Acta Neuropathol (1992) 83:670 - 674
Acta Niui6pathologica (~) Springer-Verlag 1992
An unusual demyelinating neuropathy in a patient with Waardenburg's syndrome J. M. Jacobs 1 and J. Wilson 2 1 Department of Neuropathology, Institute of Neurology and the National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK 2 Department of Neurology, Hospital for Sick Children, Great Ormond Street, London WC1N 3JH, UK Received October 17, 1991/Accepted December 16, 1991
Summary. W e p r e s e n t clinical a n d l a b o r a t o r y d a t a f r o m a patient with Waardenburg's syndrome type II comprising iris h e t e r o c h r o m i a a n d d e a f n e s s , c o m p l i c a t e d b y H i r s c h s p r u n g ' s d i s e a s e - a k n o w n a s s o c i a t i o n - a n d an unusual demyelinating peripheral neuropathy- a unique a s s o c i a t i o n . T h e n e u r o p a t h y is c h a r a c t e r i s e d b y excessive focal f o l d i n g o f m y e l i n s h e a t h s . I t is o u r v i e w t h a t , although both disorders could represent the conseq u e n c e s o f n e u r a l crest e m b r y o p a t h y , it is m o r e l i k e l y that they are associated by chance. Key words: W a a r d e n b u r g ' s s y n d r o m e t y p e I I - H i r s c h sprung's disease - Demyelination - Hereditary motor and sensory neuropathy - Myelin sheath folding
The recognition of a number of distinctive syndromes associated with long-segment Hirschsprung's disease h a s p r o m p t e d t h e s u g g e s t i o n t h a t all h a v e a c o m m o n o r i g i n in m a l d i f f e r e n t i a t i o n o f n e u r a l crest p r o g e n i t o r s . T h e s y n d r o m e s i n c l u d e c o n d i t i o n s as d i v e r s e as W a a r d e n b u r g ' s s y n d r o m e (iris h e t e r o c h r o m i a , d y s t o p i a canthus, poliosis and cochlear deafness) and the syndrome d e s c r i b e d b y H u r s t et al. [5] o f H i r s c h s p r u n g ' s d i s e a s e , colobomata and cerebral dysgenesis. We report a patient with typical features of Waardenburg's syndrome, colonic aganglionosis, and a severe and apparently progressive neuropathy: an association not previously reported.
Case history The child, a male, was born normally at term weighing 3 kg after a normal pregnancy. He was the first child of healthy nonconsanguineous parents, with two normal brothers. There was no family history of neurological or dysmorphological abnormalities. On the 1st day he developed intestinal obstruction and at laparotomy at the Hospital for Sick Children, long-segment Offprint requests to." J. M. Jacobs (address see above)
Hirschsprung's disease was diagnosed and ileostomy was performed. He spent the next 18 months in hospital with repeated episodes of intestinal obstruction from adhesions, and during this period management was complicated by small-bowel perforation, intraperitoneal abscesses and milk intolerance. Repeated surgery provided opportunities for confirming reduction or absence of ganglion cells in numerous colonic biopsies. Innervation of the ilium was normal. A pull-through operation at 3 years was unsuccessful and an ileostomy was refashioned. At 4 years he had a brief generalised convulsion when he became dehydrated during an episode of small-bowel obstruction. From an early age it was recognised that he was profoundly deaf, and at 5 years Waardenburg's syndrome type II was diagnosed on the basis of iris heterochromia and congenital deafness. References to the association between Waardenburg's and Hirschsprung's syndromes were noted. He did not sit independently until I year and was never able to stand unsupported, but he did learn to run for a few steps in a lurching fashion. On formal developmental assessment at 2.7 years he performed at a 1.5-year level. He was referred to one of us at 7.4 years because of the recent onset of complex partial seizures for which he took sodium valproate, and because his gait had deteriorated in the previous year. On examination his height and weight were just below the 2rid centile for age and head circumference was 48.5 cm (
