This month we are back with another “Meet the Members” interview. I was lucky to have the opportunity to interview Professor Francesco Muntoni, who I had the privilege of briefly meeting at the WMS 2023 Congress. From previous mentions of his name, it was clear to me that Professor Muntoni has experience in the breadth and depth of neuromuscular conditions, both at the basic genetic level as well as clinical manifestations. Through this interview, I learned the remarkable dedication Professor Muntoni has to his work, which is reflected in the innumerable contributions he has made to the field as a whole.  

Professor Francesco Muntoni is Professor and Chair of Paediatric Neurology at Great Ormond Street Hospital (GOSH), affiliated with University College London (UCL). He is the Director of the Dubowitz Neuromuscular Centre (UCL Institute of Child Health) and also of the Genetic Therapy Accelerator (and UCL Institute of Neurology).

Professor Muntoni shared with me that the early part of his training was in Sardinia, Italy, where he completed a medical degree in Neuropharmacology. He found himself wanting to do more clinical work so he joined a training program in the Child Neurology and Psychiatry Department to gain more clinical exposure. But he never lost his interest in basic science – he explained to me after his daily dose of clinical work was complete at around 4pm, he would continue his work in a molecular genetics lab running PCRs late into the night.

This passion did not go unnoticed by one of his mentors, the late Professor Antonio Cao, who established the Northern Hemisphere Reference Centre for Beta Thalassemia. Professor Muntoni spoke so highly of him, describing him as someone with an “encyclopaedic level of knowledge”, and well-versed in inherited conditions which are frequent in Sardinia. As an aside, I learned that one fourth of individuals on the island are beta-thalassemia trait carriers, one third of males are G6PD deficient and there is a large population of patients who have Wilson’s disease.

Professor Cao observed Professor Muntoni’s interest in understanding the mechanisms and genetics of disease and suggested a field where this interest may prove fruitful – muscle disease. Professor Cao knew Professor Dubowitz in London and wrote a letter introducing Professor Muntoni. After securing funding from the British Council, Professor Muntoni relocated to London for a year for clinical training under Professor Dubowitz. Once again, as in Italy, once his clinical duties were complete, he would spend his evenings back at the bench.

Professor Muntoni completed his training around the time the dystrophin gene was identified when everyone was chasing the genetic and molecular basis of Duchenne muscular dystrophy. This heavily influenced his early academic interests, and when he returned to Sardinia to complete his training, this followed him.

Professor Muntoni has had many achievements in his career, but one which was memorable for him was during this time when he came across a family with multiple indications of dystrophinopathies but a selective cardiomyopathy phenotype. He was able to characterise the unique mutation and plausible explanation for this presentation (DOI: 10.1056/NEJM19930923329130). This convergence of genetics to clinical practice allowed him to build confidence as a translational researcher and served as a launchpad for multiple grants and funding.

In 1993, a position in London opened up and he moved back to the United Kingdom. It is now more than 31 years since he left Italy. At that time, the genetics of Duchenne and spinal muscular atrophy had been discovered, but the search for even rarer inherited muscle diseases continued. In London, he had the privilege of seeing many complex and undiagnosed patients with suspected congenital muscular dystrophies and myopathies at the time. Throughout his career, Professor Muntoni has led and collaborated in many efforts, deep phenotyping and identifying upwards of 25 genes for undiagnosed patients. Naturally, this has more recently led to his work in characterising the genotype-phenotype correlations and variability of these genetic diseases and designing natural history studies as the era of genetic therapies is evolving.

The team of the Dubowitz Neuromuscular Centre enjoying an international food evening together away from the office.

During his 31 years in London, there has been some reorganisation to the structure of the hospital system but currently, Professor Muntoni works at the Great Ormond Street Institute of Child Health, part of the University College London (UCL), where he sees patients two days a week. The rest of his time is focused on his research and clinical trials. He is one of the co-directors of the International Centre for Genomic Medicine in Neuromuscular Diseases, similar to Professor Straub, and is the Director of the Dubowitz Neuromuscular Centre in the Institute of Child Health, and a recently established Genetic Therapy Accelerator Centre in the neighbouring UCL Institute of Neurology.

It was clear to me throughout the interview that Professor Muntoni has reached excellence and well-deserved acknowledgement both through hard work and a strong sense of collegiality and collaboration towards everyone in the field. He feels his career “has been blessed by collaborations” and attributes much success to colleagues around the world who he has had the opportunity to work with in identifying the genetic basis of undiagnosed diseases, as well as expanding their known phenotypes for the neuromuscular community at large.

While he has had lots of these experiences, he shared one specific example of two unrelated Turkish families with MYL1 related congenital myopathy identified years apart, one in London and the second in Perth, Australia by Associate Professor Ravenscroft’s team (doi: 10.1093/hmg/ddy320). He emphasised that it is “not about how good you are but knowing your limitations” and seeking help from colleagues in the field when you have reached the end of your knowledge.

