Gut1992;33: 1421-1423 1421

CASE REPORTS Gut: first published as 10.1136/gut.33.10.1421 on 1 October 1992. Downloaded from

Familial coexistence of achalasia and non-achalasic oesophageal dysmotility: evidence for a common pathogenesis

C J O'Brien, H L Smart

Abstract considerable improvement in his ability to In five of seven siblings of healthy parents, swallow and had gained weight. He had no dysphagia developed during adolescence or disturbance of bowel habit or evidence of intest- early adult life. A barium swallow was normal inal obstruction distal to the cardia on plain in one patient but showed appearances con- abdominal x ray. Further enquiry into the sidered to be consistent with achalasia in all patient's family history showed that in addition others. Oesophageal manometry was success- to his younger brother who had previously fully performed in four of the five patients, undergone operation (sibling 2), three other including the patient with symptoms but members of his family (two brothers and one normal radiological appearance. One patient sister: siblings 3, 4, and 5) also suffered from had achalasia, two had oesophageal body long standing dysphagia for solids, although this motor dysfunction associated with a hyperten- had not been investigated. sive, but normally relaxing lower oesophageal sphincter, and one had diffuse oesophageal spasm alone. The occurrence of three differ- SIBLING 2 ent oesophageal dysmotility disorders within Review of this patient's notes showed that five members of a single sibship suggests that these years previously, when aged 16, he had been

conditions are intimately related and probably referred to our own unit with a one year history http://gut.bmj.com/ genetically determined as an autosomal reces- of increasing dysphagia and a recent right basal sive trait. pneumonia. Barium showed achalasia, (Gut 1992; 33: 1421-1423) confirmed by oesophageal manometry (Table). He underwent a Heller's myotomy with fundo- plication and is now asymptomatic. Achalasia is a very uncommon condition with an

incidence in the United Kingdom of less than on September 27, 2021 by guest. Protected copyright. 1/100 000 per annum.' Its cause is unknown and SIBLING 3 although familial clustering can provide clues This 29 year old coal miner had had mild, this is extremely rare and when found usually intermittent painless dysphagia for solids since involves two related cases only.2 12 We have his schooldays but had not sought medical recently seen five siblings with dysphagia from a attention. A barium swallow with marshmallow single family in whom investigation showed a showed no abnormality but oesophageal mano- variety ofoesophageal motor disorders including metry was consistent with the diagnosis of achalasia. This is the largest number of related diffuse oesophageal spasm'3 (Table). He cases of abnormal oesophageal motility ofmixed declined any for his symptoms. types ever documented.

SIBLING 4 Case reports This 22 year old man, also a coal miner, had noted intermittent dysphagia for solids, accom- SIBLING 1 panied by occasional regurgitation of food, for 2 A 27 year old South Yorkshire miner was years. Barium radiology was compatible with referred from his local hospital for pneumatic achalasia (Table). Oesophageal manometry dilatation. He had suffered progressive dys- showed a hypertensive but normally relaxing phagia since the age of 16 years and a barium lower oesophageal sphincter with disruption of Unit, study was reported as showing achalasia (Table). body motor function compatible with an indeter- Royal Hallamshire A younger brother had previously undergone minate oesophageal motility disorder'3 (Table). Hospital, Sheffield investigation and for achalasia. The Because of his symptoms he was treated with C J O'Brien H L Smart subject was unable to tolerate oesophageal mano- sublingual nifedipine before meals which pro- metry. showed food retention within duced Correspondence to: Endoscopy significant improvement. Dr C J O'Brien, Daisy Hill a dilatated oesophagus, associated with a tight, Hospital, Newry, Co Down BT35 8DR. non-obstructed gastro-oesophageal junction. Accepted for publication Pneumatic dilatation was performed. At subse- SIBLING 5 1 1 May 1992 quent clinical review the patient reported a This 33 year old housewife had developed inter- 1422 O'Brnen, Smart

