CdLS is a very rare disorder characterized by growth delays; distinctive facial features; malformations of the hands, feet, arms, and/or legs (limb anomalies); other physical abnormalities; intellectual disability; and/or developmental delays. The range and severity of symptoms and physical characteristics may vary greatly from person to person.
Individuals with CdLS exhibit abnormal growth delays that affect both weight and linear growth before and after birth (prenatal and postnatal growth retardation). Most affected infants may have a low birth weight and may fail to gain weight or grow at the expected rate (failure to thrive). CdLS growth charts are available to compare growth to other affected individuals. Individuals may experience feeding, chewing, and swallowing difficulties during the first several months/years of life.
Many affected infants may frequently “spit up” food that has already been swallowed (regurgitation) and may experience episodes of severe, forceful Vomiting (projectile vomiting). Infants with CdLS may also demonstrate abnormally increased muscle tone (hypertonicity) and have an unusual, low-pitched, growling cry.
Individuals with CdLS also have distinctive features of the head and facial (craniofacial) area including an abnormally Small head (microcephaly) that may also be unusually short (brachycephaly); a short, thick neck; a low hairline; a small, broad, upturned nose with nostrils that tip upwards (anteverted nares); neat, arched eyebrows that grow together (synophrys); long, curly eyelashes; and/or excessive hair growth on various areas of the body (hypertrichosis). Additional features may include thin, downturned lips; an abnormally long vertical gap between the upper lip (philtrum) and the nose; an abnormally small, underdeveloped jaw (micrognathia); late-erupting, widely-spaced, unusually small teeth; and low-set ears. In some cases, affected infants may also exhibit incomplete closure of the roof of the mouth (cleft palate), a hidden incomplete closure (submucous cleft palate) and/or a highly arched palate.
In most infants with CdLS, the hands and feet are small for their size. In addition, affected individuals may have short fingers that become smaller and thinner toward the ends (tapered fingers), fifth fingers that are permanently curved toward the ring finger (clinodactyly), and/or, in some people, absence of one or more fingers (oligodactyly). The 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. In addition, in many cases, affected individuals may demonstrate underdevelopment (hypoplasia) of some of the bones of the fingers and toes, and the second and third toes are often abnormally fused or webbed (syndactyly). Some affected infants may also have, in rare cases, fingers, hands, and forearms which are missing. In individuals with CdLS, upper limb abnormalities may involve one side (unilateral) or both sides (bilateral) of the body. If bilateral limb malformations are present, the abnormalities on one side of the body may be completely different from those on the other side (asymmetrical). Although the feet are small, only in extremely rare cases are there absent bones in the feet or lower legs.
Individuals with CdLS also demonstrate delayed bone age (retarded osseous maturation). In addition, affected individuals may remain low in weight and exhibit abnormally Short stature (prenatal and postnatal growth retardation), Failure to thrive during infancy, delayed bone age, and/or other abnormalities. Many individuals with CdLS also exhibit additional skeletal abnormalities. These may include a deformity of the hip (coxa valga), a short breastbone (sternum), and/or abnormally thin ribs.
Many infants and children with CdLS may exhibit delays in the acquisition of skills requiring the coordination of mental and muscular activity (psychomotor retardation), have mild to severe intellectual disability, and/or demonstrate behavioral problems (e.g., episodes of biting, screaming, hitting themselves, etc.). In addition, although affected children may have decreased facial expression based on emotion, they appear to respond positively to certain stimuli (e.g., fast movements). A CdLS developmental chart is available to compare milestones.
Many children with CdLS also have hearing impairment as well as abnormal speech development. Middle ear infections (otitis media), which sometimes occur chronically with an accumulation of sticky fluid (otitis media with effusion or glue ear), are common. Younger children may have Difficulty speaking (dysphonia and/or apraxia), while older children may have abnormally hoarse speech.
Many individuals with CdLS also exhibit additional physical abnormalities. In many cases, the skin may appear “marbled” (cutis marmorata), and the skin above the eyes, mouth, and nose may have an unusual bluish tone. In addition, many affected individuals demonstrate irregularities in the skin ridge patterns on the palms of the hands (dermatoglyphics). As mentioned earlier, most affected individuals may exhibit excessive hair growth (hypertrichosis) on various areas of the body including the ears. Hair may also tend to appear on the lower back, limbs, and/or other areas of the body.
Many individuals with CdLS also have various abnormalities of the gastrointestinal system including gastroesophageal reflux, a condition in which the acidic contents of the stomach flow upward into the lower esophagus; Inflammation of the lining of the esophagus (esophagitis); and/or narrowing of the esophagus (esophageal stenosis). In addition, affected individuals are at risk for abnormal twisting (malrotation) of the intestines, potentially causing intestinal obstruction (volvulus). In some children, the bands of muscle fibers (pyloric sphincter) at the junction between the stomach and small intestine (pyloric stenosis) may become abnormally narrowed (stenosis) in infancy, resulting in obstruction of the normal flow of stomach contents into the small intestine. In addition, some individuals with CdLS may also have protrusion of portions of the large intestine through an abnormal opening in musculature lining the abdominal cavity in the area of the groin (inguinal hernia) and/or part of the stomach through an abnormal opening where the esophagus passes through the diaphragm (hiatal hernia). Some babies with CdLS can be born with diaphragmatic hernia, in which some of the contents of the abdomen have not been separated from the lungs as a fetus; this needs to be repaired for survival. In some individuals with CdLS, certain gastrointestinal abnormalities may lead to intestinal obstruction, potentially causing serious or life-threatening complications if left untreated.
Some individuals with CdLS may also have malformations of the genitourinary tract. In affected males, such abnormalities may include underdevelopment (hypoplasia) of the genitals, failure of one or both of the testes to descend into the scrotum (cryptorchidism), and/or abnormal placement of the urinary opening (urinary meatus) on the underside of the penis (hypospadias). Affected females may have abnormal development of the uterus (e.g., bicornate or septate uterus), and menstruation may be irregular.
Many children with CdLS have additional physical abnormalities including various heart (cardiac) abnormalities. Some affected individuals may also have an increased susceptibility to repeated respiratory infections, Eye abnormalities such as nearsightedness (myopia), rapid, involuntary eye movements (nystagmus), and/or abnormal drooping of the upper eyelid(s) (ptosis). Some infants and children with CdLS may also experience episodes of uncontrolled electrical disturbances in the brain (seizures).