Table of Contents  
CASE REPORT
Year : 2015  |  Volume : 8  |  Issue : 6  |  Page : 766-768  

Microcephaly with ambiguous genitalia


Department of Pediatrics, Aminu Kano Teaching Hospital, Bayero University, Kano, Nigeria

Date of Web Publication19-Nov-2015

Correspondence Address:
Ibrahim Aliyu
Department of Pediatrics, Aminu Kano Teaching Hospital, Bayero University, Kano
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0975-2870.169920

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  Abstract 

Ambiguous external genitalia could cause parental emotional trauma especially in an African setting where early gender assignment is an integral part of our culture. The most common cause of ambiguous external genital in Nigeria is 21-hydroxylase deficiency and depending on the severity of the enzyme deficiency, it may present with an isolated ambiguous external genital while in severe cases it may manifest with electrolyte deficiency and hypoglycemia; however its association with microcephaly is a rare phenomenon. Therefore, the case an 8-month old child whose parents had lost two other children to similar disorder is reported.

Keywords: 21-hydroxylase deficiency, congenital adrenal hyperplasia, microcephaly


How to cite this article:
Aliyu I. Microcephaly with ambiguous genitalia. Med J DY Patil Univ 2015;8:766-8

How to cite this URL:
Aliyu I. Microcephaly with ambiguous genitalia. Med J DY Patil Univ [serial online] 2015 [cited 2020 Oct 24];8:766-8. Available from: https://www.mjdrdypu.org/text.asp?2015/8/6/766/169920


  Introduction Top


Genital examination and gender assignment is an important part of the newborn examination. In most African societies, newborns are named by the 7 th day of life and this process is sex dependent. In rural northern Nigerian setting, cases of ambiguous external genital still attract a name and presence of phallic-like structure irrespective of its length or morphology often attracts a masculine name despite the ambiguity.

Among common causes of ambiguous external genitalia in Nigeria is congenital adrenal hyperplasia (CAH) (46 XX intersex with virilization of the external genital), [1] 21-hydroxylase deficiency accounting for about 90% of all cases [2] of CAH others include 11 beta-hydroxylase deficiency. [3] CAH may present with systemic complaints depending on the severity of enzyme deficiency (such as vomiting, hypoglycemia, hyperkalemia, hyponatremia) in addition to genital malformation; however its association with microcephaly to the best of the author's knowledge is a rare finding; therefore the case of an 8-month-old child with microcephaly and CAH is reported.


  Case Report Top


An 8-month-old child with ambiguous genitalia presented with protracted vomiting since birth; the child was delivered at term to a 28-year-old mother in a consanguineous marriage setting. She had lost two other children with similar complaint of protracted vomiting with ambiguous genitalia and small head at the age of 7-month; the pregnancy and delivery were not adversely eventful and the child was raised as a male child. The child had delayed motor, speech milestones with small head, which was noticed since birth and the birth weight was 2.5 kg.

The child was small for age with small head and patent anterior fontanel [Figure 1]; occipitofrontal circumference [Figure 2] of 36.8 cm (<−3 standard deviation for a male/female child); weight of 5 kg (z score of −3.85); length of 66 cm (z score of −1.15); the external genital was ambiguous [Figure 3] with stretched phallic length of 1.5 cm, absent dorsal hood, with rugated folds and absent gonads. Abdominopelvic ultrasound revealed presence of uterus and magnetic resonant imaging of the brain was not remarkable; electrolyte and urea revealed hyponatremia, hyperkalemia, acidosis with hypochloremia; while assay for 17-hydroxyprogesterone was markedly elevated (500 ng/dl); cortisol was 1 ug/dl (5-24 ug/dl); testosterone was 20 ng/dl (<3-10 ng/dl); karyotyping was 46 XX; based on these finding a diagnosis of CAH; microcephaly, virilized 46 XX and failure to thrive was made. The child was started on hydrocortisone and fludrocortisone; and advice on stressor doses of the steroid during illnesses were also communicated to the parents. Vomiting subsided with normalized electrolytes. Parents were counseled on the need for proper sex assignment. Fourth week on steroid replacement therapy, the child developed a febrile illness with diarrhea and vomiting while at home but passed away before they could access any health facility.
Figure 1: Small head with ambiguous external genitalia

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Figure 2: Occipitofrontal circumference of 36.8 cm

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Figure 3: Ambiguous external genitalia

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  Discussion Top


Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder; [4] therefore consanguinity increases the risk of transmission of the defective gene. Deficiency of this enzyme predisposes to vomiting, dehydration and metabolic, and electrolyte derangements such as hypoglycemia, hyponatremia, hyperkalemia, metabolic acidosis [5],[6],[7] as was documented in the index case; this is due to deficiencies of cortisol and aldosterone, which are regulators of salt and water metabolism.

