Seckel syndrome is an extremely rare inherited disorder characterized by growth delays prior to birth (intrauterine growth retardation) resulting in low birth weight. Growth delays continue after birth (postnatal), resulting in short stature (dwarfism). Other symptoms and physical features associated with Seckel syndrome include an abnormally small head (microcephaly); varying degrees of mental retardation; and/or unusual characteristic facial features including "beak-like" protrusion of the nose. Other facial features may include abnormally large eyes, a narrow face, malformed ears, and/or an unusually small jaw (micrognathia). In addition, some affected infants may exhibit permanent fixation of the fifth fingers in a bent position (clinodactyly), malformation (dysplasia) of the hips, dislocation of a bone in the forearm (radial dislocation), and/or other physical abnormalities.
Seckel syndrome is characterized by abnormally slow growth during fetal development (intrauterine growth retardation), resulting in low birth weight. Unusually slow growth (growth retardation and delayed bone maturation) continues after birth (postnatal) and typically leads to short stature (dwarfism) with proportional development of the arms and legs (as opposed to short stature with abnormally small arms and legs, i.e., short-limbed dwarfism). Moderate to severe mental retardation may also be present at birth (congenital) but may not become apparent until an affected child is older.
In addition, infants with Seckel syndrome have distinctive abnormalities of the head and facial (craniofacial) area. In most cases, affected infants may have microcephaly, a condition that indicates that the head circumference is smaller than would be expected for an infant’s age and sex; a receding forehead; an unusually small jaw (micrognathia) that is recessed farther back than usual (retrognathia); and/or a curved, triangular “beak-like” nose. Due to such abnormalities the middle portion of the face may appear unusually prominent. In addition, in some cases, certain fibrous joints between the bones of the skull (cranial sutures) may close prematurely (craniosynostosis). As a result, the head may appear abnormally elongated or shortened, depending on which part of the skull is affected.
In some infants with Seckel syndrome, other craniofacial abnormalities may be present including unusually large eyes with downwardly slanting eyelid folds (palpebral fissures); crossed eyes (strabismus); low-set, malformed (dysplastic) ears with absent ear lobes; and/or a highly-arched roof of the mouth (palate) that may be incompletely formed (cleft palate). In addition, in some cases, one side of the face may appear larger than the other (facial asymmetry). Some affected infants and children may have dental abnormalities including underdevelopment (hypoplasia) of tooth enamel and/or crowding and/or improper positioning of the teeth.
In addition, some children with Seckel syndrome may have various skeletal abnormalities including dislocation of the head of the forearm bone on the thumb side of the hand (radial dislocation), dislocation of the elbows, dislocation and/or malformation (dysplasia) of the hips, and/or an inability to fully extend the knees. In some cases, affected children may develop abnormal front-to-back and/or side-to-side curvature of the spine (kyphoscoliosis). Additional skeletal abnormalities may include permanent fixation of the fifth fingers in a bent position (clinodactyly), malformation of the foot in a twisted position (clubfoot), and/or absence of one pair of ribs (i.e., exhibit 11 rather than 12 pairs of ribs).
In some cases, males with Seckel syndrome may exhibit failure of the testes to descend normally into the scrotum (cryptorchidism) and/or affected females may have an abnormally enlarged clitoris (clitoromegaly). In addition, affected children may have excessive body hair (hirsutism), and/or a single, deep crease across the palms of the hands (simian crease).
In some cases, individuals with Seckel syndrome may also have associated blood (hematological) disorders including deficiency of all bone marrow elements including red blood cells, white blood cells, and platelets (pancytopenia). A low level of circulating red blood cells is known as anemia.
Seckel syndrome is an extremely rare disorder that is inherited as an autosomal recessive trait. Three variants of Seckel syndrome involve disruptions or changes (mutations) of genes on three different chromosomes. The gene map locations are: Seckel syndrome 1, on chromosome 3 (3q22-q24); Seckel syndrome 2, on chromosome 18 (18p11.31-q11) and Seckel syndrome 3, on chromosome 14 (14q21-q22).
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 3q22-q24” refers to a region between band 22 and band 24 on the long arm of chromosome 3. In a like manner, “chromosome 18p11.31-q11.2” refers to a broader region between band 11p31 on the short arm of chromosome 18 and band 11.2 on the long arm of chromosome 18. Again, chromosome 14q21-q22 refers to a narrower region on the long arm of chromosome 14 between bands 21 and 22. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
The specific gene involved in Seckel syndrome 1 is known as the ataxia-telangiectasia and Rad3-related protein (ATR) gene. The genes involved in Seckel syndrome types 2 and 3 are unknown.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal 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 for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Seckel syndrome is an extremely rare inherited disorder that appears to affect males and females in equal numbers. The exact incidence of this disorder is now known. More than 100 cases have been reported in the medical literature since its original description in 1960.
With the advent of technically superior ultasonography, Seckel syndrome may be diagnosed before birth (prenatally). In fetal ultrasonography, reflected sound waves are used to create an image of the developing fetus. After birth, Seckel syndrome may be suspected based upon a thorough clinical evaluation, a detailed patient history, and a variety of specialized tests. Although distinctive craniofacial, skeletal, and/or other physical abnormalities associated with Seckel syndrome may be present at birth (congenital), a diagnosis of Seckel syndrome may not be confirmed, in some cases, until an affected child ages and the full syndrome develops (e.g., when short stature and/or mental retardation becomes apparent).
Short stature associated with Seckel syndrome involves proportional growth of the arms and legs, which allows for differential diagnosis from syndromes that involve short stature and abnormally small arms and legs (short-limbed dwarfism).
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