Cornelia de Lange Syndrome: A Case Series from a Resource-Limited Country.

Cornelia de Lange syndrome is a rare genetic condition with developmental disorder and malformation affecting multiple systems. To describe the clinical and laboratory details and outcome of the children diagnosed with Cornelia de Lange syndrome, we retrospectively studied six cases who presented to our hospital between the years 2013 and 2015. Almost all had developmental retardation, with recurrent respiratory tract infections, and feeding difficulties. Synophrys with long curly eyelashes with low anterior and posterior hairline was present in all the children. Cornelia de Lange syndrome is a multisystem developmental disorder requiring interdisciplinary management. Symptomatic treatment generally given as therapy is very difficult. Early diagnosis and prompt management of associated disorder are useful for effective outcome of the disease.

INTRODUCTION

Cornelia de Lange syndrome (CdLS) is a rare genetic condition with developmental disorder and malformation affecting multiple systems. The clinical features vary widely among the affected individual, and the severity ranges from mild to severe. They present with typical craniofacial appearance, growth failure, intellectual disabilities, limb abnormalities, and hirsutism. A spectrum of phenotypic appearance is seen. The diagnosis is suspected based on the clinical findings and/or identification of mutation in one of the associated genes.[1] It affects both sexes equally with an estimated incidence of 1 in 10,000 live births with no racial predilection.[2] The etiology is still unknown, but mutation in the NIPBL gene located on chromosome 5 is considered to be responsible for the disease.[34] The disorder is present from birth, but it is not always diagnosed at birth. The diagnosis is made clinically through signs and symptoms observed by the clinician with detailed history, physical examination, and laboratory tests. Typical facial features include synophrys, highly arched eyebrows, long eyelashes, a short upturned nose, thin downturned lips, and micrognathia. We present a series of six patients that we saw in our hospital with varying clinical presentations.

CASES

This was a retrospective study of six cases who presented to our hospital between the years 2013 and 2015. The children were diagnosed based on the checklist provided by the CdLS foundation.[5] If these criteria were met, then the individual was diagnosed clinically with CdLS. Case records of all the patients were studied, and the clinical, physical, and laboratory parameters were taken. The following parameters were recorded: age at presentation, sex, family history, clinical features, laboratory findings, and course of the disease, treatment, and outcome. A written informed consent was obtained from the parents.

Of the six patients, four were male and two female. The age ranged from 7 to 120 months (median, 27 months). The average age at diagnosis was 15 months. Almost all had developmental retardation, with intelligent quotient below 70. Recurrent respiratory tract infections and feeding difficulties were seen in most of the patients. Synophrys with long curly eyelashes with low anterior and posterior hairline was present in all the children [Figure 1]. Intrauterine growth retardation was seen in three patients. One of the patients had seizure, which was controlled with antiepileptics. Some of them had hyperactivity with autistic behavior. Cardiovascular abnormalities, that is, ventricular septal defect (VSD) and atrial septal defect were seen [Table 1]. Chromosomal study was carried out in all the cases (4 XY, 2 XX).

Figure 1

Facial characteristics: Facial photograph of the child showing hirsutism, synophrys, depressed nasal bridge, upturned nose, long philtrum, and long curvy eyelashes

Table 1

Clinical, physical and laboratory features (n=6)

DISCUSSION

CdLS is a multisystem developmental disorder with the affected individual having varied range of clinical presentations from mild to severe. It is characterized from the beginning by intrauterine growth restriction, abnormalities of the skeletal system, developmental delays, and short stature.[1] They also have characteristic facial features such as synophrys, highly arched eyebrows, small and upturned nose, low-set ears, and micrognathia; and most of them have upper limb abnormalities, hirsutism, and mental retardation. Radiographic examination can be helpful in the diagnosis of limb abnormalities. Due to the wide clinical presentation, sometimes it can be difficult to ascertain the diagnosis; hence genetic testing, if available, can aid in the diagnosis.

Most of the children had recurrent respiratory tract infection, which was attributed to feeding difficulties.

Sommer[6] reported gastroesophageal reflux as a common comorbidity associated with these children, which with early recognition and appropriate management can lead to improved lifestyle.

Berney et al.[7] correlated the degree of mental retardation and behavioral phenotypes such as hyperactivity, self-injurious behavior, and autistic-like syndromes, which was also observed in our patients. Developmental delay and mental retardation were present in majority of the cases. Upper limb abnormalities such as soft tissue syndactyly, polydactyly, and micromelia were observed. Jackson et al.[8] reported upper limb deficiencies in only 27% of the cases, whereas growth retardation in all of the cases. Cardiovascular disorders such as VSD were seen in three of our cases, with similar reports from other studies.[89]

Genetic studies for mutation analysis were not performed in our patients; hence, the dominant mutation profile could not be showed.

CONCLUSION

Although studies have been published on these disorders, we would like to share our experience of the diagnosis based on the checklist provided by the CdLS foundation, its management, and follow-up of these patients who are doing quite well with multidisciplinary therapy. Early diagnosis and prompt initiation of supportive therapy would improve the outcomes of these children.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.