Radiological and manometricfindings in afamily with achalasia and non-achalasic a common pathogenesis, although they seem to oesophageal dysmotility be separate entities. Oesophageal spasm pro- Gut: first published as 10.1136/gut.33.10.1421 on 1 October 1992. Downloaded from Oesophageal manometry gressing to achalasia is infrequently found. Vantrappen and Hellemans observed such an LOSP LOS relaxation swallow with evolution in only 6 of 156 patients they studied. 14 Barium (cmH20)* swallowing Body motility In vigorous achalasia, with which diffuse Sibling 1 Dilated; food residue, distal Unable to tolerate manometry obstruction oesophageal spasm can be confused, orderly Sibling 2 Dilated; food residue, distal 30 Absent Absent relaxation of the lower oesophageal sphincter is obstruction Sibling 3 Normal including marshmallow 25 Normal Repetitive, simultaneous invariably absent.'5 It is improbable that three of study waves (>65%); some the patients we describe could have varient normal peristalsis Sibling 4 Dilated; distal obstruction 52 Normal Repetitive, simultaneous achalasia since all had normally relaxing sphinct- waves; low amplitude; ers. Also against evolving disease is the observa- no normal peristalsis Sibling 5 Normal; delayed marshmallow 45 Normal Repetitive, simultaneous tion that the sibling with classical achalasia had transit waves; low amplitude; the shortest history while those with indeter- no normal peristalsis Sibling 6 Not performed 24 Normal Normal peristalsis minate dysmotility had either very longstanding Sibling 7 Not performed 22 Normal Normal peristalsis dysphagia or had developed oesophageal dilata- Mother Not performed 27 Normal Normal peristalsis tion. LOS=lower oesophageal sphincter; LOSP=lower oesophageal sphincter pressure. Earlier reports describing the coincidence of *Normal range for our laboratory 10-35 cmH20. achalasia and diffuse oesophageal spasm in a mother and son9 and brother and sister'6 pair may be further examples of dysmotility disease link- mittent dysphagia for solids in childhood. There age. Interpretation of these reports is tempered was no chest pain. Standard barium radiology by the fact that oesophageal manometry was not was normal but there was a considerable delay in performed in one of each pair before sphincter the transit of a half marshmallow from the surgery, and in one further case the diagnosis of cricopharyngeous to the stomach, indicative of a achalasia was made only at post mortem; In other motor disorder (Table). Oesophageal mano- situations, where familial achalasia has been metry showed an indeterminate oesophageal reported on radiological findings alone, the co- motor disorder (Table). occurrence of mixed dysmotility disease may She was initially treated with sublingual have been overlooked. nifedipine to good effect but developed intoler- The appearance of significant oesophageal ance and had side effects of flushing and head- dysfunction in five of seven siblings of healthy aches. Subsequently, diltiazem (60 mg thrice parents is we believe most probably the result of daily) produced almost complete resolution of a genetic trait. Familial clustering with vertical her symptoms. transmission has previously been found but http://gut.bmj.com/ horizontal transmission, although still very rare, is four to five times more common.9 Multiple SIBLINGS 6 AND 7 cases have also been a feature of consanguinous A brother aged 35 and sister 31 years had no marriages.02"17 18 However, Mayberry and oesophageal symptoms and oesophageal mano- Atkinson'9 in a systematic review of over 1000 metry was normal in both cases (Table). first degree relatives of patients with achalasia, did not detect any with primary oesophageal on September 27, 2021 by guest. Protected copyright. dysfunction. These findings and those in our PARENTS own family point, therefore, to the possibility Both parents are in their late 50s and do not have that primary disorders of oesophageal function swallowing difficulties. They are not blood rela- may occasionally reflect the expression of an tives and there is no known family history of autosomal recessive gene. In the future, DNA oesophageal disease. The father was unwilling to studies of achalasia/oesophageal dysmotility attend hospital. Oesophageal manometry in the families may provide clues to the abnormalities mother was normal (Table). at molecular level that could underlie;the development ofthese related disorders.