Professor Muntoni presenting at the European Paediatric Neurology Society Meeting in Prague in June 2023.

With the identification of genetic aetiologies in rare and ultrarare disease, he states the nature of the changing world is one in which “the ‘experts’ are the patients” rather than the physicians and investigators. Despite our ever-evolving knowledge of the genetic and molecular basis of disease, he reminded me of the importance of developing fundamental clinical skills necessary to be an astute neuromuscular clinician and researcher – there is a lot to learn from each and every patient.

We discussed how important it is to examine patients in detail and build a strong clinical differential diagnosis prior to interpreting work up, such as muscle biopsies at weekly pathology meetings or genetic variants of uncertain significance. In fact, they start all pathology reading sessions with the clinical features of the patient biopsied and an attempt at a clinical diagnosis prior to pathologic discussion. It is a practice Professor Muntoni maintains and teaches those who come to work with him. He encouraged me that it is always okay for this hypothesis to be wrong, but making this a part of daily practice is how we get better as young trainees and faculty at our clinical evaluation.

He spent some time during our interview teaching me as well! I learned a little trick on physical examination in differentiating muscle versus nerve disease in patients with distally wasted phenotypes. Emery-Dreifuss and collagen VI related muscular dystrophies, for example, can have similar appearing phenotypes to neuropathies. Professor Muntoni learned from a colleague to look at the extensor digitorum brevis muscle. In most paediatric patients with a myopathic processes, this muscle’s bulk is normal or hypertrophied, compared to atrophy in neuropathies or neuronopathies. While this is not fool-proof, I will definitely be incorporating evaluation of this muscle’s bulk going forward.

While I have thus far only been to the last two WMS Congresses, I learned that Professor Muntoni is one of the handful who has been at EVERY SINGLE ONE since its inception! Professor Muntoni remembers the time when it was a “small club” but is excited about the growth of the community. He feels that the Congresses have been helpful to link with others in the field, forge collaborations and establish consortia, for example on congenital muscular dystrophy, that lead to grants and furthering knowledge.

He specifically loves that the Congress honours excellence, but also seeks out the upcoming excellence in the field, highlighting early and mid-career upcomers in the featured talks. He believes in and hopes the Congress continues encouraging an environment of bettering the science rather than one of non-productive criticism. You will find him active and engaged in many of the sessions throughout the week, but he also finds some time for fun! In fact, for the past 20 years, he has a group of colleagues and close friends he goes out to a fancy social dinner with in each city, trying out a new restaurant the group chooses months in advance. I wonder where he will try in Prague this year.

Professor Muntoni at the 2015 WMS Congress in Brighton, UK which he co-organised with Professor Quinlivan. This is a photo of the 10 people, at the time, who had attended all 20 congresses held by the WMS to date.

With all the work he does, it is hard to imagine how Professor Muntoni takes time out for his hobbies. And yet, he is also a gardener like several of our previous featured members. He admits that he loves doing things with his hands, including tending to his garden which he finds therapeutic. Harvesting summer tomatoes, growing roses and flowers, and tending to a tree from Sardinia from which he uses the prunes for a winter liqueur, the garden keeps him busy year-round. He says he has lived in his current home for 20 years and enjoys doing home improvement projects to keep occupied on his days off.

A variety of flowers growing in Professor Muntoni’s beautiful garden.

And did you know Professor Muntoni has built three boats? When he was a young boy in Italy, his father used to have a sailboat. During his childhood summers, he would spend time in a safe bay where he would practice his sailing and hold informal regattas with another boy who was spending his summers there. Professor Muntoni built his first boat when he was 21 years old. To this day, he loves sailing and being on the water, and has a group of friends who will get together and hire a boat on the Croatian coast or British Virgin Islands.

Professor Muntoni out sailing one of his boats! Look at the beautiful places he explores through his unique hobby.

Controversially, despite his Italian heritage, Professor Muntoni is not an avid football fan, which aligns with his expressed interest in “doing things” rather than just watching from the sidelines. I am sure sailing, gardening and handy work, along with going to the cinema with his wife or traveling with his two daughters during long weekends keeps him occupied outside of his busy work schedule.

Interviewing Professor Muntoni was truly an honour and privilege this early in my training. He exemplifies true dedication and the spirit of collaboration in the hopes of advancing the field – qualities of a true leader. And despite his full schedule, he graciously took time out of his day to share his story with me. I hope we reunite again in person in Prague, but also as future collaborators in the coming years!

Author: Ruchee Patel, MD (Paediatric Neuromuscular Fellow PGY-6, The Johns Hopkins University of Medicine, and Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health)