Based on the degree of virilization, the index case could had been classified as prader scale 3, [7] which may be confused with a third degree hypospadias; [8] but the absence of testicular tissue on palpation and ultrasound examination ruled this out.

The presence of microcephaly in this case, was unique; though it appeared a possible variant of the anomaly described by Mégarbané et al. [9] but the absence of seizure and bone malformations made this a distinct entity. Therefore, this report depicts a distinct combination, which hitherto had not been reported.

The child responded to oral steroid replacement therapy; the vomiting stopped, and the electrolytes normalized; however the child succumb following a febrile illness probably due to lack of enough stressor dose of steroid; more so steroids are immunosuppressant hence there is the attendant risk of infection, especially in a resource limited setting with poor hygienic environment. Though the index case was typical of CAH, but other differential diagnoses such as lysosomal storage disease and Smith Lemli Opitz syndrome respectively were possible; but absence of clinical evidences of organ storages such as hepatomegaly, splenomegaly; and other features such as intracranial tumors, anomaly of the nostrils (anteverted nostrils), ocular anomalies, [10] and limb defects (syndactyly of second and third toes and postaxial polydactyly) respectively made them unlikely. The relevance of prenatal diagnosis in other pregnancies cannot be overemphasized especially being a consanguineous union.


  Conclusion Top


The association of CAH with microcephaly is a rarity; this depicts a new disorder noticed in two other siblings in a single family and all resulting in their demise at about same age despite the index case been on steroid replacement therapy.

Declaration of patient consent

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

 
  References Top

1.
Andrew M, Barr M, Davies E, Wallace AM, Connell JM, Ahmed SF. Congenital adrenal hyperplasia in a Nigerian child with a novel compound heterozygote mutation in CYP11B1. Clin Endocrinol (Oxf) 2007;66:602-3.  Back to cited text no. 1
    
2.
Osifo OD, Nwashilli NJ. Congenital adrenal hyperplasia: The challenges of management in a developing country. Afr J Urol 2008;14:138-42.  Back to cited text no. 2
    
3.
Migeon CJ, Donohoue PA. Congenital adrenal hyperplasia caused by 21-hydroxylase deficiency. Its molecular basis and its remaining therapeutic problems. Endocrinol Metab Clin North Am 1991;20:277-96.  Back to cited text no. 3
    
4.
White PC, Speiser PW. Steroid 11 beta-hydroxylase deficiency and related disorders. Endocrinol Metab Clin North Am 1994;23:325-39.  Back to cited text no. 4
    
5.
New MI. Genetic disorders of adrenal hormone synthesis. Horm Res 1992;37 Suppl 3:22-33.  Back to cited text no. 5
    
6.
Miller WL. Congenital adrenal hyperplasias. Endocrinol Metab Clin North Am 1991;20:721-49.  Back to cited text no. 6
    
7.
White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev 2000;21:245-91.  Back to cited text no. 7
    
8.
Wayne H. Examination Paediatrics: A Guide to Paediatric Training. 3 rd ed. Sydney: Churchill Livingstone Elsevier; 2000. p. 132-4.  Back to cited text no. 8
    
9.
Mégarbané A, Chouery E, Mignon-Ravix C, El Sabbagh S, Corbani S, Ghoch JA, et al. Ambiguous genitalia, microcephaly, seizures, bone malformations, and early death: A distinct MCA/MR syndrome. Am J Med Genet A 2011;155A:1147-51.  Back to cited text no. 9
    
10.
Goodwin H, Brooks BP, Porter FD. Acute postnatal cataract formation in Smith-Lemli-Opitz syndrome. Am J Med Genet A 2008;146A:208-11.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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Abstract
Introduction
Case Report
Discussion
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