|Patient: 21 year old female|
|History: 21 year old female with an achondroplastic form of micro-dwarfism (skeletal dysplasia) and a history of multiple arterial aneurysms. History of mitral valve disease with mitral valve replacement. History of connective tissue disorder and multiple congenital anomalies including urologic and orthopedic anomalies. She required bilateral open knee reductions at the age of nine months. She has also undergone uteric reimplants, for management of vesicoureteral reflux, as well as a soft palate augmentation, and has had recurrent bacterial sinusitis, and has chronic pain related to the ongoing arterial insufficiency in her lower extremities, migraine headaches, and recurrent ovarian cysts. |
The patient is one of three surviving children. She had an younger female sibling who died of the same condition in the neonatal period. She has a brother with a history of exertional migraine, and there is a family history of migainous headaches affecting her maternal aunt and maternal grandfather, although not her mother.
ANGIOGRAPHY OF MULTIPLE VESSELS - 10/08/1996:
ANGIOGRAPHIC FINDINGS: THE INITIAL PULMONARY CONTRAST INJECTION PRODUCED GOOD OPACIFICATION OF THE THORACIC AND ABDOMINAL AORTA AND THE MAJOR PROXIMAL BRANCHES. THE VENOUS PHASE INITIALLY DEMONSTRATED MODERATE ENLARGEMENT OF THE LEFT ATRIUM WITH NO SIGNIFICANT OBSTRUCTION AT THE MITRAL VALVE. THE LEFT VENTRICLE APPEARED NORMAL IN SIZE WITH GOOD CONTRACTILITY. THERE WAS MILD DILATATION OF THE ASCENDING AORTA AND TORTUOSITY OF THE DESCENDING AORTA. THE BRACHIOCEPHALIC ARTERIES WERE ALL PATENT. THE LEFT SUBCLAVIAN ARTERY WAS NORMAL IN APPEARANCE AS WAS THE LEFT COMMON CAROTID ARTERY, ALTHOUGH THERE APPEARED TO BE A SMALL ANEURYSM FROM AN EXTERNAL CAROTID BRANCH ON THE LEFT SIDE. THERE WAS FUSIFORM DILATATION OF THE RIGHT INNOMINATE ARTERY AFFECTING THE ORIGINS OF THE COMMON CAROTID AND SUBCLAVIAN ARTERIES. THE SUBCLAVIAN AND AXILLARY ARTERIES DISTAL TO THIS APPEARED NORMAL. AT THE LEVEL OF THE RIGHT UPPER EXTREMITY THERE APPEARED TO BE OCCLUSION OF THE PROXIMAL RADIAL ARTERY WITH THE COLLATERALS PRODUCING OPACIFICATION OF THE DISTAL PORTION OF THIS VESSEL. THE ULNAR ARTERY WAS REPLACED BY COLLATERALS IN ITS MORE DISTAL EXTENT. THERE WERE A FEW TINY ANEURYSMS OR VESSEL TORTUOSITIES SEEN IN THE REGION OF THE PROXIMAL RADIAL ARTERY. THE VENOUS PHASE DEMONSTRATED A GOOD SIZED CEPHALIC SYSTEM WITH OCCLUSION OF THE BRACHIAL VEIN AT THE LEVEL OF THE ANTECUBITAL FOSSA. IN THE LEFT UPPER EXTREMITY THE BRACHIAL ARTERY APPEARS TO HAVE BEEN OCCLUDED ABOVE THE ELBOW AND REPLACED BY TORTUOUS COLLATERALS CONNECTED MAINLY TO THE ULNAR ARTERY. THERE IS RETROGRADE FILLING OF THE ULNAR ARTERY FROM THE CARPAL ARCADE AND ALSO ANTEGRADE FILLING VIA COLLATERALS AROUND THE ELBOW. THERE IS A SMALL ANEURYSM OF A COLLATERAL VESSEL ABOVE THE ANTECUBITAL FOSSA AND THERE IS LATE OPACIFICATION OF A MULTILOBED ANEURYSM IN THE POPLITEAL FOSSA ITSELF, PROBABLY ARISING FROM THE ORIGIN OF THE RADIAL ARTERY. AT THE LEVEL OF THE ABDOMEN, THE ABDOMINAL AORTA TAPERS BELOW THE RENAL ARTERIES. THE MAJOR VISCERAL BRANCHES WERE PATENT. THERE IS FUSIFORM ANEURYSM FORMATION OF THE ORIGIN OF THE CELIAC ARTERY AND, TO A VERY MINOR DEGREE, THE SMA, WITH NORMAL FILLING OF THE BRANCHES. THE RENAL ARTERIES APPEAR NORMAL. THERE APPEARS TO BE SEPARATE ORIGIN OF THE RIGHT EXTERNAL AND INTERNAL ILIAC ARTERIES. THE RIGHT EXTERNAL ILIAC ARTERY HAS A LARGE ANEURYSM JUST DISTAL TO ITS ORIGIN, FOLLOWED BY TWO SMALLER ANEURYSMS OF THE COMMON FEMORAL ARTERY ABOVE THE HIP. THE RIGHT SUPERFICIAL FEMORAL ARTERY IS OCCLUDED AT ITS ORIGIN AND THROUGHOUT ITS LENGTH, AND THERE IS RECONSTITUTION OF THE ANTERIOR AND POSTERIOR TIBIAL ARTERIES AND THE PERONEAL ARTERY, TO A GENICULATE COLLATERAL. THREE SMALL ANEURYSMS ARE SEEN IN BRANCHES OF THE PROFUNDA FEMORAL ARTERY ON THE RIGHT. ON THE LEFT SIDE, THE EXTERNAL ILIAC ARTERY, COMMON FEMORAL AND SUPERFICIAL FEMORAL ARTERIES ARE OCCLUDED DOWN TO JUST BELOW THE KNEE. THERE IS A LARGE ANEURYSM ARISING FROM THE AORTIC BIFURCATION AND SMALL ANEURYSM OF ONE OF THE GLUTEAL BRANCHES. COLLATERALS FROM THE GLUTEAL ARTERIES PLUS INFERIORLY ALONG THE LATERAL THIGH AND REOPACIFY THE RUN-OFF VESSELS (ANTERIOR AND POSTERIOR TIBIAL ARTERIES IN THE CALF). THERE IS AN ANEURYSM OF WHAT APPEARS TO BE THE LATERAL PLANTAR ARTERY IN THE LEFT FOOT.
