Cornelia de lange syndrome

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  • Indian J. Pediat. 37 : 1 52, 1970

    CORNELIA DE LANGE SYNDROME*

    Report of a Case

    ISHWAR C. VERMA

    New Delhi

    In 1953 Cornelia de Lange from Amsterdam described two infants with mental retardation, a distinctive facies (a small nose, anteverted nostrils and eyebrows that meet in the mid- line ) and multiple minor defects. Earlier in 1916, Braclunann had des- cribed a case of symmetrical mono- dactyly with ulnar defect, ,h ebbing of the an'ecubital fossae and other anomalies including dwarfism and hirsutism. Hence the syndrome is often called Brachmann-de Lange syndrome (Optiz et al 1965). McArthur and Edwards (1967), sug- gest that the eponym Brachrnann be restricted to those cases with severe bilateral arm defects, while the eponym de Lange be applied to cases with other features of the syndrome.

    The syndrome is by no means rare, 144 cases having been reported (Pashayan et al 1969). No cases have been documented in the Indian medical literature so far. (gee Ingle and Mali, this issue). This report presents an additional typical case of the de Lange syndrome.

    Report of Case

    A.B., a 13-month-old boy was referred to the All India Institute of

    *From the Department of Pediatric.s, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-I 6.

    Medical Sciences Hospital, for evalua- tion of failure to thrive. He was the third child of unrelated parents, the other sibs being normal. The gestation was complicated by fever lasting two days at five months ar.d leakage of amniotic fluid at eight months. He was born after an 8~- month pregnancy with a weight of 1.6 kg. The delivery was uncompli- cated but he had to be fed by gavage tube for 3 days and then given artificial feeds. He smiled at five months, held his head on being lifted at six months, and since 10 months could only sit with support. He had two severe attacks or bronchopneum- onia at the age of 3 months and 1 year.

    On examination at 13 months, he weighed 5.2 kg. His crown heel length was 57 cm, head circumference 38.5 cm. and biparietal diameter 12 cm. His head was brachycephalic, the bone along 1he coronal suture being raised. The forehead was prominent, the hairline was low while the eyelashes were bushy and meeting in the midline. The ears were low- set while the eyes had a mongo- loid slant. The face was grotesque, with a fiat bridge of the nose and anteverted nares. The upper lip was long and thin. The teeth were unerruptcd. The neck was short but there was no webbing. The chest showed a depression over the left

  • VERMA--CORNELIA DE LANGE SYNDROME 153

    lower costal area. There wasa grade 3 systolic murmur at the lower left sternal area, with a mild cardiae enlargement. The liver was just pal- pable while the spleen was not palpa- ble. There was a capillary heman- gi0ma on the abdominal wall and another one on the thigh. There was fine hair all over the back nnd shoulders. There was a left inguinal hernia while the genitalia were nor- mal. Both the elbows had flexion contractures. The hands had short metacarpals while the fing~rs app:ared long. The thumb was proximal- ly placed. There was bilateral syndactyly of the 2nd and 3rd toes. Investigation revealed hemoglobin to

    be 10 G. ~, total and differential leuco- cyte count~, routine urinalysis and urinary aminoacid chromaf, ogram were normal. Orthotoluidine blue spot test for mucopolysaccharidosis was negative. Protein bound iodine was 5.3 ugH. X-rays of the skull showed micro-brachycephaly, of the chest transversely disposed ribs, and of the wrists the nondevelopment of any epiphysis with a short first meta- carpal. Dermatog!yphics showed whorls on the I st, 2nd, 4th and 5th digits and an ulnar loop on the third digit of the right hand, hand, with ulnar loops on the 1st, 2nd and 3rd digits and whor l on the 4th and 5th digits of the left hand. The axial triradius was proximal with radial loops on the hypothenar eminence bilaterally. There was a simian crease on the right hand. The soles showed bilateral tibial loops on the hallucal area. Chromosomal analysis showed a normal karyotype (46, XY).

    At the age of 15 months the child

    expired at home after an attack of bronchopneumonia.

