HK J Paediatr new series 2009Congenital Athelia and Cleft Palate A - PDF document

HK J Paediatr (new series) 2009;Congenital Athelia and Cleft Palate: A Case Report ofTwo Generations CP Abstract MBBS, MRCPCHKK G Correspondence to: Received March 4, 2008IntroductionAthelia (absence of the nipple) is a rare condition. In1965, Trier reviewed this condition and collected 43 casesfrom the literature since the first published report in 1839in his historical review. Most of the reported cases were Wong and Ngday 14. Follow-up investigations were arranged.there was no conclusive syndromal diagnosis made.3 months of age showed benign extra-axial collection ininfancy, otherwise no congenital brain abnormality wasage showed closed patent foramen ovale and no otherPatient received repair surgery for cleft palate, releaseof tongue tie and excision of right pre-auricular sinus inAugust 2007 uneventfully. There is no delay or abnormalgrowth on teeth development. Sweat production has beennormal. Clinical follow-up showed normal growth alongcentiles (Weight = 50th; Height = 75th; Head circumference= 75th). Development milestones have been appropriatefor her chronological age. Physical examination at 2 yearsand 9 months of age revealed bilateral absence of nipple-complexes leaving with a faint mark on nipple area(Figure 1). She also has left-sided low-set ear (Figure 2)and sparse hair (Figure 3). Examination on cardiovascular,respiratory, abdominal, neurological, musculoskeletalPatient's father, HKF, was born in 1954 by normalspontaneous delivery. He was noticed to have bilateralathelia and cleft palate since birth. He received repairsurgery for cleft palate at 5 years of age. He noticed multipleFigure 1Bilateral absence of nipples, taken at 2 years andFigure 2Left low-set ear, taken at 2 years and 9 months of age.Figure 3Sparse hair, taken at 2 years and 9 months of age. since the age of six. He did not

consult any dermatologistsbefore. The macules and nodules increase in numbergradually throughout the years. He was diagnosed to havetuberculosis at the age of 18 and was treated completely.He had gastric ulcer with gastrointestinal bleeding at theage of 20 required partial gastrectomy. His sweat productionhas been normal. His teeth were not peg-shaped beforethough he is now having teeth prosthesis due to multipledental caries. Physical examinations on cardiovascular,respiratory, abdominal, neurological and musculoskeletalsystems are normal. There are bilateral athelia (Figure 4), Congenital Athelia and Cleft Palate nodules (Figure 5) on chest wall and limbs. Skin biopsieson the lesions confirmed the diagnosis of Cherryhaemangioma and Steatocytoma multiplex (multiplesebaceous cysts) respectively.From the above illustration of 2 cases with congenitalathelia and cleft palate involving the consecutivegeneration, underlying inheritable cause should besuspected. We would try to suggest an underlying causeof this rare condition in this family by reviewing theEmbryologyThe mammary glands begin to develop during the sixth They first develop as bilateralventral ectodermal solid growths into the underlyingmesenchyme. These ingrowths grow along the mammaryridges or mammary lines bilaterally (Figure 6) extendingfrom the axillary to the inguinal regions. As time passes,region persist due to an unequal proliferation of cells alongthe mammary line where the breasts are located. Theseresult in the primary mammary bud. The primary mammarybud proliferates and gives rise to the secondary mammarybud which further develops into lactiferous ducts. Thesurrounding mesenchyme will develop into the fatty stromaand fibroelastic tissues of the mammary gland. Theseoverlying the site of origin of the mammary glanddepressed, forming the

