Spectrum of Cornelia de Lange | Annals of Pediatrics

Classic CdLS, recognized at birth, is characterized by a physical phenotype with characteristic craniofacial features, pre- and postnatal growth retardation, limb reduction defects (mainly upper limbs), hirsutism, and psychomotor developmental delay/mental retardation. Abnormalities in various systems are common: gastroesophageal reflux (the most common and important medical complication in patients with CdLS), sensorineural hearing loss, congenital heart defects, kidney and genital abnormalities, and others.3.4.

characteristic craniofacial features include microcephaly with brachycephaly, synophrenia, thick arched eyebrows, long eyelashes, a short nose with a sunken bridge and everted nostrils, an elongated filter with a thin upper lip, and retrognathia.3.4 (Figure 1 and Table 1).

He stunting This is a very common disease that occurs in utero. Patients present with generalized and symmetrical microsomia, which results in low weight, short stature, and microcephaly that persist into adulthood.5.6. All this led to the development of specific schemes for the syndrome.7. Although growth hormone levels are usually normal, some patients with low levels have been treated with this hormone.8.9.

He psychomotor retardation/mental retardation present in most patients with classic CdLS and is usually severe/deep10. Absence or delay of speech is commonly associated with autism spectrum disorders and behavior disorders. From a neurological perspective, patients may present with epilepsy, motor (stereotypical movements) and sensory disturbances (decreased sensitivity to pain or intolerance to cold or heat), hypotension, or sleep problems. Recently, damage to the autonomic nervous system has also been described in small fiber neuropathy, sometimes accompanied by asymmetry of sympathetic responses in the lower extremities.eleven.

limb abnormalities They occur in approximately 80% of cases. 25 to 30% have severe malformations, mainly reduction defects of the upper limbs such as monodactyly or oligodactyly, while the remainder typically have small hands and feet, which may be accompanied by minor malformations such as distally set thumbs or clinodactyly. These abnormalities are usually bilateral and usually asymmetrical.12 (Fig. 1, Table 1).

He gastroesophageal reflux (GER) is the main medical problem in classic CdLS and affects 93.3% of patients.13.14. It should be assessed from an early age in all patients with nutritional problems by performing pH/manometry or, failing that, an upper gastrointestinal barium contrast study. In the absence of adequate treatment (see section “Treatment and observation”), this can lead to complications such as esophagitis, aspiration pneumonia/pneumonia and changes in behavior (irritability, self-aggression, etc.), which are often ineffectively treated with psychotropic drugs. drugs.

Other digestive abnormalities that are much less common include intestinal malrotation (2-3% of cases), which should always be kept in mind in patients with CdLS presenting to the emergency department with acute abdominal pain, pyloric stenosis (7%) or congenital diaphragmatic herniafifteen.

In the sensory area, the most common complication is Sensorineural hearing losspresent in 80% of patients, of whom almost half have profound bilateral hearing loss.16. In the ophthalmological field eyelid ptosisusually bilateral, and myopia (>50% of cases) and nystagmus (40%). Less common are tear duct stenosis, strabismus, microcornea, glaucoma, or optic nerve coloboma.17.

From the cardiovascular system, about a third of patients have Congenital heart defectThe most common anomalies are ventricular or atrial septal defects, pulmonary stenosis, tetralogy of Fallot, hypoplastic left heart syndrome, and bicuspid aortic valve.18.

A recent study showed that some people may have early cardiomyopathy, which can be detected using the speckle tracking even before the onset of clinical symptoms and changes in other echocardiographic or analytical parameters19.

In the genitourinary system cryptorchidism in men (75%), bicornuate uterus in women (25%) and genital hypoplasia in both sexes (50%). Renal anomalies are rare, the most common being vesicoureteral reflux.twenty (10%) (Table 1).

Some endocrine dysregulation has also been described, with changes in prolactin levels and delayed puberty. Change in some patients Homeostatic model for assessing insulin resistance (HOMA-IR) is associated with the early development of insulin resistance.9. In addition, low levels of muscle mass and bone density have been described.twenty one.

Other less common clinical manifestations include cleft palate, dental abnormalities, marbled skin, and soft crying.3 (hoarsely).

Patients with classic CdLS are usually diagnosed at birth, so appropriate therapeutic measures can be started early, mainly in the area of ​​feeding, often involving the use of a nasogastric tube or even gastrostomy, which may be necessary. in the first months or years of life. It is important to keep in mind that patients with classic CdLS are usually born and grow at percentiles below normal limits, and therefore the pediatrician should not insist on overfeeding them, which will worsen the GER that affects most. It is therefore advisable to use your own syndrome growth charts (available at: https://www.corneliadelange.es/). The most common complications throughout life are pneumonia/pneumonitis due to aspiration of gastric juice (due to GER), which is one of the main causes of early mortality.14 (31% of deaths), intestinal obstruction (due to volvulus due to intestinal malrotation) (19%), caused by serious congenital malformations (diaphragmatic hernia or congenital heart disease) (15%). Other causes of early mortality were neurological complications and accidents (8%) and sepsis (4%).

In addition to classical CdLS, due to advances in genetic diagnosis, other “non-classical” CdLS phenotypes have been identified over the past two decades, typically milder ones that are typically difficult to diagnose by pediatricians. Due to the large clinical variability of patients with these forms, some authors prefer to use the term “Cornelia de Lange spectrum” (CdL) instead of CdLS.

In general, patients with “non-classical” forms tend to have a less characteristic phenotype (less pronounced signs) than classic patients with synophredia and gestalt facial (Fig. 1).