Define Cornelia de Lange syndrome
Cornelia de Lange syndrome (CdLS) is a congenital rare syndrome appear due to genetic disorders. The primary characteristic of this syndrome is delayed physical development during fetal growth and continues to after birth. In other word, it can be described as a prenatal and postnatal growth retardation.
The signs and symptoms are associated with distinct physical appearance, including craniofacial (head and facial) abnormalities, defective upper limb (hands and arms) development; and mild to severe cognitive impairment due to mental retardation. The symptomatic variation seems with case to case. (1,2)
Sign and symptoms
The typical sign and symptoms of Cornelia de Lange syndrome is distinct, but some features are considered as secondary features. Therefore, the appeared signs and symptoms are divided into two categories, which include primary characteristics and secondary characteristics, though all the below mentioned sign and symptoms may not be prominent in every case.
Primary characteristics of CdLS
Depending upon the genetic differences, the primary characteristics occur, which include:
Overall growth of a infants
The infant born by CdLS usually has low birth weight, that approximately 5 lbs. or 1oz., but this is not a fixed for every case, and it varies within a range of 1 lb., 2 oz. to 10 lbs. The length of the child is also low and calculated mean birth length is around 18 inches. The provided value can help to indicate that CdLS cause growth retardation during fetal development in the womb. The head size of the infant is also small, which is termed as microcephaly.
Delayed mental development
The children with CdLS typically has delayed mental development and cause mild to severe intellectual incapacitance. The common features include Learning disabilities, language delays, but some individual can have borderline of standard intelligence.
Gastro esophageal Reflux Disease (GERD)
Vast majority of the CdLS patient (almost 85%) complains discomfort after ingestion of food, like heartburn due to the high possibility of GERD. The unpleasant effect also has a negative impact on behavior.
Different types of annoying behaviors, which may cause self hurting issues like head-banging or hand-biting are often associated. Repetitive compulsive behavior, Obsessive Compulsive Disorder, Attention Deficit Hyperactivity Disorder, Anxiety and Attention Deficit Disorder are also noticeable with patients having CdLS syndrome.
Secondary Characteristics of CdLS
Typical facial appearance
Along with microcephaly, a peculiar vertically extended groove present between the upper lip and nose, a stumpy nasal bridge; upturned nostrils; and a obtrude upper jaw. In addition, distinctive facial defects may consist of skinny, downturned lips; ears are low-sited; vaulted, prominent eyebrows that raise jointly diagonally from the bottom of the nose; an oddly short hairline on the forehead and the backside of the neck; and atypical twisted, elongated eyelashes and cleft palate or high-arched palate.
The typical distinction of limb is also associated with CdLS patients, for them, which include small sized hands and feet with curved little finger (clinodactyl), incompletely united the second and third toes, abnormal positioning of the thumbs. Associated hand abnormalities may be single sided or both sided. Foot size is smaller than the normal size. Other than these, rarely missing of fingers, forearms or hands are noticed.
Other System Abnormalities
Other included abnormal features include inflamed eyelid, drooping eyelids, myopia (nearsightedness), involuntary rapid eye movement etc. (2,3,4)
Cornelia De Lange Syndrome Causes
The Cornelia de Lange syndrome is a genetic disorder. The responsible genes associated with CdLS are NIPBL gene on chromosome 5 and the SMC1L1 gene on the X chromosome. In most of the cases, almost half of the incidence is related to the abnormal mutation NIPBL gene, though a very few cases are associated with the abnormal mutation of SMC1L1 gene. Other involved gene yet to discover.
The mutagenic abnormality of the involved gene may carry forward from either of the parental source or new genetic alteration also cause the onset of CdLS. (2)
An ultrasound imaging system may help to assume the presence of Cornelia de Lange syndrome (CdLS) during fetal growth. The waves of the ultrasounds form an image, which can detect growth retardation, deformities of limb, facial abnormalities and/or defective organ formation.
The confirmation can be notable about the presence CdLS is possible after the birth of the infant by performing a thorough clinical evaluation and detection of typical physical features. The different scientific literature described that a confirmed diagnosis of the presence of Cornelia de Lange syndrome can be reported after receiving the distinct facial features with the association of limb abnormalities, before and after birth growth retardation, and intellectual retardation. Mild symptomatic features can cause confusion of the CdLS diagnosis and often difficult to provide conclusive result.
In confirmatory test, molecular genetic testing is performed in the NIPBL and SMC1L1 and finding of abnormal genetic mutations validate the detected physical abnormality is related to CdLS. This test usually recommended for mild characteristic features.
If a precise NIPBL or SMC1L1 gene mutation has been detected, then in the prenatal stage diagnosis of CdLs is possible. (2,4)
Depending upon the notable symptomatic approach, a treatment plan is prepared by the clinical experts. In the Cornelia de Lange syndrome, multiple organ deformity is involved, therefore a team of expert clinicians needs to provide a proper therapeutic approach to the affected child. The included specialists are pediatricians; surgeons; geneticists; orthopedists; orthopedic surgeons; plastic surgeon; gastroenterologists, urologists, otolaryngologists (specialist of the ears, nose, and throat); pediatric cardiologists; dentist; speech pathologists; audiologists (specialists who assess and treat hearing problems); eye specialists; physical and occupational therapists; and/or other health care givers.
Any involvement of cardiac problems, GI tract defect, audibility complications, and/or propensity towards respiratory infections need early detection and prompt medical care to reduce the complications. The interventions include pharmacological, surgical depending upon the site and type of abnormality. For example, child susceptible towards respiratory infection can need to treat with antibiotic therapy, episodes of convulsion can be controlled by anticonvulsive therapy, whereas abnormality in heart or limb abnormality may rectify by surgical intervention.
Other supportive therapeutic approaches like hearing aids may recommend and provide a beneficial effect for hearing impairment. Remedial education, speech therapy, vocational training, and/or other medical and/or social services also provide positive outcomes for CdLS.
Genetic counseling is suggested for affected persons and their family members. (2)
- Cornelia de Lange syndrome, (2016); Genetic Home References; Retrieve from: https://ghr.nlm.nih.gov/condition/cornelia-de-lange-syndrome
- Cornelia de Lange Syndrome; National Organization for rare diseases; http://rarediseases.org/rare-diseases/cornelia-de-lange-syndrome/
- Characteristics of CdLS; CdLS foundation; http://www.cdlsusa.org/what-is-cdls/characteristics-of-cdls.htm
- Matthew A Deardorff, Sarah E Noon, andIan D Krantz, (2016); Cornelia de Lange Syndrome; http://www.ncbi.nlm.nih.gov/books/NBK1104/