Children with Cornelia de Lange syndrome often present with unusual facial features that develop within a few weeks to months after birth. There is slowed growth combined with development of several other abnormalities which have been described below:
- Children with CdLS present with distinct facial features characterized by anteverted nostrils, thin lips, arched eyebrows, long eyelashes and long philtrum.
- Under developed upper extremities
- Severe amount of body hair
- Hearing problems
- Low birth weight
- Small size of head
- Small stature
- Problems in vision
- Cleft palate
- Behavioral problem 
- Self-injurious behavioral patterns 
- Hearing defects
- Communication problems 
- Hypoplastic genitalia
- Hands and feet are small
- Feeding problems
- Gastrophageal reflux
Entire Body System
- Feeding Difficulties
Cornelia de Lange syndrome (CdLs), which is also called Brachmann de Lange syndrome, is a congenital disorder characterized by distinctive facial features, prenatal and postnatal growth deficiency, feeding difficulties, psychomotor delay, behavioral problems [ncbi.nlm.nih.gov]
Cornelia de Lange syndrome (CdLS) is a syndrome of multiple congenital anomalies characterized by a distinctive facial appearance, prenatal and postnatal growth deficiency, feeding difficulties, psychomotor delay, behavioral problems, and associated malformations [emedicine.medscape.com]
- Atrial Septal Defect
such as atrial septal defect or tetralogy of Fallot Eye problems, including blepharitis (inflammation of the eyelid), ptosis (drooping eyelids) or myopia (near sightedness). [dermnetnz.org]
Cardiovascular disease Congenital malformations of the heart occur in about 46%. Most common are ventricular septal defect, atrial septal defect, pulmonary stenosis and Fallot's tetralogy. The significance varies from minor to fatal. [patient.info]
It is not unusual in CdLS for congenital heart diseases (ventricular or atrial septal defects, aortic or pulmonary stenoses, tetralogy of Fallot, atrioventricular canal, single ventricle, and aortopulmonary window) to be associated with each other. [hindawi.com]
Extensive clinical evaluation and WES of 32 Turkish patients clinically diagnosed with CdLS revealed the presence of a de novo heterozygous nonsense KMT2A mutation in 1 patient without characteristic WDSTS features. [ncbi.nlm.nih.gov]
Key words: Cornelia de Lange syndrome, dehydration hypernatremia, semilobar holoprosencephaly Article Language: Turkish English [bibliomed.org]
In one study, a de novo KMT2A pathogenic variant was found in one out of 32 Turkish patients clinically diagnosed with Cornelia de Lange syndrome (Yuan et al. 2015. PubMed ID: 25574841). [preventiongenetics.com]
Optic pallor and a poor macular reflex have also been reported. [disorders.eyes.arizona.edu]
Nine individuals in our cohort had known optic nerve abnormalities (such as cupping, tilted optic discs, pallor, hypoplasia, staphyloma, and coloboma), 4 of whom were mutation positive and 5 of whom were mutation negative. [jamanetwork.com]
Here we present for the first time a case of BDLS from Sudan, a 7-month-old female infant, who was referred as a case of malnutrition. The patient was from a Sudanese western tribe. [ncbi.nlm.nih.gov]
Growth Parameters • Weight of 6kg • Height of 73.5 cm • Head circumference of 38 cm S/O grade IV malnutrition, with microcephaly and short stature. Systemic examination was normal. Basic Blood investigations and 2D Echo was normal. [nijp.org]
His report was based on the clinical and autopsy features of an who died of pneumonia at the age of 19 days. [whonamedit.com]
Main causes of death in such patients include pneumonia along with cardiac, respiratory and GI abnormalities. [ncbi.nlm.nih.gov]
Respiratory causes, including aspiration and pneumonia, are the most common primary causes (31%) followed by gastrointestinal disease, including obstruction/volvulus (19%). [patient.info]
Other medical features that should be considered in the medical follow-up are tendency to overweight/frank obesity, constipation, discrepancy of limbs' length, epilepsy, hearing, and visual problems. [ncbi.nlm.nih.gov]
These can include vomiting, intermittent poor appetite, constipation, diarrhea or gaseous distention. The gastrointestinal symptoms range from mild to severe. [ucdmc.ucdavis.edu]
[…] to form a single eyebrow Long eyelashes Low-set ears Small wide-spaced teeth Small upturned nose Other features include: Small head size Short stature Excessive hair growth (hirsutism) Gut symptoms such as episodes of loss of appetite, vomiting, or constipation [news-medical.net]
