagnostic algorithm.
Genetic Heterogeneity of Benign Familial Infantile Seizures
The BFIS1 locus has been mapped to chromosome 19q. BFIS2 (605751) is caused by mutation in the PRRT2 gene on chromosome 16p11. BFIS3 (607745), which is caused by the mutations in the SCN2A gene (182390) on chromosome 2q24, has a slightly earlier age at onset and is sometimes termed benign familial 'neonatal-infantile' seizures. BFIS4 (612627) has been mapped to chromosome 1p. BFIS5 (617080) is caused by mutation in the SCN8A gene (600702) on chromosome 12q13. BFIS6 (see 610353) is caused by mutation in the CHRNA2 gene (118502) on chromosome 8p21.
Telangiectasia, hereditary hemorrhagic, type 1- MedGen UID:
- 1643786
- •Concept ID:
- C4551861
- •
- Disease or Syndrome
Hereditary hemorrhagic telangiectasia (HHT) is characterized by the presence of multiple arteriovenous malformations (AVMs) that lack intervening capillaries and result in direct connections between arteries and veins. The most common clinical manifestation is spontaneous and recurrent nosebleeds (epistaxis) beginning on average at age 12 years. Telangiectases (small AVMs) are characteristically found on the lips, tongue, buccal and gastrointestinal (GI) mucosa, face, and fingers. The appearance of telangiectases is generally later than epistaxis but may be during childhood. Large AVMs occur most often in the lungs, liver, or brain; complications from bleeding or shunting may be sudden and catastrophic. A minority of individuals with HHT have GI bleeding, which is rarely seen before age 50 years.
Methemoglobinemia, alpha type- MedGen UID:
- 1635511
- •Concept ID:
- C4693798
- •
- Disease or Syndrome
Methemoglobinemia is a clinical condition in which more than 1% of hemoglobin is oxidized to methemoglobin, a type of hemoglobin that contains the ferric (Fe3+) form of iron. Patients with hemoglobin M are cyanotic but otherwise asymptomatic. If the mutation occurs in the hemoglobin alpha subunit, cyanosis is apparent at birth, whereas if the beta chain (141900) is affected, cyanosis appears later or intensifies when beta subunit production increases. If a newborn carries a fetal M hemoglobin (gamma subunit; 142250), cyanosis disappears when the complete gamma-beta-switch occurs (summary by Mansouri and Lurie, 1993).
Encephalopathy, acute, infection-induced, susceptibility to, 9- MedGen UID:
- 1673394
- •Concept ID:
- C5193089
- •
- Finding
Susceptibility to acute infection-induced encephalopathy-9 (IIAE9) is an autosomal recessive disorder characterized by episodic acute neurodegeneration and developmental regression associated with infections and febrile illness. Patients present in the first months or years of life, often after normal or only mildly delayed early development. Some patients may have partial recovery between episodes, such as transient ataxia, but the overall disease course is progressive, resulting in global developmental delay, abnormal movements, refractory seizures, microcephaly, and cerebellar atrophy (summary by Fichtman et al., 2019).
For a discussion of genetic heterogeneity of susceptibility to acute infection-induced encephalopathy, see 610551.
Neurodevelopmental disorder with impaired language and ataxia and with or without seizures- MedGen UID:
- 1794216
- •Concept ID:
- C5562006
- •
- Disease or Syndrome
Neurodevelopmental disorder with impaired language and ataxia and with or without seizures (NEDLAS) is characterized by axial hypotonia and global developmental delay apparent in early infancy. Affected individuals have delayed walking with gait ataxia and poor language development. Behavioral abnormalities also commonly occur. The severity is highly variable: a subset of patients have a more severe phenotype with early-onset seizures resembling epileptic encephalopathy, inability to walk or speak, and hypomyelination on brain imaging (summary by Stolz et al., 2021).
Phosphoenolpyruvate carboxykinase deficiency, cytosolic- MedGen UID:
- 1801754
- •Concept ID:
- C5574905
- •
- Disease or Syndrome
Cytosolic phosphoenolpyruvate carboxykinase deficiency causes a defect in gluconeogenesis that results in a 'biochemical signature' of fasting hypoglycemia with high tricarboxylic acid cycle intermediate excretion, particularly of fumarate. Other biochemical anomalies that may be seen during metabolic crisis include ketonuria, dicarboxylic aciduria, and urea cycle dysfunction (Vieira et al., 2017).
See PCKDM (261650) for a discussion of mitochondrial PCK (PEPCK2; 614095) deficiency.
Restrictive dermopathy 2- MedGen UID:
- 1801155
- •Concept ID:
- C5676942
- •
- Disease or Syndrome
Restrictive dermopathy is a rare genodermatosis characterized mainly by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial dysmorphism (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures, and an early neonatal lethal course. Liveborn children usually die within the first week of life (summary by Navarro et al., 2004).
For a discussion of genetic heterogeneity of restrictive dermopathy, see RSDM1 (275210).
Meckel syndrome 14- MedGen UID:
- 1809650
- •Concept ID:
- C5676989
- •
- Disease or Syndrome
Meckel syndrome-14 (MKS14) is a lethal disorder characterized by occipital encephalocele, postaxial polydactyly of the hands and feet, and polycystic kidneys. Stillbirth has been reported, as well as death within hours in a live-born affected individual (Shaheen et al., 2016; Ridnoi et al., 2019).
For a general phenotypic description and discussion of genetic heterogeneity of Meckel syndrome, see MKS1 (249000).
Cardiac valvular defect, developmental- MedGen UID:
- 1823949
- •Concept ID:
- C5774175
- •
- Disease or Syndrome
Cardiac valvular dysplasia-1 (CVDP1) is characterized by congenital malformations of the pulmonic, tricuspid, and mitral valves. Structural cardiac defects, including atrial and ventricular septal defects, single left ventricle, and hypoplastic right ventricle have also been observed in affected individuals (Ta-Shma et al., 2017).
Genetic Heterogeneity of Cardiac Valvular Dysplasia
CVDP2 (620067) is caused by mutation in the ADAMTS19 gene (607513) on chromosome 5q23.
Multiple mitochondrial dysfunctions syndrome 7- MedGen UID:
- 1841222
- •Concept ID:
- C5830586
- •
- Disease or Syndrome
Mitochondrial dysfunctions syndrome-7 (MMDS7) is an autosomal recessive disorder characterized by a clinical spectrum ranging from neonatal fatal glycine encephalopathy to an attenuated phenotype of developmental delay, behavioral problems, limited epilepsy, and variable movement problems (Arribas-Carreira et al., 2023).
For a general description and a discussion of genetic heterogeneity of multiple mitochondrial dysfunctions syndrome, see MMDS1 (605711).
Pulmonary hypertension, primary, 6- MedGen UID:
- 1863339
- •Concept ID:
- C5935600
- •
- Disease or Syndrome
Primary pulmonary hypertension-6 (PPH6) is characterized by markedly elevated pulmonary arterial hypertension, associated with reduced oxygen saturation and diffuse ground-glass opacities on chest x-ray. Lung biopsy shows thickening of the alveolar septae and abnormally proliferating capillaries (Postma et al., 2023).
For a general phenotypic description and a discussion of genetic heterogeneity of primary pulmonary hypertension, see PPH1 (178600).