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 Table of Contents  
Year : 2021  |  Volume : 28  |  Issue : 4  |  Page : 298-302

Ablepharon macrostomia syndrome: Absent prepuce in the first case report in West Africa

1 Department of Pediatrics, Faculty of Medicine, Nnamdi Azikiwe University, Awka; Department of Pediatrics, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria
2 Department of Pediatrics, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria

Date of Submission24-Sep-2020
Date of Decision05-Dec-2020
Date of Acceptance13-Jan-2021
Date of Web Publication29-Nov-2021

Correspondence Address:
Dr. Ezinne Ifeyinwa Nwaneli
Department of Pediatrics, Nnamdi Azikiwe University Teaching Hospital, PMB 1025, Nnewi, Anambra State
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/npmj.npmj_318_20

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Ablepharon macrostomia syndrome (AMS) is an extremely rare congenital ectodermal dysplastic disease characterised by craniofacial, skin, skeletal and genital abnormalities. Very few cases have been reported since the first case report in 1977. We report the case of a 6-day-old male delivered to unrelated parents. He was dysmorphic with absent eyelids, eyelashes and eyebrows, large fish-shaped mouth, hyperpigmented thick anterior abdominal wall, absent prepuce amongst other features. Skull X-ray showed poorly developed zygomatic bones. The patient is being managed as a case of AMS in a multidisciplinary fashion. There is no agreement on the mode of inheritance, but authors have suggested autosomal recessive, autosomal dominant, sporadic and familial occurrences. The absence of the prepuce and hyperpigmentation of the anterior abdominal wall as was seen in our patient has not been reported. More case reports are needed to delineate the spectrum of clinical features in AMS.

Keywords: Absent eyelid, congenital anomaly, disfiguring, Nigeria, syndrome

How to cite this article:
Nwaneli EI, Chukwuka JO, Uju CM, Epundu CO. Ablepharon macrostomia syndrome: Absent prepuce in the first case report in West Africa. Niger Postgrad Med J 2021;28:298-302

How to cite this URL:
Nwaneli EI, Chukwuka JO, Uju CM, Epundu CO. Ablepharon macrostomia syndrome: Absent prepuce in the first case report in West Africa. Niger Postgrad Med J [serial online] 2021 [cited 2022 May 20];28:298-302. Available from: https://www.npmj.org/text.asp?2021/28/4/298/331526

  Introduction Top

Ablepharon macrostomia syndrome (AMS) is an extremely rare congenital ectodermal dysplastic disease characterised by craniofacial, skin, skeletal and genital abnormalities.[1] It is an extremely disfiguring syndrome and largely identified by the clinical features. Only a few cases have been reported since the first case report in 1977 by McCarthy and West,[2] but none has been reported in Nigeria. These reported cases have further exposed the clinical features that could be seen in AMS, however, calls for more case reports have been made as the spectrum of clinical features seen in AMS has not been completely identified.[1],[2],[3],[4] Following a careful literature search, the authors have not found any report of AMS in West Africa. This is the aim of this report in addition to further identifying other features that could be found in AMS. This case presented to one of the two tertiary hospitals servicing a State in the South Eastern region of Nigeria. Despite Nigeria's strategic position in Africa, the country is largely underserved in the health-care sphere and the health-care system (personnel and medical equipment) is inadequate and poorly developed.

  Case Report Top

This is a case report of a 6-day-old male neonate born in June 2017 who was referred to the Nnamdi Azikiwe University and Teaching Hospital, Nnewi, Anambra State, Nigeria. The baby was delivered to a 28-year-old primigravida and a 38-year-old man who are unrelated. The pregnancy was carried to 40 weeks gestational age and other than being diagnosed with hepatitis B virus at 28 weeks of gestation; the mother had no problems while pregnant. There was no known history of exposure to teratogens and no family history of congenital abnormalities. Labour was spontaneous and delivery was vertex and vaginal. At birth, the baby required little resuscitation. The attending nurse observed a remarkable abnormality in the baby's features and hence referred them to a tertiary hospital for expert care. However, the parents did not present immediately because they had financial constraints and were not certain the baby would survive. They returned home, but when the baby developed fever, they decided to present to our centre. The baby was said to have been on breast milk only since birth, latches and sucks well. He had not received any vaccination.

