Cornelia de lange syndrome

BACKGROUND: Cornelia de Lange syndrome (CDLS) is a rare multiple congenital anomaly syndrome characterized by a distinctive facial appearance, developmental delay, growth retardation, low birth weight, skeletal formation anomaly, and hirsutism. CASE: Here for the first time a case of CDLS from Iran, a 15-week-old male infant who was refereed as a case of multiple congenital anomalies. Clinical investigation showed that the child was a case of CDLS. CONCLUSION: This is the first case report with CDLS in Iran.


Introduction
Cornelia De Lange syndrome (CDLS) was first described by Cornelia de Lange, a Dutch pediatrician in 1933. [1]This syndrome is also called as Brachmann de Lange syndrome (BDLS) since he reported a patient with similar symptoms at autopsy in 1916. [2]cidence of this syndrome is variable, ranging from 1:10,000 to 1:100,000 live births in different population groups. [3]There is no racial predilection.It is slightly more common in females as compared to males (F/M: 1.3/1).
Most children with this syndrome could not live more than 2 years and the main cause of death was pneumonia along with cardiac, respiratory, and gastrointestinal abnormalities. [4]LS is a multisystem developmental disorder characterized by growth and developmental retardation, low birth weight, hirsutism, anomalies in the structure of the upper limbs, gastroesophageal dysfunction, ophthalmologic and genitourinary anomalies, congenital Address for Correspondence: Naeimeh Tayebi, Genetic part, Shahid Fiazbakhsh Rehabilitation Comprehensive Center, third Azadshar Square.E-mail: ntayebi@yahoo.com was normal.Both parents were normal and there was no history of deformity in their pedigree.
He was confi ned to bed during 18 days after birth because he had feeding problems and gavage feeding was done for him.
At presentation, the patient had confl uent eyebrows that appeared arched and well-defi ned and bushy, long curly eyelashes, low front and back hairlines, small nose with low bridge, turned-up nose, down-turned angles of the mouth and thin lips, long philtrum, highly arched palate, small lower jaw and protruding upper jaw, microcephaly [Figure 1A], to wide Anterior and posterior fontanelles, excessive body hair, Cutis marmorata, facial hypertrichosis, and malformed pinnas [Figure 1B, C].The patient had a low-pitched cry, umbilical hernia was seen when he cried, short neck, fi xed fl exion of both elbows [Figure 1 D,E].
An X-ray of right hand showed ulnar agenesis and monodactyl [Figure 1F], but the X-ray of left hand showed that both forearm bones were normal, but there were three fi ngers.His feet were not malformed.
Long coarse black hairs were present on the back associated with generalized hypertrichosis since birth.
The baseline blood, urine investigations and thyroid function tests were within normal limits.The cardiovascular, respiratory, brain computed tomography (CT) scan and ophthalmologic examination were described as normal.Ultrasonography of the abdomen did not reveal any organomegaly.
Examination of the genitalia showed bilateral undescended testis with hypospadiasis [Figure 1G].

Cytogenetic analysis
Peripheral blood from the patient was subjected to short-term culture in RPMI 1640 medium for 72 h.After metaphase arrests through exposure to Colcemide, cells were harvested, treated with hypotonic solution, and then fi xed with methanol and acetic acid according to standard procedures. [10]The harvested cells were dropped on clean slides and G-banding was done, and then stained with Wright's stain, for chromosome banding. [10]The clonality criteria and the karyotypic descriptions were according to the ISCN recommendations. [11]Analysis of 25 metaphase cells showed 46, XY in all cells.

Discussion
CDLS is relatively uncommon multiple congenital anomaly with unknown cause and recurrent risk.This syndrome may be the result of an inheritance metabolic error. [12]No environmental cause has been discovered.Although an autosomal dominant, autosomal recessive, and chromosomal anomaly have been suggested, most cases are sporadic. [13]agnosis of CDLS is dependent on the recognition of distinctive facial features, [14] in addition to the physical features as pre-and postnatal growth retardation, microcephaly, feeding problems, major malformations including limb defects, and characteristic facial features. [15]e to the characteristic facial features, the physiological Þ ndings, and the presence of a normal karyotype, the patient was diagnosed as CDLS. [16]ysiological Þ ndings to support the diagnosis were microcephaly, excessive body hair, short neck, ß exion of both elbows, absence of right ulna, malformed pinnas, and bilateral undescended testis with hypospadiasis.
Chromosomal analysis was performed to find out if there were chromosomal imbalances or gross rearrangement of the drosophilia nipped B gene (NIPBL) or SMC1L1 gene regions.The karyotype was normal.
Analyses for mutations in these genes are not currently available in Iran and there were no funds for testing abroad.Nonetheless, based on the clinical features, the present patient was believed to be the Þ rst CDLS case reported in the Iran.

Ellaithi et al. reported a case of BDLS from Sudan
for the Þ rst time.The patient was a 7-month-old female infant, who was refereed as a case of malnutrition.
Clinical investigation showed that the child was a classical case of BDLS. [17]m et al. evaluated ophthalmologic problems, for the Þ rst time, in a case of CDLS.They presented a case of CDLS in an 18-year-old female with a superÞ cial keratitis with entropion, ptosis, high myopia, lacrimal cutaneous Þ stula, and facial appearance. [18]1]

Conclusion
CDLS is a rare but well-characterized syndrome.
The key diagnostic features are the distinctive facial features, limb anomalies, and growth retardation.It is hoped that with the report of this case at the Genetic Research Center, Welfare organization, Yazd, Iran every attempt will be made to characterize "multiple congenital anomalies" that present to this center.

Figure 1 :
Figure 1: A 15-week-old male infant with Cornelia De Lange syndrome