    Discussion

    This syndrome is so characteristic that once a case has been seen another may be identified immediately. Infants with this syndrome have the most striking resemblance to one another (Ptaceket al. 1963). Thischild hadall the typical features--primordial growth retardation, mental retardation, micro- brachycephaly, synophris (bushy eyebrows meeting in the midline), small nose, anteverted nostrils, genera- lized hirsutism, flexion contractures of the elbows, simian crease, proximally placzd thumbs and syndaetyly of the 2nd and 3rd toes. In addition, he had congenital heart disease and capillary hemangiomas. He showed a severe mental retardation like the majority of the cases reported (Jarvis and Stimson 1963, McArthur and Edwards 1967). Recently, however, Pashyan etal. (1969), reported 3 eases with characteristic clinical and radio- logical features but without severe mental retardation. Roentgenolo- gically the present ease showed microbrachycephaly, abnormal meta- carpal bones, delayed appearance of the epiphyseal centres, and horizon- tally placed ribs. Other distinctive features described by Lee and Kenny (1967) are hypoplasia of the first metacarpal, clinodactyly of the fifth finger, hypoplasia, and subluxation of the radial head, a flat acetabular angle and a deformed sternum wiih fewer than normal epiphyseal centres. This case had repeated lower respira- tory tract infections. Ptacek etal. (1963) reported lower gamma globulin levels in the blood although Schle-

  • 154 INDIAN JOURNAL OF PEDIATRICS VOL. 37 NO. 267

    singer et aL (1963) did not find any lack of gamma globulins. They reported defective functioning of the anterior pituitary with secondary effects on other endocrine glands and suggested that the inability of these patients to withstand infections poorly may be due to lack of adrenal func- tion. Chromosomal studies in this case were normal as in the majority of reported cases. Some authors have described abnormal karyotypes but with no consistent abnormality (Payne and Meeda 1965, Falek etat. 1966, Brocholm etal. 1968, Eeg-O'.ofson and Hall 1968). Dermatoglyphic patterns in this ease showed a simian crease, and radial loops on the hypothenar eminence, with bilateral tibial loops in the hallucal area. In the absence of dermatoglyphic studies in other reported cases the significance of these findings is not clear. The etiology of the syndrome is unknown. An incom- plete and to some extent faulty differentiation accounts for most of the morphological abnormalities. There is a striking delay in maturation of the structure and function of most organ systems. An autosomal recessive mode of inheritance has been suggested (Opitz and Smith 1966) although Pashayan et al. (1969) reject this hypothesis after a genetic analysis of 54 families, comcluding that the syndrome is familial. They have calculated an empirical risk of recur- rence in siblings of affected infants as 2-5%.

    Summary

    A 13-month-old boy having typical features of Cornelia de Lange syndrome is described. Two additional features were capillary hemangiomata and abnormal dermatoglyphie patterns.

    He had repeated lower respiratory tract infections and succumbed at the age of 15 months to broncho- pneumonia.

    I am thankful to Dr. O.P. Ghai, Professor and Head of the Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, for his encouragement and permission to publish this case. 14o photograph is appended as the parents refused permi~ion for the child to be photographed.

    References

    Brachmann, W. (1916). Qaoted by Optis et al. (1965).

    Brochelm,K.A., Eeg-Ologason, O. and Hall, B. (1968). An inherited chromosomal aberra- tion in a girl with signs of de Lange syndrome. Casereport. Acta Paediat. Scand. 57, 547.

    Falek, A., Schmidt, R. and Jervis, G.S. (1966). Familial de Lange syndrome with chromosomal anomalies. Pediatric~ 37, 92.

    Jarvis, G.A. and Stimson, C.W. (1963). De Lange syndrome. J. Pediat. 63, 634.

    de Lange, C. (1933). Sur un type nouveau de degeneration (typus amstelodamcnsis). Arch. de med d enf . 36, 713.

    Lee, F.A. and Kenny, F.M. (1967). Skeletal changes in the Cornelia de Lange syndrome. Amer..L Roentgenol. 100, 27.

    McArthur, R.G. and Edwards, A.J.H, (1967). de Lange syndrome : report of 20 cases. Canad. Meal. Ass. J. 96, 1185.

    Optiz, J.M., Segai, A.T., Lehrke, R.L. and Nadler, H.L. (1965). The etiology of the Brachmann-de Lange syndrome. In Birth Defects. National Foundation, New York 163, 65.

    Pashyan, H., Whelan, D., Guttman, S. and Fraser, F,C. (1969). Variability of the Lange syndrome : report of 3 cases and genetic analysis of 54 families. J. Pediat. 75,853.

    Payne, H.W. and Maeda, W.K. (1965). The Cornelia de Lange syndrome. Clinical and eyt0- genetic interpretation. Canad. Med. ,4.J. 93, 577.

    Ptacek, L.S. Optiz, J.M. Smith, D.W. Gerrit- sen, T. and Waisman, M.A. (1963). The Cornelia de Lange syndrome. J. Pediat. 63, 1000.

    Schlesinger, B., Clayton, B., Bodian,M. and Vernon Jones (1963). Typus degenerativus Amstelodamensis. Arch. Dis. Childh. 38, 349.