On presentation, we found a dysmorphic term neonate who was febrile with an axillary temperature of 38.7°C, alert and has optimal primitive reflexes. The dysmorphic features observed are as illustrated in [Table 1] and [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]. In addition to these features, the patient also had a foul-smelling umbilical stump. Laboratory investigation revealed leucocytosis with relative neutrophilia. Other haematologic and biochemical parameters showed no abnormality. Skull X-ray showed a poorly developed zygomatic bone [Figure 6]. A cranial magnetic resonance imaging could not be done as a result of its unavailability in the hospital in addition to financial constraints; however, a transfontanelle ultrasound scan did not reveal any abnormality. Evaluation of the buccal smear for Barr bodies revealed the absence of Barr body which indicates that the baby was a male, however, there was no scrotal sac and no testes were visualised with an abdominal ultrasound. There were no facilities for genetic testing in the area to determine the mode of inheritance. The parents and grandparents had normal facial features.
Table 1: Clinical features found in the patient

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Figure 1: Marked craniofacial deformities (absent eyelids, eyelashes, eyebrows, ectropion of both eyes, hyperaemia of the bulbar conjunctiva, corneal opacity, cryptophthalmos, milk-coloured eye discharge, fish-shaped mouth, triangular-shaped head and nose and alopecia) at 6 days, 8 months and 2 years old

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Figure 2: Low set malformed ears and flat occiput at 6 days, 8 months and 2 years old

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Figure 3: Ambiguous genitalia, posteriorly places micropenis, absent prepuce, absent scrotum, redundant skin folds at 6 days and 2 years old

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Figure 4: Large umbilical stump (at 6 days of age), large ventral hernia and hyperpigmentation of the anterior abdominal wall at 8 months and 2 years

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Figure 5: Camptodactyly at 6 days and 2 years old

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Figure 6: Skull X-ray showing poorly developed zygomatic bone

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The patient was diagnosed as a case of AMS with early-onset neonatal sepsis and was managed in a multidisciplinary fashion involving the paediatricians, plastic surgeons, ophthalmologists, ENT surgeons, paediatric surgeons, dermatologists, orthopaedic surgeons and social/welfare workers. The paediatricians placed the baby on a 14 days course of antibiotics. The ophthalmologists commenced ocular antibiotics and artificial tears, while the dermatologists introduced the use of emollients on the skin. Hearing screening done by ENT surgeon did not show any hearing loss. The plastic surgeons and paediatric surgeons suggested a cosmetic and sex assigning surgery respectively, but this could not be done due to financial constraints, although the social/welfare workers made efforts to raise funds for the baby. On the 10th day of admission, the parents asked to be discharged as they could not keep up with the admission fees. The patient was discharged home on oral antibiotics to complete the 14 days antibiotic course following a good response to the intravenous antibiotics. He was also given his due vaccinations. They were then asked to present to the outpatient clinic in a week for reassessment.

The patient, however, did not keep up to the hospital appointment. Following several phone calls to the father who cited financial constraint as a reason for their inability to come to the hospital, they visited for follow-up at the 8th month of life. At the follow-up visit, a spontaneously reducible midline ventral hernia measuring 10 cm in its vertical axis and 5 cm in its widest horizontal axis was seen [Figure 4]. The baby had attained gross and social developmental milestones for his age. He had also missed vaccinations scheduled for the 10th and 14th week. All attempts to convince them to visit other specialists involved in his care for further intervention was futile due to lack of funds. They defaulted again from follow-up and represented at the age of 2 years following phone calls. At this age, the patient was unable to walk unsupported, responded to calls, played with other children, but had some language delay as he barely uses monosyllabic words at 2 years of age. The parents again declined referral to a speech therapist.

The parents have undergone series of counselling during their visits and through phone calls. During the counselling, the need for follow-up to monitor the patient's growth and development and offer low-cost medical assistance when necessary and complete his childhood vaccinations were discussed. The parents were also made to understand the rarity of the syndrome and the need to understand its spectrum presentation for academic purposes. The role of facial reconstructive and contracture release surgeries to improve the child's physical appearance was also elucidated. The parents expressed readiness to do whatever was necessary to improve the child's condition and to contribute to medical knowledge on the condition; however, their poor financial situation remained a huge constraint. He also promised to keep up with his childhood vaccinations. He is still being followed up.