Acta Niui6pathologica (~) Springer-Verlag 1992
An unusual demyelinating neuropathy in a patient with Waardenburg's syndrome J. M. Jacobs 1 and J. Wilson 2 1 Department of Neuropathology, Institute of Neurology and the National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK 2 Department of Neurology, Hospital for Sick Children, Great Ormond Street, London WC1N 3JH, UK Received October 17, 1991/Accepted December 16, 1991
Summary. W e p r e s e n t clinical a n d l a b o r a t o r y d a t a f r o m a patient with Waardenburg's syndrome type II comprising iris h e t e r o c h r o m i a a n d d e a f n e s s , c o m p l i c a t e d b y H i r s c h s p r u n g ' s d i s e a s e - a k n o w n a s s o c i a t i o n - a n d an unusual demyelinating peripheral neuropathy- a unique a s s o c i a t i o n . T h e n e u r o p a t h y is c h a r a c t e r i s e d b y excessive focal f o l d i n g o f m y e l i n s h e a t h s . I t is o u r v i e w t h a t , although both disorders could represent the conseq u e n c e s o f n e u r a l crest e m b r y o p a t h y , it is m o r e l i k e l y that they are associated by chance. Key words: W a a r d e n b u r g ' s s y n d r o m e t y p e I I - H i r s c h sprung's disease - Demyelination - Hereditary motor and sensory neuropathy - Myelin sheath folding
The recognition of a number of distinctive syndromes associated with long-segment Hirschsprung's disease h a s p r o m p t e d t h e s u g g e s t i o n t h a t all h a v e a c o m m o n o r i g i n in m a l d i f f e r e n t i a t i o n o f n e u r a l crest p r o g e n i t o r s . T h e s y n d r o m e s i n c l u d e c o n d i t i o n s as d i v e r s e as W a a r d e n b u r g ' s s y n d r o m e (iris h e t e r o c h r o m i a , d y s t o p i a canthus, poliosis and cochlear deafness) and the syndrome d e s c r i b e d b y H u r s t et al. [5] o f H i r s c h s p r u n g ' s d i s e a s e , colobomata and cerebral dysgenesis. We report a patient with typical features of Waardenburg's syndrome, colonic aganglionosis, and a severe and apparently progressive neuropathy: an association not previously reported.
Case history The child, a male, was born normally at term weighing 3 kg after a normal pregnancy. He was the first child of healthy nonconsanguineous parents, with two normal brothers. There was no family history of neurological or dysmorphological abnormalities. On the 1st day he developed intestinal obstruction and at laparotomy at the Hospital for Sick Children, long-segment Offprint requests to." J. M. Jacobs (address see above)
Hirschsprung's disease was diagnosed and ileostomy was performed. He spent the next 18 months in hospital with repeated episodes of intestinal obstruction from adhesions, and during this period management was complicated by small-bowel perforation, intraperitoneal abscesses and milk intolerance. Repeated surgery provided opportunities for confirming reduction or absence of ganglion cells in numerous colonic biopsies. Innervation of the ilium was normal. A pull-through operation at 3 years was unsuccessful and an ileostomy was refashioned. At 4 years he had a brief generalised convulsion when he became dehydrated during an episode of small-bowel obstruction. From an early age it was recognised that he was profoundly deaf, and at 5 years Waardenburg's syndrome type II was diagnosed on the basis of iris heterochromia and congenital deafness. References to the association between Waardenburg's and Hirschsprung's syndromes were noted. He did not sit independently until I year and was never able to stand unsupported, but he did learn to run for a few steps in a lurching fashion. On formal developmental assessment at 2.7 years he performed at a 1.5-year level. He was referred to one of us at 7.4 years because of the recent onset of complex partial seizures for which he took sodium valproate, and because his gait had deteriorated in the previous year. On examination his height and weight were just below the 2rid centile for age and head circumference was 48.5 cm (
