POLD1 Germline Mutations in Patients Initially Diagnosed with Werner Syndrome.

Segmental progeroid syndromes are rare, heterogeneous disorders characterized by signs of premature aging affecting more than one tissue or organ. A prototypic example is the Werner syndrome (WS), caused by biallelic germline mutations in the Werner helicase gene (WRN). While heterozygous lamin A/C (LMNA) mutations are found in a few nonclassical cases of WS, another 10%-15% of patients initially diagnosed with WS do not have mutations in WRN or LMNA. Germline POLD1 mutations were recently reported in five patients with another segmental progeroid disorder: mandibular hypoplasia, deafness, progeroid features syndrome. Here, we describe eight additional patients with heterozygous POLD1 mutations, thereby substantially expanding the characterization of this new example of segmental progeroid disorders. First, we identified POLD1 mutations in patients initially diagnosed with WS. Second, we describe POLD1 mutation carriers without clinically relevant hearing impairment or mandibular underdevelopment, both previously thought to represent obligate diagnostic features. These patients also exhibit a lower incidence of metabolic abnormalities and joint contractures. Third, we document postnatal short stature and premature greying/loss of hair in POLD1 mutation carriers. We conclude that POLD1 germline mutations can result in a variably expressed and probably underdiagnosed segmental progeroid syndrome.

[A case of ectrodactyly: a private pilot with a single finger on each hand]. / Acquisitions des performances dans un cas d'ectrodactylie.

We report the case of a man with bilateral monodactyly whose sole remaining (third) finger on each hand is sensitive and mobile, and whose wrist motor control is normal. Opposed to the palm, the finger provides sufficient clamp function to manipulate medium-sized objects, while bi-manual grip is used for either very thin or voluminous items. Some gestures, such as using a crank, are achieved by simple palm pressure. His foot deformations have no functional consequences. His excellent driving skills suggested that he would be capable of learning to fly an airplane after two years of training with a private instructor, the Inspector of Civil Aviation and Medical Council of the Civil Aeronautic Board gave him the all-clear. Without the need for special equipment, this man is able to write, to drive a car with a manual gearbox, and now to fly passenger-carrying single-engine planes throughout the world.