SUMMARY: MULTIPLE VASCULAR OCCLUSIONS AND ANEURYSMS AS DESCRIBED
MRI OF THE ABDOMEN AND THIGHS - 4/4/01:
FINDINGS: Multiple arterial aneurysms are identified. These include a 3.3 x 4.4 cm aneurysm in the right medial proximal thigh, likely originating from the deep right femoral artery. A 1.9 x 2.3 cm aneurysm in the anterior aspect of the right thigh, in the region of the superficial femoral artery, is new. There is slight increase in the size of an aneurysm in the right lower pelvis, which measures 4.3 x 5.2 cm, as compared to 4.0 x 4.5 cm previously, which likely originates in the right internal iliac artery. This aneurysm also appears more thrombosed than previously. There is no significant change in an aneurysm in the left pelvis which measures 2.8 x 2.6 cm, likely originating from the left common iliac artery. A lower abdominal aneurysm which measures 5.2 x 4.7 cm appears to have a neck originating from the distal abdominal aorta, just above its bifurcation and then extends superiorly anterior to the more proximal aorta. This aneurysm is slightly larger than previously when it measured 5 x 4.5 cm and is partially thrombosed. The right and left common iliac arteries are not visualized. The right common femoral artery is also absent, probably surgically removed.
A right ovarian cyst measures 3.6 cm transverse x 2.7 cm SI and is new from the prior CT. The left ovarian cyst seen on the prior CT has resolved.
Findings consistent with skeletal dysplasia are again identified. There is a thoracolumbar scoliosis convex to the left, upper lumbar scoliosis convex to the right and a lower lumbar scoliosis convex to the left.
IMPRESSION: Multiple abdominal, pelvic and right thigh aneurysms, as described above, the majority of which are partially or completely thrombosed. An aneurysm in the anterior proximal right thigh is new, while an aneurysm in the right lower pelvis is slightly larger and more thrombosed than previously.
|Diagnosis: The patient has a disorder characterized by multisystemic complications of excessive connective tissue laxity. Complications of this connective tissue disorder include severe global growth failure and multiple arterial aneurysms, which have been complicated by progressive occlusion with resulting vascular insufficiency in the lower extremities. The patient has a known saccular aortic aneurysm, bilateral iliac aneurysms, a popliteal aneurysm and aneurysms affecting the arteries of the upper extremities. In addition, the patient has bilateral moderately severe conductive hearing loss, congenital nystagmus and profound myopia. Genetic diagnosis of Larsen's Syndrome.|
The patient died from a rupture of a right brachial aneurysm (2002).
|Discussion: General Discussion|
Larsen syndrome is a rare genetic disorder in which associated features may vary greatly in range and severity from case to case. However, primary features may include multiple joint dislocations; foot deformities; non-tapering, cylindrically shaped fingers; and/or an unusual facial appearance. In some cases, additional features may be present, such as short stature, additional skeletal abnormalities, incomplete closure of the roof of the mouth (cleft palate), heart defects, hearing impairment, mental retardation, and/or other abnormalities.
