Ochoa (urofacial) syndrome, also known as hydronephrosis with peculiar facial expression, is an extremely rare inherited disorder characterized by an abnormal facial expression and obstructive disease of the urinary tract (uropathy) that are present at birth (congenital). When affected infants smile, their facial musculature turns upside down or "inverts" so that they appear to be grimacing or crying. The urinary abnormality is an obstructive uropathy in which failure of nerve signals between the bladder and the spinal cord results in incomplete emptying of the bladder (neurogenic or neuropathic bladder). In addition, neurogenic bladder may result in involuntary discharge of urine (enuresis), urinary tract infections, and/or abnormal accumulation of urine in the kidneys (hydronephrosis). Additional abnormalities may include inflammation of the kidneys and pelvis (pyelonephritis), backflow of urine into the tubes that carry urine from the kidney to the bladder (vesicoureteral reflex), and/or involuntary spasms of the ring of muscle around the anus (external sphincter). In some cases, affected individuals may develop renal failure during adolescence or the early 20s, potentially leading to life-threatening complications.
Ochoa syndrome occurs due to disruption or changes (mutations) of a gene on the long arm (q) of chromosome 10 (10q23-q24). Ochoa syndrome has been identified as an autosomal recessive trait.
Ochoa syndrome is a rare inherited disorder also known as urofacial syndrome. As the term “urofacial” suggests, the disorder is characterized by urinary and facial abnormalities. The initial finding that may be apparent in affected infants is an unusual “inverted” facial expression. When affected infants attempt to laugh or smile, their facial musculature “inverts” so that they appear to be grimacing or crying.
The urinary abnormality associated with Ochoa syndrome is an obstructive disease of the urinary tract that is present at birth (congenital obstructive uropathy). This uropathy occurs due to failure of nerve signals between the bladder and spinal cord causing incomplete emptying of the bladder (neurogenic or neuropathic bladder). At the lowest point of the bladder, there is a circular band of muscle fibers (urethral sphincter) that opens into the urethra, the tubular structure through which urine is excreted. When the bladder fills with urine, signals are normally sent to the spinal cord. Nerve signals are then sent back that cause the urethral sphincter to relax. The bladder then contracts and sends urine through the urethra. However, in affected infants, there is a failure of such nerve signalling for unknown reasons, resulting in improper, incomplete emptying of the bladder (mild occult neurogenic bladder).
In most cases, neurogenic bladder may lead to the backflow (reflux) of urine into the tubes that normally bring urine to the bladder (ureters) from the kidneys; an abnormal swelling (distention) of and accumulation of urine in the ureters (hydroureter) and kidneys (hydronephrosis); and/or ureter blockage (obstruction). In affected individuals, hydroureter and hydronephrosis may range from mild to severe. An early symptom of such abnormalities may include an inability to hold urine during the day and/or at night during sleep (diurnal and noctural enuresis). In addition, affected individuals may experience inflammation of the kidneys and pelvis (pyelonephritis) and/or involuntary spasms of the ring of muscle around the anus (external sphincter).
Obstructive abnormalities of the urinary tract may result in urinary tract damage and repeated urinary tract infections. In some cases, such infections may cause no symptoms (asymptomatic). However, in other cases, a variety of symptoms may occur such as a frequent urge to urinate, a burning sensation when passing urine, a general feeling of ill health (malaise), fever, pain in the lower abdomen and/or loins, and/or, in severe infections, the presence of blood (hematuria) and/or pus in the urine. Without appropriate treatment, repeated urinary tract infections may lead to chronic renal failure. Renal failure occurs when the kidneys lose their ability to excrete waste products through the urine, to regulate the balance of salt and water in the body, and to perform their other vital functions.
Many individuals with Ochoa syndrome may also have additional physical abnormalities. Approximately two thirds of affected individuals may experience infrequent or incomplete passing of stools (constipation). In all reported males with the disorder, the testicles have failed to descend into the scrotum (cryptorchidism). Some individuals with the disorder may also have high blood pressure (hypertension) and/or experience abnormally slow growth.
Ochoa syndrome has been identified as an autosomal recessive genetic trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes (i.e., alleles, one of two genes at the same location on a matched chromosome). One gene is received from the father and one from the mother.
In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy. As an autosomal recessive disorder, the offspring of parents who are closely related by blood (consanguineous) have a much higher chance of inheriting two defective genes.
