Ingrid Witters, MD*; Philippe Moerman, MD**; Jean-Pierre Fryns, MD*.

*  Center for Human Genetics, University of Leuven, Leuven, Belgium;
** Department of Pathology, University of Leuven, Leuven, Belgium.

There are no potential conflicts (financial or personal) with regard to to this article.
This case-report is in approval with the ethical recommendations of the University Hospital Leuven.

Case report

A primigravida was referred for polyhydramnios at 28 weeks. Ultrasound revealed an overt polyhydramnios (AFI: 49 cm), fetal mild ventriculomegaly (atria:11 mm), absent stomach filling, camptodactyly of fingers and toes and no fetal movement.

After amniotic fluid drainage, fetal movements remained absent and because the prognosis seemed unfavourable an induction of labor was performed at 29 weeks with the birth of a stillborn girl (weight: 1180 g, head circumference: 26.6 cm, length: 40 cm).

Macroscopic evaluation revealed trigonocephaly with a prominent metopic suture, facial dysmorphy with narrow palpebral fissures, a long philtrum, a small mouth with micrognathia and small ears (Figure 1a-b). She had long toes and fingers with camptodactyly (Figure 2a-b).

Internal examination further showed a proximal oesophageal atresia with a distal tracheo-esophageal fistula, incomplete intestinal rotation, a Meckel’s diverticle, incomplete lung lobation, a bicuspid dysplastic pulmonary valve, a uterus didelphys with a vaginal septum with normal ovaria.

The karyotype from amniotic fluid cells showed a 9p deletion/distal 15q duplication, as an unbalanced result of a paternal translocation t(9;15)(p22;q24). The final dysmorphism in the present patient was typical for a 9p distal deletion syndrome.

The chromosome 9p deletion was initially characterised in 1973 by Alfi et al., who reported a characteristic phenotype observed in six patients (Alfi et al., 1973) (monosomy 9p-syndrome: MIM158170).
The clinical features of the 9p-deletion syndrome include mental retardation and dysmorphic facial features (trigonocephaly, midface hypoplasia, upward-slanting palpebral fissures, and a long philtrum ) (Huret et al., 1988).
Other frequently observed features include hypertelorism, epicanthus, small palpebral fissures, flat nasal bridge, anteverted nares, low-set posteriorly angulated ears, microstomia, micrognathia, short-neck, widely spaced nipples, long fingers and toes due to elongation of the second phalanx, flat feet and hypotonia.
Malformations less frequently seen with 9p- deletion include cardiac defects, hernias, omphalocele, choanal atresia, abnormal genitalia and scoliosis (Breg et al., 1976; Huret et al., 1988; Taylor et al., 1991; Bennett et al., 1993; Teebi et al., 1993; Shashi et al., 1994).
Huret et al. (1988) reviewed 80 cases with deletions of 9p and found that approximately half were due to de novo deletions and the remaining half due to unbalanced rearrangements and that death, due to gross visceral malformations, occurred more often in cases of del(9p)with another unbalanced chromosome segment.
With conventional banding, breakpoints in monosomy 9p syndrome range from 9p21 to 9p24, with the majority at 9p22 (Christ et al., 1999).
Kawara et al. (2006) described a boy with characteristics of monosomy 9p syndrome and narrowed from his data and previous studies the shortest region of overlap in the syndrome to a 4.7-Mb segment at 9p22.2-p23.
In 46XY patients with terminal deletions of 9p, male to female sex reversal has been reported with a critical region for sex-reversal localized to 9p24.1 (Calvari et al., 2000).

The present child with features typical for 9 p deletion syndrome also has a proximal oesophageal atresia which was most likely the cause of the acute polyhydramnios. As far as we know, the oesophageal atresia and the uterine malformation have been described neither in 9p distal deletions, nor in distal 15q duplication.

In general distal 15q duplications are not associated with specific dysmorphism nor distinct associated malformations (Chandler et al., 1997). Interestingly, the 9p deletion had the largest impact on the phenotypic of the present malformed female child.

References 

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