LABORATORY TESTING We thank Mr R Avill who referred sibling 1, Dr M C CoUims for expert radiological help, Dr C D Holdsworth for review of the Routine haematology and biochemistry were manuscript, and Dr D Kumar of the Centre for Human Genetics, normal in the cases with dysphagia. In particu- Sheffield for chromosomal analysis. lar, there were no electrolyte abnormalities or 1 Mayberry JF, Atkinson M. Variations in the prevalence of evidence of malabsorption and random serum achalasia in Great Britain and Ireland: an epidemiological cortisol values were within the normal range. study based on hospital admissions. Q J Med 1987; 62: 67-74. Oesophageal and duodenal biopsy specimens 2 Nagler RW, Schwartz RD, Stahl WM, Spiro HM. Achalasia in were negative for amyloid. Chromosomal analy- fraternal twins. Ann Intem Med 1963; 59: 906-10. 3 London FA, Raab DE, Fuller J, Olsen AM. Achalasia in three sis on affected siblings (1 and 4) showed a normal siblings: a rare occurrence. Mavo Clin Proc 1977; 52: karyotype. 97-100. 4 Bosher LP, Shaw A. Achalasia in siblings: clinical and genetic aspects. AmJyDis Child 1981;*135: 709-10. 5 Stoddard CJ, Johnson AG. Achalasia in siblings. Br J Suarg 1982; 69: 84-5. Discussion 6 Stein DT, Knauer CM. Achalasia in monozygotic twins. Manometric examination of this unique kinship DigDisSci 1982; 27: 636-40. 7 Zimmerman FH, Rosensweig NS. Achalasia in a father and has documented the co-occurrence of classical son. AmJ Gastroenterol 1984; 79: 506-8. achalasia, diffuse oesophageal spasm, and 8 Tryhus MR, Davis M, Griffith JK, Ablin DS, Gogel HK. Familial achalasia in two siblings: significance of possible indeterminate oesophageal motor disorder. This hereditary role.J. PediatrSurg 1989; 24: 292-5. strongly indicates that these conditions can share 9 Frieling T, Berges W, Borchard F, Lubke HJ, Enck P, Familial coexistence ofachalasia and non-achalasic oesophagealdysmotility: evidencefor a common pathogenesis 1423

Wienbeck M. Family occurrence of achalasia and diffuse disorders of oesophageal motility. London: WB Saunders, spasm of the oesophagus. Gut 1988; 29: 1595-602. 1976: 59-72. 10 Dayalan N, Chettur L, Ramakrishnan MS. Achalasia of the 15 Sanderson DR, Ellis FH, Schlegel JF, Olsen AM. Syndrome cardia in sibs. Arch Dis Child 1972; 47: 115-8. of vigorous achalasia: clinical and physiologic observations. 11 Badrawy R, Abou-Bieh A. Congenital achalasia of the Dis Chest 1967; 52: 508-17. Gut: first published as 10.1136/gut.33.10.1421 on 1 October 1992. Downloaded from oesophagus in children. J7 Laryngol Otol 1975; 89: 697-706. 16 Kaye MD, Demeules JE. Achalasia and diffuse oesophageal 12 Westley CR, Herbst JJ, Goldman S, Wiser WC. Infantile spasm in siblings. Gut 1979; 20: 811-4. achalasia inherited as an autosomal recessive disorder. 17 Rozycki DL, Rubin RJ, Rapin I, Spiro AJ. Autosomal J Pediatr 1975; 87: 243-6. recessive deafness associated with short stature, vitiligo, 13 Vantrappen G, Hellemans J. Oesophageal spasm and other muscle wasting and achalasia. Arch Otolaryngol 1971; 93: muscular dysfunction. In: Connell AM, ed. Clinics in 194-7. gastroenterology: motility and its disturbances. London: WB 18 Khalifa MM. Familial achalasia, and mental aunders, 1982: 453-77. retardation. Clin Pediatr 1988; 27: 509-12. 14 Vantrappen G, Hellemans J. Diffuse muscle spasm of the 19 Mayberry JF, Atkinson M. A study of swallowing difficulties oesophagus and the hypertensive lower oesophageal in first degree relatives of patients with achalasia. Thorax sphincter. In: Atkinson M, ed. Clinics in gastroenterology: 1985; 40: 391-3. http://gut.bmj.com/ on September 27, 2021 by guest. Protected copyright.