Researchers have mapped the Ochoa syndrome gene to a 1-cM interval on chromosome 10q23-q24. Chromosomes, which are present in the nucleus of human cells, carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males, and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into many bands that are numbered. For example, “chromosome 10q23″ refers to band 23 on the long arm of chromosome 10.
Ochoa syndrome affects both sexes equally. The disorder was first identified by and subsequently named after Dr. Bernard Ochoa, a urological surgeon and researcher from Colombia, South America. More than 50 cases have been reported in the medical literature including affected individuals within several multigenerational families (kindreds). According to the literature, the majority of kindreds are from Columbia although affected families have also been reported in the United States (i.e., Massachusetts, California, and Pennsylvania), the United Kingdom, Kuwait, Denmark, and Spain.
Because extremely rare disorders like Ochoa syndrome often go unrecognized, these disorders are under-diagnosed, making it difficult to determine the true frequency of such disorders in the general population.
Some researchers suspect that many infants and children who experience abnormalities of the bladder, hydroureter, hydronephrosis, and associated symptoms may have Ochoa syndrome. However, recent research has revealed that affected individuals with dysfunctional bladder without the characteristic facial findings may not be in the category of Ochoa syndrome because their genetic patterns are typically different.
Ochoa syndrome may be diagnosed before or after birth by genetic analysis that may demonstrate the presence of unidentified genetic material (microsatellite genetic markers) at the long arm of chromosome 10 in the vicinity of the disease gene (10q23-q24).
At birth, the first feature that may be apparent in affected infants is the “inverted” facial expression. Due to the strong association of this feature and urological abnormalities, the presence of inverted facial expressions should lead to a prompt, thorough examination of the urinary tract. Such evaluation may lead to early diagnosis of Ochoa syndrome and specific associated features (e.g., urinary tract infection), playing an essential role in ensuring appropriate preventive steps and/or prompt treatment.
During such urological evaluation, specialized imaging techniques may be used to examine the structure and assess the function of organs within the urinary tract (e.g., different portions of the kidneys, the bladder, the ureters). Such tests may include intravenous pyelography (IVP), during which a special contrast medium is injected and x-rays are then taken, and urodynamic evaluation, which examines the movement and flow of liquids through the urinary tract.
In addition to neuropathic bladder and obstructive abnormalities, such specialized imaging studies may also reveal structural abnormalities of the urinary tract. The bladder may have abnormal, anchoring bands and cords of connective tissue (trabeculation) and demonstrate overgrowth (hypertrophy) and abnormal hardening (sclerosis) of mucuous membranes (mucosa), causing small sac-like protrusions (hernias) of tissue through the bladder's muscular wall (diverticula). In addition, the bladder's outer muscular layer (detrusor urinae muscle) may demonstrate unusually increased reflex reactions (hyperreflexia) and abnormal, prolonged contractions (hypertonic contractures); the neck of the bladder may be abnormally enlarged (hypertrophic); and/or the urethra may have irregular spasms (spastic urethra) and have an abnormal diameter (caliber).
Urinary tract infections may be diagnosed by clinical evaluation, microscopic examination and bacteriological culture of urine specimens, and, in some cases, pyelography and ultrasonography, during which sound waves are used to create images of the urinary tract.
The treatment of Ochoa syndrome is geared toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who specialize in diagnosing and treating disorders of the urinary tract (urologists), physicians who specialize in disorders of the kidneys (nephrologists), surgeons, dietitians, and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment.
In many cases, therapy for urinary tract infections associated with Ochoa syndrome includes antibiotics for the treatment and prevention of bacterial infections and pain relievers (e.g., analgesics). In some cases, surgery may be conducted to eliminate urinary tract obstruction and reconstruct certain portions of the urinary tract (e.g., ureters, ureterovesicular junction). The surgical procedures performed depend upon the severity of the anatomical abnormalities and their associated symptoms.
In affected children who experience chronic renal failure, treatment options may include certain procedures that regularly remove excess waste products from the blood (dialysis). Such procedures may include the removal of wastes by filtering the blood through a machine (hemodialysis) and/or by using a natural filtering membrane in the body's abdomen (peritoneal dialysis). In some cases of severe renal failure, kidney transplantation may be considered.
Early intervention is important to ensure that affected children reach their potential. Special services that may be beneficial may include special social support and other medical and/or social services.
Genetic counseling will be of benefit for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.
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McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:236730; Last Update:11/16/00.