The majority of those affected have diminished sucking and swallowing capacity, failure to thrive, predisposition to respiratory tract infections, and frequent vomiting with aspiration pneumonia. Mental retardation is usually severe. [whonamedit.com]
These can include vomiting, intermittent poor appetite, constipation, diarrhea or gaseous distention. The gastrointestinal symptoms range from mild to severe. [ucdmc.ucdavis.edu]
[…] in the middle to form a single eyebrow Long eyelashes Low-set ears Small wide-spaced teeth Small upturned nose Other features include: Small head size Short stature Excessive hair growth (hirsutism) Gut symptoms such as episodes of loss of appetite, vomiting [news-medical.net]
[…] uterus) hypoplasia of male genitalia with undescended testes or hypospadias seizures (11-23%) congenital heart defects (20-25%) cleft palate or high arched palate (18-59%) feeding difficulties (chewing & swallowing problems, regurgitation, projectile vomiting [en.wikibooks.org]
- Abdominal Pain
An 18-year-old female with Cornelia De Lange syndrome and abdominal pain was found to have a hematometra on ultrasound examination. [ncbi.nlm.nih.gov]
Consider obstruction Because intestinal volvulus is relatively common in children with CdLS, acute abdominal pain, abdominal distention, and/or bilious emesis should prompt immediate evaluation for obstruction. [medicalhomeportal.org]
- Loss of Appetite
[…] of appetite, vomiting, or constipation Causes CdLS is caused by mutations in the NIPBL gene in 65% of patients. [news-medical.net]
- Pansystolic Murmur
On cardiac auscultation was heard 1–2/6 pansystolic murmur. Ophtalmologic examinations revealed normal findings. [nijp.org]
On cardiac auscultation was heard 1–2/6 pansystolic murmur. Ophtalmologic examinations revealed normal findings. Figure 1 Appearance of facial features of case. Figure 2 Appearance of the case. [casesjournal.biomedcentral.com]
Jaw & Teeth
- Small Widely Spaced Teeth
Characteristic craniofacial features include well-drawn and arched eyebrows, sinophria, lengthening of the eyelashes, inverted nostrils, small, widely spaced teeth, micrognathia, and microcephaly. IQ usually ranges from 30 to 120 (average 53). [gsdinternational.com]
Craniofacial features include synophrys, arched eyebrows, long eyelashes, small upturned nose and thin downturned lips, small widely spaced teeth, and microcephaly. [asperbio.com]
- Dental Caries
Physical causes such as gastroesophageal reflux, dental caries, constipation, and other causes of pain should be ruled out. [medicalhomeportal.org]
Dental problems consist of delayed secondary tooth eruption, small or absent teeth, malposition, malocclusion, overcrowding of teeth, dental caries on the perilingual maxillary surface (due to gastro-oesophageal reflux disease (GERD)), periodontal disease [nature.com]
- Hearing Impairment
All patients with the classic form of the disease showed severe hearing impairments, whereas 4 patients without hearing impairments had the mild form. [ajnr.org]
OBJECTIVE: Cornelia de Lange syndrome (CdLS) is a multiple developmental disorder including hearing loss. The hearing impairment in CdLS patients is not only sensorineural but also conductive hearing loss (CHL). [ncbi.nlm.nih.gov]
[…] long philtrum micrognathia microbrachycephaly, microcephaly or brachycephaly upper limb malformations short 1st metacarpal oligodactyly acheiria micromelia growth restriction including intrauterine growth restriction intellectual disability hirsutism hearing [radiopaedia.org]
Hearing impairment can be difficult to diagnose and has been reported to improve with time in some adults. [orpha.net]
impairment Conductive deafness Conductive hearing loss [ more ] 0000405 Cryptorchidism Undescended testes Undescended testis [ more ] 0000028 Cutis marmorata 0000965 Elbow dislocation Dislocations of the elbows Elbow dislocations [ more ] 0003042 Failure [rarediseases.info.nih.gov]
There was a distinct facial dysmorphism with arched and bushy eyebrows, long philtrum, thin upper lip, depressed nasal bridge and hirsutism. [ncbi.nlm.nih.gov]
Face, Head & Neck
- Thin Lips
Symptoms Children with CdLS are born with distinct facial features characterized by long eyelashes, thin lips, typically thick eyebrows that join at midline, low set ears and upturned nose. [symptoma.com]
External examination showed a low hairline, synophrys, low-set ear, hypertrichosis, and smooth long philtrum with thin lips. The neck appeared short and broad. Finally, CdLS was diagnosed. [hindawi.com]
