Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that is generally apparent at birth (congenital).
Males and females appear to be affected in equal numbers.
It is estimated that there is a 1-2 % rate of recurrence within affected families.
Cause
Seven genes have been found to be associated with CdLS including the NIPBL gene on chromosome 5, the SMC1A gene on the X chromosome, the SMC3 gene on chromosome 10, the Rad21 gene on chromosome 8, the HDAC8 gene on the X chromosome, the ANKRD11 on chromosome 16 and the BRD4 gene on chromosome 19.
Inherited as an autosomal dominant condition or an X-linked condition.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.
X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and occur mostly in males. Females that have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and one is inactivated so that the genes on that chromosome are nonfunctioning. It is often the X chromosome with the abnormal gene that is inactivated. However, in CdLS, because the gene change is likely dominant over the corresponding gene on the X chromosomes, females also often show similar findings as males.
Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a disease gene he will develop the disease.
Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son. Males with X-linked disorders pass the disease gene to all of their daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.
Most affected individuals have an abnormal gene as a result of a new gene mutation and do not have an affected parent.
A low-pitched “growling” cry and low voice and/or a hoarse voice?
Heart (cardiac) defects/atrial septal defect (‘hole in the heart’):
Short of breath and/or breathing difficulties (whether after exercise or not) and/or wheezing?
Regular and reoccurring chest infections?
Heart palpitations and/or irregular heartbeats?
Short breastbone (sternum)?
Abnormally thin ribs?
“Spit up” food that has already been swallowed (regurgitation) and may experience episodes of severe, forceful vomiting (projectile vomiting)?
Heartburn and indigestion?
Abnormalities of the kidneys/Pain in pelvis area and/or lower back and/or intense pain in the back or side (or moving pain from back to side) or in groin area?
Abnormalities of the penis (opening of penis in wrong place), testicles (failure of testicles to fall to right position), or vagina (Blockage of the vagina)/Underdevelopment or malformation of genitals and urinary tract?
Abnormalities on one side of the body may be completely different from those on the other side (asymmetrical)?
Bone and joint movement problems and/or abnormally exaggerated reflexes (hyperreflexia)and/or difficulty using arms and/or body and/or legs and/or lack of stamina and/or walking difficulties and/or crawling difficulties and/or rolling over difficulties?
Small hands and feet and/or absence of the forearms, hands, and fingers?
Fingers become smaller and thinner toward the ends (tapered fingers)?
Thumbs may be abnormally positioned (i.e.proximally placed) and the arms may be permanently bent or flexed at the elbows due to bone fusions?
Inward deviation (clinodactyly) of the fifth fingers?
Deformity of the hip (coxa valga)?
Webbing (syndactyly) of certain toes (second and third toe)?
Slowed growth and/or shorter than average?
Complications /Information to beware of/General tips:
Fetal alcohol spectrum disorder (FASD) is a syndrome of altered fetal growth resulting in certain birth defects due to maternal consumption of alcohol during pregnancy.
When a pregnant woman drinks alcoholic beverages, a pattern of defects in the fetus may occur at different stages of pregnancy.
Especially in the first three months of pregnancy, increases the risk of miscarriage, premature birth and intrauterine growth restriction.
Drinking after the first trimester affects the baby post-natally.
Drinking heavily (more than six drinks per day) throughout pregnancy.
Foetal alcohol syndrome:
Symptoms of baby include:
Small head
Flat face
Small eye opening
Epicanthal folds (skin fold of the upper eyelid covering the inner corner of the eye)
Short nose
Low nasal bridge
Smooth Philtrum (Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border)
Thin upper lip
Underdeveloped jaw
Genital malformations
Heart (cardiac) defects
Infants often experience alcohol addiction withdrawal symptoms , this may include tremors and/or convulsions, irritability, increased muscle tone, muscle and/or whole body spasms, increased respiratory rate, abdominal swelling (distention) and/or vomiting
Joint abnormalities
Ruvalcaba syndrome is a very rare disorder thought to be inherited as an autosomal dominant genetic trait. The symptoms vary greatly among individuals with the disorder. Characteristic facial features are among the most distinguishable symptoms of this disorder. Affected individuals may have an abnormally small head (microcephaly) with an oval face; downslanting eyelid folds; abnormalities of the nose; a small, downturned mouth; a narrow, pointed jaw; and/or low-set ears. Additional features may include short stature; a narrow chest; protruding breastbone (pectus carinatum); abnormal sideways and/or front-to-back curvature of the spine (scoliosis and/or kyphosis); short fingers, toes, arms, and/or legs; abnormally small hands and feet; and/or abnormal bending of the fingers (clinodactyly). Affected individuals may also have certain skin abnormalities, underdevelopment (hypoplasia) of the reproductive organs, delayed puberty, and/or other physical abnormalities. Many individuals with Ruvalcaba syndrome may also have varying degrees of intellectual disability.
Scott craniodigital syndrome with intellectual disability is an extremely rare disorder that is thought to be inherited as an X-linked recessive genetic trait. This disorder is characterized by intellectual disability and various physical abnormalities affecting the head and facial (craniofacial) area and the fingers and/or toes (digits). Characteristic craniofacial features may include a short, wide head (brachycephaly); a small, narrow nose; widely-spaced eyes (ocular hypertelorism); and/or an abnormally small lower jaw (mandible). In addition, some children may have a “startled” expression to their faces. Other characteristic features may include webbing of some of the fingers and toes (syndactyly); uncommon skin ridge patterns (dermatoglyphic patterns) on the palms of the hands; and/or abnormal inward turning of the heel of the foot (talipes varus). In addition, individuals with this disorder may have scalp hair that is very thick with hair growing down onto the temples and in front of the ears; long, dark eyelashes; abnormally thick eyebrows; and/or excessive hair growth (hirsutism) on other areas of the body.
Duplication on the long arm of chromosome 3, or partial trisomy 3q2, is an extremely rare chromosomal disorder in which the end (distal) portion of the long arm (q) of chromosome 3 (3q) is present three times (trisomy) rather than twice in cells of the body. This disorder is characterized by abnormalities of the head and facial (craniofacial) area, other physical malformations, moderate to severe developmental delays, and/or intellectual disability. Many of the craniofacial abnormalities and/or other physical malformations associated with partial trisomy 3q2 are very similar to those often associated with CdLS. For example, many infants and children with partial trisomy 3q2 may have an abnormally small head (microcephaly) that also appears unusually short and wide (brachycephaly); a low hairline; a small, broad nose; thick, well-defined, bushy eyebrows that grow together (synophyrys); long eyelashes; and/or thin, downturned lips. Affected infants and children may also have excessive hair growth (hypertrichosis) on various areas of the body; abnormalities of the hands, feet, arms, and/or legs; hearing loss and speech impairment; and/or eye (ocular) abnormalities including crossing of the eyes (strabismus), rapid, involuntary eye movements (nystagmus), clouding of the lenses of the eyes (cataracts), and/or other ocular abnormalities. Individuals with partial trisomy 3q2 may also have seizure episodes and/or genital, heart (cardiac), gastrointestinal, and/or kidney (renal) malformations. In most children, partial trisomy 3q2 is due to a balanced translocation in one of the parents.
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Detailed Information
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