Cornelia de-Lange syndrome (CdLS), also known as Brachmann de-Lange syndrome, comprises of congenital malformations, growth retardation, and neurodevelopmental delay [1-8].The diagnosis of CdLS is usually done after birth, but the syndrome could be suspected after the first trimester of pregnancy by ultrasonography [9-16]. Avagliano et al [17]. Proposed that following a sequence of detailed scans and examinations, CdLS-affected fetuses could be diagnosed in utero, when one or more characteristics, such as fetal growth rate, limb defects, facial abnormalities, diaphragmatic hernia, and heart diseases. A combination of signs and symptoms defines the classic CdLS phenotype [18]. The cardinal features of CdLS are synophrys, short nose, concave nasal ridge and/or upturned nasal tip, long and/or smooth philtrum, thin upper lip vermilion, downturned corners of the mouth, hand oligodactyly and/or adactyly, congenital diaphragmatic hernia. CdLS maybe associated with global developmental delay and/or intellectual disability, prenatal growth retardation, postnatal growth retardation, microcephaly (prenatally and/or postnatally), small hands and/or feet, short fifth finger and hirsutism [18]. A gene responsible for CdLS–NIPBL on chromosome 5–was discovered in 2004 by researchers at Children's Hospital of Philadelphia. In 2006, a second gene–SMC1A on the X chromosome–was found by Italian scientists. A third gene discovery was announced in 2007 [19]. The gene SMC3 is on chromosome 10 and was also discovered by the research team in Philadelphia. The latter two genes seem to correlate with a milder form of the syndrome. The vast majority of cases are due to spontaneous mutations, although the defected gene can be inherited from either parent, making it autosomal dominant. The types of mutations seen in CdLS rarely include large deletions and 50% have detectable point mutations (frameshift, splice site, nonsense, and missense) [20].

We report a case of a 5-year-old boy, born of a non-consanguineous marriage, second by birth order, presented with generalized tonic-clonic epilepsy since 3 years of age. There was a history of developmental delay and poor performance at school. His birth history was uneventful with a low birth weight of 2.2 kg.

Fig-3: Clinodactyly

NIPBL is known to regulate cortical neuron migration in mice [25] and, indeed, cortical malformations have been described in individuals with CdLS caused by NIPBL variants [26], as have small callosal bodies, white matter abnormalities, cerebellar anomalies, and brainstem abnormalities. Individuals with CdLS may have specific deficits in executive function beyond what is expected given the level of intellectual disability, especially in mental flexibility and visual short-term memory [27]. Hence, evaluating their cognitive strengths and weaknesses and structuring their environment accordingly is of utmost importance. In a study of 42 individuals with NIPBL variants, a (fairly weak) positive correlation was observed between chronological age and behavioral difficulties [28], and statisticallysignificant correlations were found between chronological age and measures of interest and pleasure, and insistence on sameness [29], indicating older individuals exhibit more difficulties. Parents should be counseled about prenatal diagnosis in the subsequent pregnancy. Prenatal molecular testing can be performed on samples obtained from chorionic villous sampling or amniocentesis or by testing embryonic cells obtained through in vitro fertilization [18]. The major indications for prenatal diagnostics are an earlier child with CdLS, a new pregnancy in a family with a known genetic alteration in a CdLS gene, or, as occurs most frequently, no family history but features suggestive of CdLS on fetal ultrasonography [18]. They usually have a vast range of health problems, making it important for the pediatrician to be aware of the child's special needs. The multidisciplinary treatment approach is the key to success in managing children with CdLS.