  Discussion Top

AMS is an extremely rare congenital anomaly. There is a dearth of literature on this condition in West Africa following careful literature search on Google Scholar and PubMed search engines. Less than 20 cases have been documented since the first report by McCarthy and West in 1977 with a worldwide prevalence of <1/1,000,000.[1],[2] Almost all documented cases were in individuals with non-African origin with only a case documented in an African-American male.[4] Its spectrum of presentation is not yet fully delineated.[1],[2],[3]

There is no agreement on the mode of inheritance, but authors have suggested autosomal dominant, autosomal recessive and familial occurrences.[5],[6],[7],[8] In a bid to identify the cause, in 2015, Marchegiani et al.[5] performed an extensive clinical phenotyping, whole-exome and candidate gene sequencing evaluation on seven persons previously reported to have features of AMS. It was found that all the seven individuals had a recurrent dominant mutation in the DNA binding domain of TWIST2 protein by substitution of lysine at TWIST2 residue 75 (p.Glu75 Lys).[5] TWIST2 encodes a basic helix-loop-helix transcription factor that regulates the development of mesenchymal tissues, hence mutation causes failure of ectodermal-mesenchymal induction as well as defects in the development of prosencephalic neural crest.[3] Although the mutated TWIST2 genes were commonly found on chromosome 18q, de novo mutation of the TWIST2 gene located on chromosome 2 and inversion mutation at chromosome 9 have been reported.[5],[9]

The first reported cases were in two unrelated male children who had similar abnormalities such as absent eyelids, eyebrows, eyelashes, alopecia, fusion defects of the mouth, expressionless facies, rudimentary external ears (but normal hearing), ambiguous genitalia, absent or rudimentary nipples, coarse dry skin with redundant skin folds and delayed expressive language development.[1],[2] All these features were also observed in the index patient, who in addition had a delay in the achievement of some gross and language developmental milestones at his 2-year follow-up. Subsequently, Hornblass and Reifler[10] in addition to the already mentioned features reported failure of lip fusion resulting in a fish-shaped mouth, abnormally shaped ears and nose, absence of lanugo, ventral hernia, ambiguous genitalia and corneal opacity, all of which were identified in our patient. Price et al.[11] identified hypertelorism, protrusion of the maxilla, malformed low set ears and hairless wrinkled skin as additional features. Ferraz et al.[7] also reported low nasal bridge with hypoplastic anteverted nostrils, absent nipples in addition to other features. The index patient being reported has ocular as well as nipple hypertelorism with hypoplastic nipples and malformed nose. Gorlin[12] described the ambiguous genitalia as a posteriorly displaced micropenis, with an absent scrotum and also identified alterations in the abdominal wall which were seen in this patient. However, this patient had no prepuce. Other features identified were absent or hypoplastic zygomatic bone, syndactyly, camptodactyly and short metacarpal bones.[12],[13],[14] Most of these features were also observed in our patient. Hearing loss, poor hair growth, visual problems (nystagmus and retinal detachment), skin scarring and contractures have been identified as chronic problems in these patients.[4],[10],[14],[15] Hyperpigmentation of the skin has not been reported as a feature of AMS. According to Price et al.,[11] skin biopsy was normal in these patients contrary to the finding by Marchegiani et al.[5] who found disrupted elastic fibres with areas of amorphous deposits along abnormally oriented collagen fibres and adjacent areas of microfibrillar proliferation.

The mainstay of treatment is corrective surgery which requires good planning.[1],[4],[12] The patient in this case was admitted without planning for the immediate management of the septic condition. Management of these patients requires a lot of dedication from the family and huge financial investments. A multidisciplinary management plan involving the paediatrician, plastic surgeon, ENT surgeon, dermatologist, paediatric dentist, oro-maxillofacial surgeon, ophthalmologist, psychologist as well as social workers is necessary for a comprehensive care. Eye care with artificial tears and ocular antibiotics are important. Eyelid reconstruction surgeries and corneal surgeries have been performed in these patients but with some improvement.[10],[11],[12] Reconstruction of the mouth, chin, zygomatic arch, ears and breast has also been done in one of the patients.[13] All these only minimally improve the physical looks of these patients.