The syndrome carries a wide spectrum of clinical features which include: facial dysmorphism low set hairline in the front and back long eyelashes bushy eyebrows synophrys (unibrow) 15 upturned nose with anteverted nostrils thin lips with long philtrum [radiopaedia.org]
Craniofacial features consist of a clown-like appearance with large, low and curly eyelashes, micrognathia, thin lips and downturned upper lip (carp mouth), cleft lip and palate, optic atrophy, an upturned nose, and hirsutism. [whonamedit.com]
lips (94 percent of cases) Small lower jaw and/or protruding upper jaw (84 percent of cases) Cleft palate Other physical abnormalities which may or may not be present at birth include: Very small head (microcephaly) (98 percent of cases) Eye and vision [verywell.com]
- Psychomotor Retardation
Cornelia de Lange syndrome is a congenital disease, basically characterized by psychomotor retardation associated with a series of malformations, including mainly skeletal, craniofacial deformities together with gastrointestinal and cardiac malformations [ncbi.nlm.nih.gov]
Clinical progression leads to psychomotor retardation, language acquisition difficulties and, sometimes, behavioral disorders in the autistic spectrum. Hearing loss should be evaluated and monitored. [orpha.net]
KDM1A–related cleft palate, psychomotor retardation, and distinctive facial features is inherited in an autosomal dominant manner. [preventiongenetics.com]
- Behavior Problem
Under developed upper extremities Severe amount of body hair Hearing problems Low birth weight Small size of head Small stature Problems in vision Seizures Cleft palate Behavioral problem Self-injurious behavioral patterns Hearing defects Communication [symptoma.com]
In this study we describe a 23-year-old male patient with intellectual disability, behavioral problems, dysmorphic features, dysphagia, gastroesophageal reflux and skeletal abnormalities. [ncbi.nlm.nih.gov]
Because of problems with their mouths, hearing, and development, children with CDLS often begin speaking later than their peers. Behavioral problems for children with CDLS may include hyperactivity, self-injury, aggression, and sleep disturbance. [verywell.com]
- Global Developmental Delay
Physical findings: In children, classic CdLS is characterized by: • Early feeding difficulties; • Global developmental delays with severe to profound intellectual disabilities; • Limited language; • Poor growth; • Skeletal abnormalities involving missing [secure.ssa.gov]
Global developmental delay, in particular speech delay evolves towards intellectual disability ranging from mild to profound. [orpha.net]
KBG syndrome is characterized by macrodontia of central upper incisors, mental retardation, dysmorphic facial features, short statue, skeletal anomalies and global developmental delay, seizures, and intellectual disability. [preventiongenetics.com]
History revealed that patient had global developmental delay. Clinical examination Development Mental retardation, grossly delayed milestones, low pitched, weak, growling, cry in infancy. Craniofacial Cranium: Micro brachycephaly. [nijp.org]
Haiming Yuan, Lina Zhang, Mengfan Chen, Junping Zhu, Zhe Meng and Liyang Liang, A de novo triplication on 2q22.3 including the entire ZEB2 gene associated with global developmental delay, multiple congenital anomalies and behavioral abnormalities, Molecular [doi.org]
Prophylaxis should be taken not to use any anesthetic agent which may precipitate convulsions like ketamine. 7 Our patient did not present with such history but care was taken to prevent any episode of convulsion. [apicareonline.com]
History revealed that the child had low birthweight (1.75 kg), birth asphyxia, still birth, history of convulsions at 7 months, grossly delayed milestones and also demonstrated autistic and self-destructive tendencies. [nijp.org]
No single test can diagnose CdLS. A thorough physical examination would be done to carefully study for the signs and symptoms of the disease. In addition, X-ray and genetic testing are carried out to figure out the genetic mutations.
Imaging studies such as CT scan of the temporal bone need to be done to determine any abnormalities in the middle and inner ear. Hearing conduction tests must also be conducted because 90% of CdLS patients have an associated hearing disorder .
Ultrasound of the renal tract is also a necessity to understand abnormalities associated with the renal system. Echocardiography is also indicated in patients with CdLS to determine the cardiac functioning.
