Abstract Observations have been made on the peripheral nerve changes in four patients, ranging in age from 4 to 32 years, with the congenital cataracts facial dysmorphism neuropathy syndrome. Myelinated fibre density was within normal limits. The salient abnormality was diffuse hypo- myelination which, in the older patients, was associated with demyelination and then axonal degeneration. These findings could be correlated with the relative preservation of sensory action potential amplitude despite markedly re- duced nerve conduction velocity. Unmyelinated axon den- sity was preserved. The morphological observations sug- gest the operation of a developmental process affecting my- elination with a later superimposed degenerative disorder. Key words Peripheral neuropathy · Hypomyelination · Dysmorphism · Cataracts Introduction The congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome is a complex autosomal recessive disorder recently discovered in Wallachian gypsies in Bulgaria [14]. The disorder is recognisable from infancy by the presence of congenital cataracts and microcorneas. Affected individuals are of reduced stature and have a moderate nonprogressive cognitive deficit. Characteristic facial dysmorphism becomes evident during childhood consisting of a prominent midface with a large nose, ante- riorly directed incisor teeth, fleshy perioral tissues and hy- pognathism. These features are more apparent in males. A distally accentuated, predominantly motor peripheral neu- ropathy regularly develops during childhood, initially af- fecting the lower and later the upper limbs. Secondary skeletal changes including foot deformity and kyphoscol- iosis are frequent. Hypogonadotrophic hypogonadism, leading to sec- ondary amenorrhoea in females, is an additional feature. Mild chorea, upper limb postural tremor and mild ataxia and evidence of corticospinal tract dysfunction are seen in some patients. Nerve conduction studies [14] demonstrate a reduction of motor nerve conduction velocity into the demyelinating range. Sural nerve biopsy specimens have been obtained from four individuals with the CCFDN syndrome. The findings of a light and electron microscope and teased fibre analy- sis are documented in this report. Materials and methods Patients Sural nerve fascicular biopsy was undertaken in four male individ- uals with the CCFDN syndrome aged 4, 10, 23 and 32 years with informed consent (from the parents for the two younger patients). The specimens were obtained from a standard site posterior to the lateral malleolus under local anaesthesia. A quadriceps muscle biopsy was also obtained from case 3 (aged 23 years). Tissue processing The specimens were fixed in 2.5% glutaraldehyde in PIPES [piperazine-N-N′-bis (2-ethane sulphonic acid)] buffer [2]. After postosmication in 1% osmium tetroxide in PIPES buffer contain- ing 1.5% potassium ferricyanide and 3% sodium iodate, the speci- mens were dehydrated through increasing concentrations of ethanol and embedded in Durcupan via 1,2-epoxypropane. Semi- thin sections were stained with thionin and acridine orange [11] for I. Tournev · R. H. M. King · J. Workman · M. Nourallah · J. R. Muddle · L. Kalaydjieva · K. Romanski · P. K. Thomas Peripheral nerve abnormalities in the congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome Acta Neuropathol (1999) 98 : 165–170 © Springer-Verlag 1999 Received: 5 October 1998 / Revised, accepted: 18 December 1998 REGULAR PAPER I. Tournev Medical University and Ethnic Minorities Health Problems Foundation, Sofia, Bulgaria R. H. M. King · J. Workman · M. Nourallah · J. R. Muddle · P. K. Thomas () University Department of Clinical Neurosciences, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK Tel.: +44-171-794-0500, Fax: +44-171-431-1577 L. Kalaydjieva Centre for Human Genetics, Edith Cowan University, Joondalup Campus, Perth, Western Australia, Australia K. Romanski National Center for Neurosurgery, Sofia, Bulgaria