eRAM

The multiple symptoms of SIOD and the relative frequency of them are listed in the table. The symptoms are subsequently discussed in according to the organ system affected.Physical TraitsMost affected individuals have distinctive physical features. These include fine hair (60%), a thin upper lip, a broad, low nasal bridge (68%), a bulbous nasal tip (83%), and disproportionately short stature (98%). Additional features include excessive inward curvature of the lumbar spine (lumbar lordosis, 84%), a protruding abdomen, and hyperpigmented macules (85%) on the trunk and occasionally on the neck, face, arms and legs. Less common physical features include absent or small teeth and corneal opacities (19%).Growth and Skeletal SystemGrowth failure, which is often the first obvious sign of SIOD, occurs despite normal growth hormone production and is not corrected with growth hormone supplementation. In most affected individuals, the growth failure begins prior to and continues after birth; however, some affected individuals do have normal birth lengths and weights and their growth failure is not noted until after birth (range: 0 to 13 years, mean: 2 years). The heights of those who survived to adulthood were 136-157 cm for men and 98.5-143 cm for women.The short stature arises generally because of spondyloepiphyseal dysplasia (86%), a disorder of skeletal growth; it does not arise as a complication of their renal failure. The anthropometric characteristics of patients with SIOD differed markedly from those of patients with other forms of chronic kidney disease, especially with respect to median leg length and sitting height. The spinal column and hip joint are most severely affected. The radiological abnormalities include ovoid or mildly flattened vertebral bodies, small and laterally displaced femurs (thigh bone), and shallow abnormal acetabular fossae (hip sockets). Less frequent skeletal problems include lordosis, kyphosis and scoliosis (abnormal curvatures of the spine) as well as osteopenia (decreased bone mineral density) and degenerative hip disease. Many patients have required hip replacements.Endocrine SystemApproximately 42% of individuals with SIOD have reduced thyroid function. However, to date, the poor thyroid function has not caused clinical symptoms (subclinical hypothyroidism). Among those who have received thyroid hormone supplementation, the correction of thyroid hormone levels does not mitigate other symptoms of SIOD.Renal SystemAll reported affected individuals have eventually developed renal dysfunction. The kidney disease is characterized by progressively worsening loss of protein in the urine and ultimately concludes with renal failure. The progressive renal disease is not responsive to immunosuppressant therapy. The diagnosis of renal dysfunction is usually made concurrent with or within the five years following the diagnosis of the growth failure. Renal failure requiring dialysis or kidney transplantation usually develops within the subsequent 11 years, although the rate of progression varies greatly. Because renal disease causes high blood pressure and high levels of blood cholesterol and lipids, we postulate that it accentuates the vascular disease of SIOD; however, renal transplantation does not prevent progression of the atherosclerosis.Cardiovascular systemHalf of SIOD individuals develop clinical signs of atherosclerosis. The onset is often in early childhood and relentlessly progressive. The disease is not abrogated by renal or bone marrow transplantation nor by cholesterol lowering agents, although the cholesterol lowering agents and renal transplantation can slow the progression by mitigating factors such as high blood pressure and high blood lipid and cholesterol levels. Consistent with the atherosclerosis resulting from an intrinsic defect of SIOD tissue, the vascular disease does not recur in the transplanted kidneys. Besides atherosclerosis, splitting and fraying of the arterial internal elastic layer and thickening of the muscular layer of the arterial walls have been found on autopsy. The latter finding may be a complication of high blood pressure or an intrinsic defect in the blood vessels. A few patients have also developed subaortic stenosis and one patient had extensive fatty infiltration resembling that of arrhythmogenic right ventricular cardiomyopathy.Central nervous system (CNS)The central nervous system shows both mutiple developmental and ischemic changes. The developmental defects include brain malformations suggestive of aberrant neuronal migration including heterotopia, irregular cortical thickness, incomplete gyral formation, poor definition of cortical layers, and hamartia. Additionally adolescent and adult patients have very few neural progenitors (stem cells). Despite these malformations, most SIOD patients have normal social, language, motor, and cognitive development until the onset of symptoms from reduced brain blood supply (cerebral ischemia).The cerebral ischemia can either temporarily or permanently disturb the blood supply of a given area of the brain and thereby cause temporary (47%, transient ischemic attacks) or permanent (44%, strokes) dysfunction. The cerebral ischemic attacks and strokes are often precipitated by acute changes in blood pressure, such as following the administration of high doses of steroids. Ischemic changes include loss of neurons and myelin, gliosis (scarring), brain atrophy, and degeneration of infarcted regions including atrophy of the cerebellum. Likely as a complication of the cerebral ischemia and atherosclerosis, a few of the patients have also manifest moyamoya phenomenon.Another common neurological feature in SIOD patients is severe migraine-like headaches (60%). The cause of the headaches is still unknown but they tend to be more severe and refractory to anti-migraine medications that migraine-like headaches in the general population.Pulmonary systemSeveral patients have died from pulmonary complications including pulmonary emboli, pulmonary hypertension, and lung disease. Lung abnormalities identified by autopsy include diffuse thickening (hyperplasia) of the airway (bronchial) smooth muscles, enlargement (emphysematous changes) of the gas exchange regions (alveoli), and diffuse hyperplasia of the pulmonary artery smooth muscles. The last finding could account for the pulmonary hypertension observed in some patients.Hematopoietic and Immune SystemsNearly all affected individuals have some blood cell deficiency. Deficiency of T lymphocytes, a subgroup of white blood cells that plays an important role in immunity, is most common (97%). However, in addition to a deficit of T lymphocytes, the hematopoietic disturbance can include any or all other blood cell lineages.Because of their immunodeficiency, affected individuals have an increased risk for opportunistic fungal, viral and bacterial infections. They also have an increased risk of more severe infections.Reproductive systemFew SIOD patients have reached sexual maturity and of the ones who have, no children were subsequently born. However, the patients who have survived to adulthood did develop with secondary sexual characteristics and the women have menstrual cycles. The autopsy of two affected males revealed that sperm production was affected in a varying degree. In one patient, the testes showed interstitial fibrosis and absence of sperm (azoospermia), whereas the other had less interstitial fibrosis individual and produced some sperm. - NORD
Reference: NORD

immunoosseous dysplasia schimke type
immunoosseous dysplasia, schimke type
schimke immunoosseous dysplasia
siod

