Neuroaxonal dystrophy presenting with neonatal dysmorphic features, early onset of peripheral gangrene, and a rapidly lethal course

Abstract

Infantile neuroaxonal dystrophy (IND) is a well-established autosomal recessive neurodegenerative disease. Clinical signs generally begin toward the end of the first or during the second year of life. We are aware of at least 4 cases of pre- or perinatal onset of this condition, and report here on 2 brothers who were affected at birth and had an unusual clinical course with onset of peripheral gangrene that progressed to autoamputation of digits. Both boys died in infancy with pathological changes compatible with IND. The somewhat different clinical course in these brothers leaves open the possibility that this is a variant of neuroaxonal dystrophy due to an X-linked recessive mutation.

Recessive truncatingNALCNmutation in infantile neuroaxonal dystrophy with facial dysmorphism

“…The features not common to INAD included facial dysmorphism and skeletal anomalies. Facial dysmorphism was reported in two other INAD siblings;13 however, the additional atypical findings such as early onset peripheral gangrene and a rapidly lethal course were not found in our patients. The older of our patients is 21-years-old at present, surviving much longer than INAD patients with PLA2G6 mutation.…”

Axonal Dystrophy Presenting as the Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome

“…Cases with multiple congenital anomalies and autoamputation of digits are described. Involvement of the spinal cord and autonomic nervous system is more common than in the infantile form (7).…”

A Case of Infantile Neuroaxonal Dystrophy of Neonatal Onset

“…4 Anecdotal cases of prenatal or neonatal onset are rarely reported but in pre-molecular era and with dysmorphic features and early onset of peripheral gangrene. 5,6 In particular, the authors reported 2 brothers who were affected at birth with onset of peripheral gangrene that progressed to autoamputation of digits 6 ; the presence of pathologic changes compatible with infantile neuroaxonal dystrophy could be related to a severe form of peripheral axonal neuropathy resulting in peripheral gangrene. From the clinical point of view, the onset of disease was unusual.…”