Our little Lucia was born in August 2017 to our absolute delight and excitement as first-time parents in Sydney, Australia. It was an anxious wait for us to finally lay eyes on our little bundle of joy.
The routine morphology ultrasound at the 18th week of our pregnancy detected that Lucia had a thickened “nuchal fold” which is a fold of skin on the back of a baby's neck. Increased thickness may indicate a chromosomal abnormality or genetic disorder.
This detection resulted in an amniocentesis procedure in which amniotic fluid was removed from Karla’s uterus for genetic testing. The genetic testing was conducted against a standard prenatal genetic testing array which looked for many known genetic mutations. The test was inconclusive as no mutations of clinical significance were detected. On the one hand, this result was comforting to us as it meant Lucia did not have a serious genetic syndrome. On the other hand, we were still worried because something may still be wrong, albeit unknown at this stage.
Lucia’s birth was traumatic. She was more than a week overdue which resulted in labour being induced. After many hours with the labour not progressing, lactate tests indicated that Lucia was getting distressed and possibly not getting enough oxygen. Karla was rushed to the operating theatre and a few minutes later Lucia was born via an emergency caesarean. We breathed a huge sigh of relief when we noticed that our little girl looked perfect healthy and her Apgar score was completely normal. We did however notice that Lucia didn’t cry and we thought that somewhat strange, but did not make too much of it. The neonatal doctors and nurses didn’t seem overly concerned about her lack of crying either and jokingly said that we were lucky to have such a relaxed and tranquil baby. After a couple of days, we were discharged and we returned home to start life as a new little family.
During the first couple of weeks at home, some signs started to emerge that something wasn’t right with Lucia. She had a really tough time sleeping and would constantly awake with a startle. She also had some difficulty coordinating her swallowing when feeding. Nevertheless, these issues were not enough of a concern to suspect something much more sinister was afoot and we genuinely believed things will settle down. It was on day 18 after Lucia’s birth when everything changed. Lucia had her first seizure.
If you asked us what we knew about epilepsy or seizures before this fateful day, both of us would have told you that we knew almost nothing apart from the imagery of grown adults violently convulsing. Little did we know that epilepsy could affect babies and that seizures came in a number of different varieties and combinations. Terms such as “tonic” and “clonic” or “partial” and “generalised” were not in our vocabulary. It was only once Lucia was rushed to the Sydney Children’s Hospital in Sydney after suffering her third seizure of the day that these terms became salient. We first noticed that Lucia was doing something strange with her arm and shoulder during the day. By the evening, when she did the same strange rotating movement with her shoulder and arm that we were concerned enough to race her to our hospital emergency department. Even after witnessing these strange movements, we had no idea that what we were seeing were partial seizures. It was very difficult to properly explain what we saw to the emergency doctor and he suspected that these were just normal baby movements. After a few hours of observation and nothing strange happening, the doctor was preparing to discharge us. And then it happened again. Luckily we made the decision to grab a phone and video what was happening while also pressing the emergency call button. By the time the nurses arrived the movement was already over, only lasting about 30 seconds. But this time we had something to show the doctor. As soon as he saw the video he said “you are staying tonight, your daughter is having seizures”. And so started the first night of our first admission to hospital which lasted 2 months.
Lucia’s seizures continued through the night and a bedside EEG confirmed epileptic activity originating from a specific region in her brain. In other words, the seizures were “focal” in nature. Following the EEG confirmation, she was immediately started on Phenobarbitone which was very effective in bringing the seizures under control. At the same time a number of diagnostic tests were undertaken to try and determine the source of the seizures. This included blood tests to look for metabolic problems and a lumbar puncture to check her cerebral spinal fluid for any abnormalities and infections. All results came back clear.
A brain MRI looking for structural abnormalities was also conducted which found her brain to look completely normal. For about a week Lucia had no further seizures and by the second week we were again ready to be discharged. This was when Lucia started having a new type of “tonic” seizures which were more generalised in nature. She contracted and stiffened up like a little statue for up to 20 seconds whenever she was drifting off to sleep. The search for an answer intensified and she was started on a second anticonvulsant called Topiramate. These new seizures persisted unabated and then spontaneously stopped approximately 6 weeks later. We were finally discharged and made it back home.
For a few weeks Lucia was completely seizure free and we were incredibly relieved. It was clear however that Lucia was not progressing developmentally as she should for a baby of her age. She was very floppy and not able to lift her head when lying on her stomach. Her feeding issues also persisted. But she was generally happy and engaging and making eye contact. A few further weeks passed and we started to notice odd leg movements. Her legs repeatedly jerked upwards after waking, although she did not seem to be bothered or upset. Our big fear was that this was the start of Infantile Spasms / West Syndrome, which we had come to know about during our previous stay in hospital.
A return visit to the hospital perplexed Lucia’s neurological team as the movements were not typical of seizure activity or the stereotypical spasms associated with West Syndrome. Lucia’s EEG also did not show any epileptic activity which could explain the strange bilateral movements. At this stage the only conclusion which could be drawn was that this was some sort of movement disorder. At this stage we also managed to be accepted in an academic study conducted under the auspices of Professor Ingrid Scheffer called the Epileptic Encephalopathy Flagship whereby Lucia’s DNA will be subjected to whole genomic testing to look for rare mutations which could explain her symptoms.