Barber Say syndrome (BSS) also caused by a mutation in TWIST2 protein with similar features should be considered as a differential diagnosis of AMS. BSS, however, has glutamine or alanine as the substituting amino acid at TWIST2 residue 75 and it generally presents with hypertrichosis. Setleis syndrome which is also caused by TWIST2 mutation also has few of the features seen in AMS, and it has been suggested that AMS, BSS and Setleis syndrome may be a continuum of a genetic disease.[15]

  Conclusion Top

AMS remains an extremely rare congenital anomaly. The absence of the prepuce and hyperpigmentation of the anterior abdominal wall was seen in this patient and these have not been reported. More case reports are needed to be able to delineate the full spectrum of clinical features that can be seen in patients with AMS. A better understanding of this condition will help in the management of these patients.


Due to its scarcity, genetic testing could not be done despite efforts made by the authors.

Informed consent

Written consent signed by the father of the baby presented in the case report giving permission to publish the case and the pictures as depicted was obtained.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the parent has given his consent for images and other clinical information to be reported in the journal. The parent understands that names and initials will not be published and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

National Organization of Rare Disorders. Ablepharon Macrostomia Syndrome. Available from: https://rarediseases.org/rare-diseases/ablepharon-macrostomia-syndrome. [Last accessed on 2020 Dec 24].  Back to cited text no. 1
McCarthy GT, West CM. Ablepharon sic macrostomia syndrome. Dev Med Child Neurol 1977;19:659-72.  Back to cited text no. 2
Kallish S, McDonald-McGinn DM, van Haelst MM, Bartlett SP, Katowitz JA, Zackai EH. Ablepharon-Macrostomia syndrome—Extension of the phenotype. Am J Med Genet A 2011;155A: 3060-2.  Back to cited text no. 3
Larumbe J, Villalta P, Velez I. Clinical variant of ablepharon macrostomia syndrome. Case Rep Dermatol Med 2011;2011:593045.  Back to cited text no. 4
Marchegiani S, Davis T, Tessadori F, van Haaften G, Brancati F, Hoischen A, et al. Recurrent mutations in the basic domain of twist2 cause ablepharon macrostomia and barber-say syndromes. Am J Hum Genet 2015;97:99-110.  Back to cited text no. 5
Sargent LA, Stevens CA. Ablepharon-macrostomia syndrome. Am J Med Genet A 2002;107:30-7.  Back to cited text no. 6
Ferraz VE, Melo DG, Hansing SE, Cruz AA, Pina-Neto JM. Ablepharon-Macrostomia syndrome: First case report of a familial occurrence. Am J Med Genet A 2000;94:281-3.  Back to cited text no. 7
Rohena L, Kuehn D, Marchegiani S, Higginson JD. Evidence for autosomal dominant inheritance of ablepharon-macrostomia syndrome. Am J Med Genet A 2011;155A: 850-4.  Back to cited text no. 8
Feinstein E, Traish AS, Aakalu V, Kassem IS. A case report of ablepharon-macrostomia syndrome with amniotic membrane grafting. Case Rep Ophthalmol 2015;6:366-72.  Back to cited text no. 9
Hornblass A, Reifler DM. Ablepharon macrostomia syndrome. Am J Ophthalmol 1985;99:552-6.  Back to cited text no. 10
Price NJ, Pugh RE, Farndon PA, Willshaw HE. Ablepharon macrostomia syndrome. Brit J Ophthalmol 1991;5:317-9.  Back to cited text no. 11
Gorlin RJ. Orofacial Clefting Syndrome. In: Gorlin RJ, Cohen MM, Hennekam RC, editors. Syndromes of the Head and Neck. 4th ed. Oxford, UK: Oxford University Press;1990. p. 913.  Back to cited text no. 12
Brancati F, Mingarelli R, Sarkozy A, Dallapiccola B. Ablepharon-macrostomia syndrome in a 46-year-old woman. Am J Med Genet A 2004;127A: 96-8.  Back to cited text no. 13
Markouizos D, Siddiqi U, Siddiqi S, Raziuddin k, Nangia B. Ablepharon macrostomia syndrome: Report of a case and clinical delineation. Am J Hum Genet A 1990;47:A66.  Back to cited text no. 14
De Maria B, Mazzanti L, Roche N, Hennekam RC. Barber-Say syndrome and Ablepharon-macrostomia syndrome: An overview. Am J Med Genet A 2016;170:1989-2001.  Back to cited text no. 15


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

  [Table 1]


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