Roberts syndrome with cystic hygroma: a rare clinical presentation of a rare syndrome

Description

We had an opportunity to witness this rare case in the Women’s Wellness and Research Center, Qatar. The mother is in her late ‘20 s’, gravida 3 para 2, with a history of previous vaginal deliveries and no significant medical conditions. She conceived spontaneously after a consanguineous marriage of second-degree consanguinity. Her previous two siblings are normal. Her family history is positive for congenital anomalies and intrauterine fetal demise.

Her 13 week scan showed a nuchal translucency (NT) measurement of 2.7 mm with cystic hygroma. A detailed fetal anatomy scan in the fetomaternal unit revealed multiple congenital anomalies, including non-immune hydrops fetalis, a large cystic hygroma with generalised skin oedema, bilateral pleural effusions, small lung volume with possible lung hypoplasia, kyphoscoliosis, possible sacral agenesis and polyhydramniosfigure 1. Amniocentesis was performed, yielding a normal karyotype and microarray result. A multidisciplinary team, including specialists from genetics, fetal medicine, obstetrics and neonatology, was involved in the antenatal care and counselled the parents regarding the poor prognosis and the possibility of intrauterine demise.

Figure 1. Various prenatal ultrasound images showing anatomical abnormalities with a large cystic hygroma. (A) Viable pregnancy with a huge cystic hygroma with septation. (B) Axial view of the fetal head in the transthalamic plane, showing multiseptated cervicoccipital cyst. (C) Polyhydramnios. (D) The image shows fetal foot suspension of bilateral clubfeet. (E) Longitudinal view of fetal spine shows hemivertebra. (F) Axial view of the fetal head shows cystic hygroma with multiple thin septations.

The mother was initially planned by the obstetric team for vaginal delivery based on her previous two vaginal deliveries. At the gestational age of 34 weeks, the baby was delivered by elective lower-segment caesarean section due to severe polyhydramnios, non-immune hydrops and huge cystic hygroma. The baby was non-vigorous, with a heart rate of <100 beats per minute and no spontaneous breathing. The baby was declared dead at the age of 30 min. The diagnosis of Roberts syndrome was highly suspected by clinical features. A clinical examination revealed a hydrops fetalis, large cystic hygroma, hypertelorism, beaked nose, premaxillary protrusion, ear malformations, micrognathia, fused neck, bilateral tetra-phocomelia, thumb aplasia, syndactyly, elbow and knee flexion contractures, and fused genitalia. Figures24 show the anterior, lateral and posterior views of the baby, respectively. Skeletal survey showed kyphoscoliosis of the lumbosacral spine and bilateral upper limb deformities with excess soft tissue in the neck, as shown in figure 5. The parents declined autopsy and testing for the specific gene for Roberts syndrome for both the baby and parents due to its high cost.

Figure 2. Anterior view of the baby.

Figure 4. Posterior view of the baby.

Figure 5. Skeletal survey of the baby.

Figure 3. Lateral view of the baby.

Roberts syndrome, also known as pseudothalidomide or SC-phocomelia, is a rare genetic disorder with 150 cases reported worldwide currently. It is a rare autosomal recessive genetic disorder, named after John Roberts, who reported the case of a male infant with bilateral cleft lip and tetraphocomelia. The syndrome is inherited from two copies of the mutated gene from both parents. The diagnosis can be suspected clinically based on its characteristic craniofacial and limb deformities, both pre- and post-natally. The main clinical features are growth retardation, craniofacial abnormalities and limb malformations. Craniofacial features include microcephaly, dolichocephaly, micrognathia, premaxillary prominence, microbrachycephaly, downward-slanted palpebral fissures, widely spaced eyes, exophthalmos, corneal clouding, cleft palate and ear malformations. Limb deformities include bi-/tetraphocomelia, hypomelia, oligodactyly with thumb aplasia, syndactyly and clinodactyly, with more severe manifestations observed in the upper limbs.^{1 2} In addition, cardiovascular system anomalies, including atrial septal defect, ventricular septal defect or patent ductus arteriosus and renal anomalies, including polycystic or horseshoe kidney, might be seen in patients with Roberts syndrome.³

According to Abbas et al, two geneticists of Colombian origin discovered the ESCO2 gene mutation located at 8p21.2, which is responsible for Roberts syndrome.⁴ Almeida et al also described a Brazilian study that dealt with the Roberts syndrome population and concluded replicating patterns of homologous alphoid centromeric DNA for 9, 11, 16 and 17 chromosomes with fluorescence in situ hybridisation analysis.⁵ However, there are no genotype or phenotype specifications established.¹ Another notable description in the literature is the ‘rail-road track’ appearance of chromosomes, which is referred to as premature centromere separation and is a major diagnostic marker.²

Babies with the syndrome are recorded to have birth lengths less than 37 cm, but those with more than 37 cm and fewer deformities tend to show better outcomes. One of the case reports described a child who survived until the age of 5 years of age, although most of the cases do not survive beyond infancy.⁶ Management of the survivors includes a holistic approach involving plastic surgeons, paediatricians, orthopaedics, physiotherapists, speech therapists, cardiologists, nephrologists, eye specialists, social workers and genetic counsellors to improve the quality of life and palliative care with all the possible corrections.³ A recurrence risk of 25% has been identified in couples with a positive family background, and it is recommended for them to conduct prenatal diagnosis using imaging and genetic modalities, and also propose to them a possible preimplantation diagnosis. Cytogenetic testing for Roberts syndrome remains the gold standard for diagnosis.7,9 The lack of genetic study in our patient and both parents is a significant gap in our case.

Cystic hygroma is a type of lymphangioma, which is a vascular anomaly associated with lymphatic malformations. It is formed by fluid accumulation, mainly located at the cervicofacial and axillary regions. Cystic hygroma is mostly located in the neck (75%), followed by the axilla (20%), the retroperitoneum and intra-abdominal organs (2%), the limbs and bones (2%) and the mediastinum (1%). It is often associated with chromosomal aneuploidies, hydrops fetalis and intrauterine fetal death. Its incidence is also increased in patients with multiple pterygium syndrome, Roberts syndrome, Noonan syndrome, Beckwith-Wiedemann syndrome and Proteus syndrome. Its prognosis depends on the presence of chromosome abnormalities, hydrops fetalis, septations within the lesion, lesions with thick walls and its association with other major malformations.^{9 10}

In conclusion, Roberts syndrome is a rare disorder that can be diagnosed clinically and genetically. It is associated with a high rate of mortality and poor quality of life for survivors. Management requires a comprehensive approach from multiple specialities to improve their well-being. Although cystic hygroma is a rare feature of this syndrome, its presence further worsens the prognosis of Roberts syndrome and should lead to an earlier proposal for medical termination of pregnancy.

Learning points.

• Roberts syndrome is a rare genetic disorder with multiple organ affections. This case describes an association of cystic hygroma with Roberts syndrome.

• The diagnosis of Roberts syndrome is suspected or presumed based on phenotypic features; however, the gold standard for diagnosis is by cytogenetics. The ESCO2 gene mutation is the recognised gene for the disorder.

• This case highlights the importance of early prenatal diagnosis, genetic counselling and a multidisciplinary approach to managing such a rare syndrome. Despite that, it has a high mortality rate and a poor prognosis for the survivors.