shallow mammary pit. Soon afterproliferation of the surrounding connective tissue of theTerminologyThere are in fact multiple terms describing different Athelia is defined as thedevelopmental absence of the nipples. Amastia describes Figure 4Patient's father, bilateral athelia.Figure 5Multiple Cherry haemangioma and Steatocytomamultiplex. Figure 6 Wong and Ngthe developmental absence of mammae (Synonymous Amazia describes the developmentalabsence of the mammary gland. Trier suggested theabove terms are confusing and should use "absence of"Absence of the breast" is defined by the absence of thein "hypoplasia of the breast" but with decreased growthClassification and Literature ReviewTrier reported the largest series of this rare condition sofar. He classified the condition into 3 groups among theTrier documented 7 male cases belonging to the firstgroup in his review. The trait is sex-linked recessive. Theassociated defects mainly involve the skin, teeth, and nails.corresponding pectoral muscles. These cases could berelated to underlying Poland's syndrome which is identifiedby absence of the breast or hypoplastic breast unilaterallyassociated with absent pectoral muscles and othermusculoskeletal defects ipsilaterally. He described 16 casesgroup. Ten of them had no other anomalies associated. Onlyone of them was found to have bilateral absence of the breastand cleft palate. The others had various associatedhair, absence of a finger and lobster-claw deformity of hands Familial inheritance was found in three of thepedigrees in Trier's review. Two of them involved a two-generation transmission and the other involved a three-generation family.Pattern of InheritanceThe family of our index patient consists of four persons.Patient's mother (born in 1972) and elder sister (born in1997) are unaffected and enjoyed good

past health. BothFurther history of both sides of the family revealed no otheraffected individuals.Published case reports in the literature reported differentmodes of inheritance including autosomal recessive,autosomal dominant, X-linked recessive or X-linked In our case, pedigree study suggests anautosomal dominant pattern of inheritance (Figure 7). Theunaffected elder sister excludes a sex-linked dominantinheritance. Since there is no affected individual on paternalparents and all other 6 siblings, it may suggest a de novomutation on patient's father as the underlying cause of thisWe would classify our two patients under the third groupof Trier's classification. The association with cleft palateis rare and our cases add up to the 2nd and 3rd cases of thepublished reports so far. If we review the embryologicaldevelopment of the mammary glands and palate, the timingof the formation of mammary ridge and mammary bud suggested that 1) Hypoplasia of theBreakdown of fusion could be one of the mechanismsresponsible for fusion failure of the processes and givingrise to cleft palate. It is difficult to distinguish whether thetotal under-development of the mammary ridge or theinability of differential cell proliferation involved in theformation of mammary bud in the pectoral area. Themolecular biology of normal and abnormal growth ofFigure 7Pedigree, arrow=index patient, shaded=with athelia Congenital Athelia and Cleft PalateWe are not sure if the multiple Cherry haemangiomataand Steatocytoma multiplex found on patient's father areassociated features of this condition because they were notreported as such in the literature before and yet, they werenot found on our index patient yet.Despite our extensive search in the English literature,this rare condition so far. This could represent the rarity ofthis condition inhe

rently or under-reporting of this conditionManagement issues are expected to arise especiallypregnancy. We anticipate that her breasts will not developduring puberty which could be a very embarrassing orof the breasts and nipples would be an option, but thetiming and strategy of this operation will need furtherplan and discussion with plastic surgeons. Clinicalpsychologist's opinion will also be helpful with regardsto the issues arising from the pubertal development inSummaryAthelia is a rare condition and is almost alwaysreview shows a heterogeneous pattern of presentation inpatient and her father with congenital athelia associatedwith cleft palate and sparse hair but without otherautosomal dominant fashion of inheritance most likelyarising from a de novo mutation on patient's father. Todate, no definite gene locus is identified to explain thisgenetics is required to locate the locus of the involvinggene giving rise to it. Concerning the management ofboth physical and psychological issues should beexpected to arise especially in a female patient. A multi-disciplinary approach involving Paediatricians, PlasticSurgeons and Clinical Psychologists would be the bestReferences1.Trier WC. Complete breast absence. Case report and review ofthe literature. Plast Reconstr Surg 1965;36431-9.2.Lin KY, Nguyen DB, Williams RM. Complete breast absencerevisited. Plast Reconstr Surg 2000;106:98-101.3.Moore KL, Persaud TVN. The developing human, clinicallyoriented embryology, fifth edition. Philadelphia: Saunders, 1998,4.Ishida LH, Alves HR, Munhoz AM, et al. Athelia: case reportand review of the literature. Br J Plast Surg 2005;58:833-7.5.Spraycar M. Stedman's Medical Dictionary, 26th edition.Baltimore: Williams & Wilkins, 1995, p.1058.6.Sommerlad BC. The management of cleft lip and palate. CurrentPaediatrics, 2002:12, p.43