C0877024

C0033687  |  proteinuria  |  1
C0022658  |  renal disease  |  1
C0024314  |  lymphoproliferative disorders  |  1
C0038015  |  spondyloepiphyseal dysplasia  |  1
C0205698  |  undifferentiated carcinoma  |  1
C0024314  |  lymphoproliferative disorder  |  1
C0040188  |  tic disorders  |  1
C0022661  |  end stage renal disease  |  1

50485  |  SMARCAL1  |  CLINVAR;CTD_human;ORPHANET;UNIPROT

265  |  AMELX  |  2.078  |  DISEASES
460  |  ASTN1  |  3.848  |  DISEASES
546  |  ATRX  |  1.626  |  DISEASES
11177  |  BAZ1A  |  3.92  |  DISEASES
1876  |  E2F6  |  3.005  |  DISEASES
2335  |  FN1  |  1.535  |  DISEASES
2760  |  GM2A  |  2.936  |  DISEASES
5888  |  RAD51  |  2.169  |  DISEASES
84268  |  RPAIN  |  2.576  |  DISEASES
6594  |  SMARCA1  |  3.065  |  DISEASES
6597  |  SMARCA4  |  5.215  |  DISEASES
50485  |  SMARCAL1  |  8.157  |  DISEASES

SMARCAL1  |  2q35

HP:0000938  |  Decreased bone mineral density
HP:0000470  |  Short neck
HP:0003300  |  Oval vertebral bodies
HP:0000691  |  Decreased width of tooth
HP:0001888  |  Lymphocytopenia
HP:0003521  |  Disproportionate short-trunk short stature
HP:0000097  |  focal glomerulosclerosis
HP:0005930  |  Abnormality of epiphysis morphology
HP:0007759  |  Cloudy cornea
HP:0010701  |  Abnormal serum level of immunoglobulin
HP:0005280  |  Depressed nasal bridge
HP:0000093  |  Proteinuria
HP:0000470  |  Decreased cervical height
HP:0000083  |  Renal insufficiency
HP:0001034  |  Hyperpigmented spots
HP:0100820  |  Glomerulopathy
HP:0002326  |  TIA
HP:0001873  |  Thrombocytopenia
HP:0005374  |  Cellular immunodeficiency
HP:0002938  |  Exaggerated lumbar lordosis
HP:0003307  |  Hyperlordosis
HP:0002719  |  infections, recurrent
HP:0000822  |  Hypertension
HP:0001888  |  Lymphopenia
HP:0002925  |  Increased serum thyroid-stimulating hormone
HP:0000100  |  Nephrosis
HP:0001511  |  Intrauterine growth retardation
HP:0002843  |  Cellular immune defect
HP:0002843  |  Abnormality of T cells
HP:0006453  |  Laterally displaced femoral heads
HP:0001538  |  Protuberant abdomen
HP:0001903  |  Anemia
HP:0001270  |  Motor retardation
HP:0003182  |  Shallow acetabulae
HP:0002213  |  Thin hair shaft
HP:0003312  |  Abnormal form of the vertebral bodies
HP:0002942  |  Thoracic kyphosis
HP:0000545  |  Near sightedness
HP:0005280  |  Flat, nasal bridge
HP:0000483  |  Astigmatism
HP:0001875  |  Neutropenia
HP:0000926  |  Platyspondyly
HP:0001873  |  Low platelet count
HP:0001511  |  Prenatal onset growth retardation
HP:0000926  |  Flattened vertebral bodies
HP:0000995  |  Melanocytic nevus
HP:0002515  |  Waddling gait
HP:0002208  |  Coarse hair texture
HP:0000691  |  Microdontia
HP:0003300  |  Ovoid vertebral bodies
HP:0002634  |  Arteriosclerosis
HP:0003090  |  Hypoplasia of the capital femoral epiphysis
HP:0000100  |  Nephrotic syndrome
HP:0002827  |  Hip dislocation
HP:0001620  |  High pitched voice
HP:0007565  |  Multiple cafe-au-lait spots
HP:0000414  |  Bulbous nose
HP:0002655  |  Spondyloepiphyseal dysplasia

HP:0012408  |  Medullary nephrocalcinosis  |  1
HP:0000093  |  Proteinuria  |  1
HP:0002656  |  Epiphyseal dysplasia  |  1
HP:0002655  |  Spondyloepiphyseal dysplasia  |  1
HP:0030731  |  Carcinoma  |  1
HP:0002960  |  Autoimmune condition  |  1
HP:0003774  |  End-stage renal failure  |  1
HP:0005607  |  Tracheobronchial anomalies  |  1
HP:0005523  |  Lymphoproliferative disorder  |  1
HP:0000164  |  Abnormality of the teeth  |  1
HP:0100033  |  Tic disorder  |  1