Larsen syndrome is present at birth (congenital). The symptoms and severity of the disorder vary from one affected individual to another. Most cases are characterized by a prominent forehead, an upturned nose with a depressed bridge, and slightly protruding wide-spaced eyes. Multiple bone dislocations can occur in the joints of the knees, elbows and hips. The fingers are usually non-tapering and cylindrically shaped. Feet are often clubbed with extremely high arches (pes cavus). Abnormalities of the spine may be present. In males, the testes may be undescended (cryptorchidism).
Some affected individuals may have webbed fingers (syndactyly), low-set ears, short stature, accumulation of fluid in the skull (hydrocephalus), a cleft or high arched palate or lip, fingernail or toenail abnormalities, mild curvature of the spine (scoliosis), or softening of the bones (osteoporosis). Heart or respiratory difficulties may also be present at birth.
Affected individuals may also experience breathing (respiratory) difficulties due to abnormal softening or flaccidness of the cartilage of the voice box (larynx) and the windpipe (trachea), a condition known as laryngotracheomalacia.
Mental retardation has been reported in some cases. Heart (cardiac) abnormalities such as abnormal widening of the aorta (aortic dilatation) and atrial or ventricular septal defects (ASD or VSD) may also be present. The normal heart has four chambers. The two upper chambers, known as atria, are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers are known as ventricles and are separated from each other by the ventricular septum. ASDs or VSDs are abnormal openings in the corresponding septum. The size and location of the defect determine the severity of the symptoms. A small atrial or ventricular septal defect may close on its own (spontaneously) or become less significant as the child matures and grows. Larger defects may result in a variety of symptoms including an abnormally rapid rate of breathing (tachypnea), wheezing, an unusually fast heartbeat (tachycardia), failure to grow at the expected rate (failure to thrive), and/or other findings.
In extremely rare cases, hearing loss and dental abnormalities may also be present.
The specific underlying cause of Larsen syndrome is unknown. However, the disorder is thought to result from a generalized defect of collagen formation. Collagen is a tough, fibrous protein that is the major structural protein in the body. Larsen syndrome may be familial or appear to occur randomly for unknown reasons (sporadically) in the apparent absence of a family history.
In many familial cases, Larsen syndrome appears to be inherited as an autosomal dominant trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.
In autosomal dominant disorders, a single copy of the disease gene (received from either the mother or father) may be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disease gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.
Researchers have conducted genetic analysis of a large Swedish family (kindred) with multiple members affected by autosomal dominant Larsen syndrome. Based on such research, investigators suggest that, in some people with autosomal dominant Larsen Syndrome, a gene for the disorder may be strongly linked to a region on the short arm of chromosome 3 (3p21.1-14.1). Chromosomes are found in the nucleus of all body cells. They 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 bands that are numbered.
In other instances, Larsen syndrome has been reported in more than one child (siblings) of two apparently normal parents. According to some researchers, such cases suggest autosomal recessive inheritance. In addition, a few cases have been reported in which the parents of affected siblings are closely related by blood (consanguineous), further supporting the possibility of autosomal recessive inheritance in some cases of Larsen Syndrome.
In autosomal recessive disorders, the condition may not appear unless a person inherits a defective (mutated) 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. 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.
However, some researchers indicate that there is little evidence for autosomal recessive inheritance in some cases in which affected children are born to apparently normal parents. Such investigators suggest that one parent may in fact have extremely mild symptoms, remaining undiagnosed with the disease. Thus, they indicate that such cases may actually represent autosomal dominant transmission with extremely variable expression.
In addition, some researchers suggest that certain apparently recessive cases may represent germline mosaicism. In germline mosaicism, some of a parent's reproductive cells (germ cells) may carry the gene mutation while others contain a normal cell line ("mosaicism"). As a result, one or more of the parent's children may inherit the gene mutation, potentially leading to manifestation of the disorder, while the parent may have no apparent symptoms (asymptomatic carrier). Germline mosaicism may be suspected when apparently unaffected parents have more than one child with the same genetic abnormality.
Further research is necessary to determine the underlying genetic mechanism(s) responsible for transmission and expression of Larsen syndrome.
Larsen syndrome is named for the investigator Dr. Loren Larsen who originally described the syndrome as a distinct disease entity in 1950. Reported cases include familial and apparently sporadic cases. As noted above, associated symptoms and physical findings may vary greatly among affected individuals, including among members of the same family. The disorder appears to affect males and females in relatively equal numbers.
Courtesy of NORD - website: www.rarediseases.org
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Case Number: 7464001Last Updated: 03-15-2007 The reader is fully responsible for confirming the accuracy of this content.
The reader is fully responsible for confirming the accuracy of this content.