American Journal of Medical Genetics 4 9 137-138 (1994)

Letter to the Editor

VACTERL With Hydrocephalus: A Further Case With Probable Autosomal Recessive Inheritance

To the Editor:

In a previous paper on VATERNACTERL association [Corsello et al., 19921, we reported 9 cases observed over a period of 6 years. None of them showed hydrocephalus or central nervous system (CNS) malformations and none exhibited a mendelian mode of inheritance. We now report on a further VACTERL case with hydro- cephalus, occipital encephalocele, and probable autoso- ma1 recessive inheritance.

CLINICAL REPORT The male child was born to consanguineous parents

(first cousins) at term of their first pregnancy. Delivery was spontaneous; birth weight was 1,590 g and birth length 40 cm. Family history was unremarkable. Intra- uterine growth retardation and multiple congenital ab- normalities were noted on ultrasounds in the third tri- mester of gestation. At birth, occipital encephalocele, bilateral cleft of the hard and soft palate, hypoplasia of both forearms with aplasia of the 1st and 2nd finger bilaterally, undescended testes, and imperforate anus were noted.

X-rays showed severe hypoplasia of radius and ulna as well as aplasia of the 1st and 2nd digital ray bilaterally, sagittal clefting of the thoracic vertebrae, aplasia of occiput. Brain ultrasound scan showed dilatation of lat- eral ventricles and aplasia of corpus callosum. Abdomi- nal ultrasound showed right kidney aplasia. Chromo- somes obtained from peripheral blood were normal (46,XY); no spontaneous increase of chromosome break- ages was noted. The child died 4 hours after birth due to cardiac and respiratory failure.

At autopsy, the following defects were found: occipital encephalocele with protrusion of cerebellum, hydro- cephalus with anterior dilatation of the lateral ventri- cles, bilateral clefting of the hard and soft palate, oesophageal atresia with lower tracheo-oesophageal fistula, anal atresia with recto-urethral fusion, kidneys fused on the left side, the right ureter implanted into the bladder across the midline, atrial and ventricular septa1

Received for publication May 3, 1993; revision received July 2, 1993.

Address reprint requests to Giovanni Corsello, Cattedra di Patologia Neonatale IMI, Universita di Palermo, Via Cardinale Rampolla, 1, 90142 Palermo, Italy.

defects (posterior perimembranous VSD), severe hypo- plasia of radius, and ulna with absence of the thumb and 2nd finger bilaterally.

DISCUSSION VACTERL with hydrocephalus is now considered a

distinct genetic entity. Instances of autosomal recessive as well as X-linked recessive inheritance have been re- ported [Sujansky and Leonard, 1983; Briard et al., 1984; Hunter and MacMurray, 1987; Evans et al., 1989; Iafolla et al., 1991; Sorge et al., 1992; Genuardi et al., 19931.

The present report helps to expand the phenotype of the syndrome, adding new findings such as cleft of pal- ate and severe upper limb reduction defects. High peri- natal lethality of this syndrome is related to the severe CNS abnormalities such as occipital encephalocele. Nor- mal karyotype and the absence of spontaneous chromo- some breakages and rearrangements, recently found in 2 newborns apparently showing VACTERL with hy- drocephalus [Porteous et al., 19921, excluded Fanconi anemia.

Parental consanguinity of the present case strongly supports autosomal recessive inheritance. Careful ul- trasonographic evaluation of the fetus is indicated in future pregnancies.

We think that the brain and skull must be carefully evaluated in all VACTERL newborns because CNS mal- formations, which are very rare in the truly sporadic cases of this association, constitute a specific diagnostic marker of familial cases. On the other hand, all new- borns with congenital hydrocephalus should be thor- oughly studied to search for additional congenital ab- normalities included in the VACTERL association.

REFERENCES Briard ML, Le Merrer M, Plauchu H (1984): Association VACTERL and

hydrocephalie: Une nouvelle entiti, familiale. Ann Genet 27: 220-223.

Corsello G, Maresi E, Corrao AM, Dimita U, Lo Cascio M, Cammarata M, Giuffre L (1992): Brief clinical report VATERNACTERL asso- ciation: Clinical variability and expanding phenotype including laryngeal stenosis. Am J Med Genet 443313415.

Evans JA, Strane LC, Kaplan P, Hunter AGW (1989): VACTERL with hydrocephalus: Further delineation of the syndrome(s). Am J Med Genet 34:177-182.

Genuardi M, Neri G, Chiurazzi P, Capelli A (1993): X-linked VACTERL with hydrocephalus: The VACTERL-H Syndrome. In Opitz JM (ed): “Blastogenesis: Normal and abnormal.” New York John Wiley and Sons, Inc., for the National Foundation-March of Dimes, BD:OAS XXIX:227-233.

0 1994 Wiley-Liss, Inc.

138 Corsello and Giuffr6

Hunter AGW, MacMurray B (1987): Malformations of the VATER association plus hydrocephalus in a male infant and his maternal uncle. Roc Greenwood Genet Cntr 6:146-147.

Sujansky E, Leonard B (1983): VACTERL association with hydro- cephalus-A new recessive entity? Am J Hum Genet 35:119A.

Iafolla AK, McConkie-Rose11 A, Tsong Chen Y (1991): VATER and hydrocephalus: Distinct syndrome? Am J Med Genet 38:46-51.

Porteous MEM, Cross I, Burn J (1992): VACTERL with hydrocephalus: One end of the Fanconi Anemia spectrum of anomalies?. Am J Med Genet 43:1032-1034.

Sorge G, Romeo MG, Distefano G, Cocuzza M, Incorpora G (1992): Associazione idrocefalo-VATER in un neonato pretermine. Riv Ital Pediatr 18:469-471.

Giovanni Corsello Liborio GiuffrZ! Cattedra di Patologia Neonatale IMI Universita di Palermo Palermo, Italy