Monilethrix with holt-oram syndrome: case report of a rare association.

Congenital hypotrichosis may be due to a number of causes and may have multiple systemic associations. A child born of second-degree consanguineous marriage was found to have monilethrix as the cause of congenital hypotrichosis. A detailed systemic evaluation in the child revealed atrial septal defect and a hypoplastic right thumb leading to a diagnosis of coexisting Holt-Oram syndrome.

INTRODUCTION

Monilethrix is an autosomal dominant disorder of hair shaft with regular thinning of hair shaft with fracture of the hair shaft at constricted points, which is commonly caused due to human hair keratin hHb6 gene located on long arm of chromosome 12.[1] Patients have short and fragile hair not requiring haircut since childhood commonly over the occipital and temporal scalp, but may also involve eyebrows, eyelashes, axillary, pubic or body hair.[2]

Holt-Oram syndrome is a syndrome characterized by limb defects associated with cardiovascular anomalies. It is an autosomal dominant disorder caused due to mutations of TBX5 gene located on a long arm of chromosome 12. The cardiovascular defects are usually in the form of septal defects commonly atrial septal defect. Limb defects range from a hypoplastic thumb, metacarpals, carpals, radius to an absent limb.

CASE REPORT

A 2-month-old female child, first born of second degree consanguineous marriage was brought with complaints of absence of hair over the scalp, eyebrows and body since birth. History of normal sweating was present, but dentition had not erupted. No similar illness was seen in any family members. Examination revealed absence of hair from the scalp, eyebrows and body with presence of hair over eyelashes [Figure 1]. Other examination findings included a hypoplastic thumb on the right side with normal nails [Figure 2].

Figure 1

Clinical photograph showing absence of hair over scalp and eyebrows

Figure 2

Clinical photograph showing hypoplastic thumb

Dermoscopic examination revealed presence of numerous empty follicles, small broken hairs, black dots and hair with uniform nodal dilatations with intermittent constrictions at which there was shaft breakage. This was consistent with monilethrix [Figure 3].

Figure 3

Dermoscopy of scalp showing hairs with monilethrix

Microscopic hair shaft examination could not be carried out as hair were too short for plucking.

X-ray right hand showed intercalary dissection of 1st metacarpal with rudimentary thumb. Echocardiography revealed a 6.9 mm atrial septal defect [Figure 4].

Figure 4

Echocardiography showing atrial septal defect

Thus, a diagnosis of Holt-Oram syndrome with monilethrix was arrived at.

DISCUSSION

Congenital hypotrichosis can be due to number of causes. It can be transmitted as an isolated condition, which has an autosomal dominant inheritance. It can also be associated with papular atrichia, keratosis pilaris, vitamin D resistant rickets, ectodermal dysplasia, Moynahan's syndrome, hypotrichosis simplex, Marie-Unna hereditary hypotrichosis, pseudo-thalidomide syndrome, amino acid metabolism and hair shaft disorders.[3] The common hair shaft disorders, which may present as hypotrichosis include monilethrix, pili torti and pili annulati.

Monilethrix (OMIM #158000) is an uncommon hair shaft defect, which can manifest as congenital hypotrichosis. It presents as beaded and brittle hair. The hair is fragile and usually 1–2 cm long. Broken stubs arise from keratotic papular lesions especially over the occipital area. Trichoscopy shows uniform nodosities with intermittent constrictions at which there is shaft breakage. This is called “regularly bent ribbon sign.” Horny follicular papules appear as big yellow dots with immersion fluid. Perifollicular scaling and keratotic plugs may be seen on dry dermoscopy.[4] Patients with monilethrix show improvement in hair growth after puberty. Monilethtix is associated with trichorrhexis nodosa, nail and teeth defects, retarded growth and juvenile cataracts. Oral etretinate has been used as a therapeutic option in patients with monilethrix.[5]

The conditions where a hypoplastic thumb can be associated with atrial septal defect include Holt-Oram syndrome and VACTERL association. Holt-Oram syndrome (OMIM # 142900) is associated with limb defects such as hypoplastic thumb, metacarpals, carpals or radius defects and cardiovascular anomalies especially septal defects. VACTERL association includes vertebral anomalies, anal atresia, cardiovascular anomalies, especially septal defects, trachea-esophageal fistula, renal defects and limb defects like hypoplastic thumb, syndactyly, polydactyly and forearm bony defects like radial aplasia.

The presentation of monilethrix as congenital hypotrichosis is not very common. In this patient, dermoscopy was the clinching tool for diagnosing monilethrix. The association of Holt-Oram syndrome with monilethrix, in spite of the causative genetic mutations being on the same chromosome, has not been reported to the best of our knowledge.