The strange leg movements continued for a number of months despite the increase of existing medications and introduction of new anticonvulsants. At this stage, Lucia had regressed developmentally and the clinicians came to the conclusion that she is indeed suffering from Infantile Spasms. Lucia’s EEGs also showed a more chaotic pattern. While not full blown “hypsarrhythmia” which is a hallmark of West Syndrome, it was very concerning. Lucia’s neurologist decided to start Lucia on Prednisone, a steroid which has proven effective against Infantile Spasms. Lucia showed some improvement for a couple of weeks and then the “spasms” started once again. We then tried ACTH (adrenocorticotropic hormone), a very powerful steroid which was injected into her thighs every second day. Unfortunately, ACTH also proved ineffective. Lucia was then started on Vigabatrin, a drug which is also used to treat Infantile Spasms when steroid treatment failed. Despite continued escalations in the dose, it also remained ineffective and Lucia ended up suffering toxicity from the drug which required immediate cessation to prevent brain damage or more seriously death. The odyssey of finding an effective drug continued and we cycled through Keppra, Phenytoin, Sodium Valproate and Lucia was also started on the Ketogenic Diet.
A few days before Lucia’s first birthday, we finally received the results of the genetic tests after an anxious wait for many months. We were extremely nervous to hear the results because we were told genetic epilepsy is very severe and nothing can be done if your child has a genetic condition. The diagnosis was very compassionately delivered to us by the genetic counselling team at Sydney Children’s Hospital, but it felt like our world imploded in that moment.
Lucia has been found to have a very rare genetic mutation affecting the WWOX gene. Not much was known about the gene and the associated syndrome, but from what the geneticists read from rare case reports available on the internet, the prognosis was not good…
Lucia’s genetic tests exposed a microdeletion inherited from dad and a nonsense mutation leading to a premature stop codon from mum, both affecting the WWOX gene which is located on Chromosome 16, specifically at the 16q23.1 locus. At this stage we didn’t fully comprehend how autosomal recessive mutations worked and somewhat puzzled that two different types of mutations could result in such a serious problem just because they are on the same gene. We then started to learn more about how proteins are encoded and subsequently produced and also how cells have surveillance mechanisms in place to prevent the translation of faulty pieces of genetic code. The combination of the two mutations Lucia inherited placed her on the severest end of the phenotypic spectrum as no WWOX protein is expected to be produced at all. The first question we had as parents was – how do we fix this? The only advice Lucia’s medical team could proffer was that there is no known cure for this syndrome and that we should love and enjoy our daughter as much as we can every day. It was very hard to accept the reality that nothing could be done apart from treating her symptoms and keeping her as comfortable and pain free as possible.
But at least we had an answer despite the heartbreaking diagnosis. Finally we had an answer to explain so much of what has been happening to our little Lucia. With that came a degree of relief as we stepped off the diagnostic merry-go-round and started focusing much more on giving Lucia the best life as possible without continuous hospital admissions and MRIs and EEGs and other diagnostic tests. We also embarked on a process of learning as much as we possibly could about the gene and its function and made contact with a number of WWOX researchers who have been incredibly generous with their time and information. It is indeed true that not enough is known about the disease and the exact way a WWOX deficiency affects the brain. However, much has been learnt in the past couple of years and there are a number of highly dedicated scientists working on understanding the disease better and just as importantly to find an effective therapy. We are more hopeful than ever that we will see a therapy emerge in the near future that will make a big difference to Lucia’s quality of life.
In the past year Lucia’s seizures have been brought under control, almost miraculously after such a long time, following the introduction of a new drug called Lamotrigine. We have come to learn that many other WWOX children are also free from seizures after finding an anticonvulsant which worked for them. Our discussions with other parents revealed that most have had a very similar experience and it is therefore very important to keep trying different medications as seizure control is possible. But what is clear is that all WWOX children react differently to the antiepileptic drugs. There is no “one size fits all”.
Lucia is profoundly impaired and she doesn’t have the ability to crawl, roll over or speech. Her neck control is also poor and she is unable to sit unassisted. She is also very vulnerable to infections and we have indeed had numerous hospital admissions due to a variety of bugs.
Due to her impairment she is also developing scoliosis. Lucia receives Occupational Therapy and Physiotherapy twice a week which has proven invaluable to keep her as engaged and ensure her body is kept as active as possible.
She is able to tell us with a little frown that she is annoyed
and with her little upturned mouth when she is content and comfortable
Despite all her challenges Lucia is a happy little girl. While she is not able to express herself in the same way a healthy toddler would, we have learnt to read her facial expressions very well.
Her eyes light up when she hears music and bath time is one of her most favourite activities! She also loves going for walks in the park where she stares at all the trees. Lucia has been through so much but her resilience and beautiful spirit is such an inspiration to us and everyone that meets her!
Caring for a severely disabled child has been very challenging but at the same time taught us as parents so much about the importance of acceptance, patience and also hope.
Of course we would do anything to cure our daughter immediately, but not for one moment do we resent how our lives have changed. Life with Lucia has been a blessing and we love her to bits.