A 40-year-old man was referred because he wished to be informed about the genetic nature of his disorder. He was diagnosed with Charcot–Marie–Tooth (CMT) disease. At 14 months of age, he started walking, but awkwardly due to a bilateral drop foot for which braces were prescribed. On first examination at age 2 years and 8 months, there was marked atrophy, hypotonia, and areflexia of the lower legs, and slight wasting of the thenar and hypothenar. At that time, nerve conduction studies showed normal motor conduction velocities of arm nerves. No motor unit action potentials could be recorded in the lower leg muscles on concentric needle examination.

A 54-year-old man was referred by his GP. He had lived with his mother until her death when he was 47 years old. He then moved into an assisted living facility. His father had died in his early 30s in a car accident. A sister was said to have died of a muscle disease and a brother had reportedly died of a heart attack at age 35 years. A niece from his father’s side was also reported to have a muscle disease. Apart from having difficulties opening his hands since childhood (upon request) he had had no complaints until his late thirties, when he experienced muscle weakness. This hampered him during his full-time work as a groundskeeper in public gardens, but he continued working. Two months ago, however, he had to give up this job because of severe fatigue and increasing generalized weakness.

A 55-year-old man had had muscle complaints for as long as he could remember. He could not stretch his arms or walk without shoes due to deformities of the feet. Proximal muscle weakness was mild and slowly progressive over years, and contractures had always been prominent. His stamina was low, but he still worked full-time as a manual worker. He was otherwise healthy.

Family history revealed that his father was similarly affected. In addition, a half-brother and half-sister not only had contractures but also had muscle weakness. The latter underwent surgery for torticollis in the neonatal period.

After a normal pregnancy without hydramnios, delivery of a healthy-looking girl was uneventful. At four months of age, she had had a respiratory infection and was noted to have a weak cough. At eight months of age she was just able to keep her head in an upright position but was not able to sit unsupported. Her mother admitted that she had not been very active since birth, but there was no progressive muscle weakness and no swallowing difficulty. She was referred to a paediatric neurologist because of a suspected neuromuscular disorder. The parents were healthy and there was no consanguinity.

Within a period of a few days, a 34-year-old woman developed progressive weakness of the right leg without pain. Having suffered spontaneous bone fractures as a child, she had been diagnosed with insensitivity to pain syndrome. She had never been able to perspire; this meant warm weather was not well tolerated and it resulted in an increase in body temperature. The tip of the right thumb had been amputated following a skin ulcer (‘panaritium’).

Since early childhood, a 22-year-old-man had difficulty keeping up with his peers at gym class activities. He noticed increasing weakness in his leg muscles when getting up the stairs, and gradually his arm muscles were also involved. He had noticed rolling movements of his thigh muscles triggered by exercise and squeezing the muscles.

Family history was positive: his brother, mother, maternal grandfather, maternal aunt, and nephew had similar complaints.

A 60-year-old woman was referred because from the age of 50 years onwards she experienced muscle weakness that led to increasing difficulty in climbing stairs. In addition, she complained about exercise-induced myalgia.

History included cataract surgery at the age of 58 years, and lately, unexpected and unexplained falls. Family history revealed early-onset cataract in several paternal family members. Her father and brother had died suddenly and unexpectedly despite a pacemaker.

A 24-year-old man is the youngest of five children and of Turkish origin, who since the age of five years had noticed that he was not able to fully extend his arms. Furthermore, his Achilles tendons were taut. His previous history was unremarkable. An older brother had similar symptoms. Both had no cardiac symptoms. His parents were not affected.

A 68-year-old woman was referred because of slowly progressive difficulty climbing stairs. Four years earlier, she had had ptosis surgery of both eyes. Her mother had been diagnosed with progressive external ophthalmoplegia at the age of 69 years. She denied having swallowing difficulties, but her daughter stressed that eating biscuits took her much longer than others.

In his late twenties, a 30-year-old man reported difficulty with raising his arms and running, which had progressed over subsequent years. During his teens he had been a very good soccer player.

In her early forties, a 51-year-old woman first noticed fatigue when walking. She attributed this to hollowing of her back and a tendency to push her tummy forward. Later, she noticed difficulty and pain in lifting her right arm. She had never been able to whistle properly. Her parents and sisters did not have muscle complaints.

Vascular Ehlers-Danlos syndrome (vEDS) is a genetic disease that has an autosomal dominant pattern of inheritance and is caused by mutations in the COL3A1 gene, resulting in type III collagen synthesis defect, making blood vessels and organs particularly fragile and vulnerable. Vascular complications typically include arterial ruptures but also arterial dissections, which can cause ischaemia in the territory involved; visceral complications are also frequently reported. Patients may show a characteristic facial appearance; joint’s hypermobility and translucent skin with easy bruising are commonly found. Diagnostic criteria have been proposed to improve the diagnosis of this rare disorder, although the genetic confirmation is still required. There is no established treatment, so primary and secondary prevention play a key role in the management of these patients. For example, when a cerebrovascular event, such as a stroke, occurs as a result of a spontaneous dissection of a blood vessel, long-lasting antithrombotic therapy, which is the standard secondary prevention in stroke, is actually contraindicated, considering the high risk of bleeding associated with this disease