The major goal of treatment of CdLS is management of the symptoms to reduce discomfort associated with secondary anomalies. Treatment approach varies with age of the patient as the special needs of the child need to be catered to. This further means that a combined approach for correcting physical development and cognitive skills needs to be carried out.
Children with CdLS also suffer from various other associated disease conditions. Therefore appropriate treatment for each disease condition is also carried out.
Prognosis of the disease is usually unfavorable as affected children experience severe morbidity. Majority of the children die during the first few years of life. Those who survive these years have a short life span . Retrospective reviews on CdLS patients shows that respiratory symptoms are the major cause of death .
Complications of CdLS include the following:
- Disorders of the central nervous system
- Respiratory problems such as bronchopulmonary dysplasia
- Impaired renal function
- Cleft palate
- Lack of sensation of pain
- Intolerance to heat
- Cardiovascular diseases
The major factor that is known to play foul in the causation of Cornelia de Lange syndrome is genetic mutations . A total of 4 genes were found to be responsible for causing the congenital disorder.
Out of the 4 genes, the most common genetic mutation that gives rises to 50% cases of CdLS is the NIPBL gene on the chromosome 5. Gene SMC1A on the chromosome X and gene SMC3 on the chromosome 10 account for rest of the cases . The fourth gene known as HDAC8 on chromosome was discovered in the year 2012; however there is little evidence about the association of the gene with CdLS.
CdLS is not a heredity disorder and there are rare cases to prove that individuals living with such a syndrome would have children of their own.
The exact incidence of CdLS is not known. However, with the available data it can be concluded that 1 in every 10,000 to 30,000 develops CdLS.
Cornelia de Lange syndrome is a genetic disorder arising from mutation of multiple genes. During the early developmental years, mutations of the genes NIPBL, SMC1A, SMC3 and HDAC8 are known to trigger series of events that send across faulty information giving rise to unusual facial features, developmental delay, and underdeveloped upper extremities and feeding problems . Researchers have pointed towards the fact that 99% cases of CdLS are sporadic in nature.
Many cases of the disease can be prevented using prenatal diagnostic testing. Ultrasound examination during pregnancy can show intrauterine growth retardation. However, studies showed that about 68% of the cases of CdLS were not detected by this method. Therefore, proper examination during the second trimester for detection of few typical characteristics such as cystic hygroma, diaphragmatic hernia and right hand with 3 rays can provide information about CdLS. In addition, maternal serum testing for pregnancy associated plasma protein during the second trimester can also help in detecting CdLS.
Cornelia de Lange syndrome, abbreviated as CdLS is a congenital disorder causing developmental delay in children. This disorder is typically not diagnosed at birth and presents with severe physical and mental challenges.
CdLS was first described in the year 1933 by the scientist Cornelia de Lange . However, Brachmann also described characteristics similar to this disorder in the year 1916. Cornelia de Lange syndrome is characterized by behavioral problems, developmental delay, distinctive facial features, malformed upper extremities and growth deficiency. Genetic mutations are the major factor that gives rise to development of CdLS.
Cornelia de Lange syndrome (CdLS) is a congenital disorder characterized by slowed growth, poor development and unusual distinct facial features in affected children. Such a type of syndrome occurs due to genetic mutations. Affected children have a poor life expectancy as they are unable to survive the various associated disease conditions they suffer from. Children with CdLS also suffer from behavioral problems and have delayed cognitive development.
Cornelia de Lange syndrome occurs due to genetic mutations of 4 genes namely NIPBL, SMC1A, SMC3 and HDAC8. Researchers have also pointed towards the fact that about 99% cases of CdLS are sporadic in nature.
Children with CdLS are born with distinct facial features characterized by long eyelashes, thin lips, typically thick eyebrows that join at midline, low set ears and upturned nose. In addition, some of the other symptoms include presence of severe body hair, small head, small hands and feet, under developed upper extremities, vision impairment, hearing problems, seizures, feeding problems, heart abnormalities, hypoglastic genetalia and cleft palate.
Diagnosis of CdLS includes thorough physical examination of the signs and symptoms. In addition, genetic testing is carried out to study the genetic mutations. In addition, ultrasound of the renal tract and echocardiogram are necessary to study abnormalities of the kidneys and heart.
Treatment of CdLS includes management of the several disease conditions the child is suffering from. In addition, speech and behavioral therapy also forms a major part of the treatment regime.
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