Goltz syndrome: a newborn with ectrodactyly and skin lesions.

Goltz syndrome or Focal Dermal Hypoplasia is a rare multisystem disorder, involving all the three germ cell layers. The disease is thought to be inherited in X-linked dominant fashion with heterogeneous mutations of the PORCN gene at Xp11.23 locus. Majority of the cases are sporadic, mainly due to postzygotic somatic mutations. The clinical spectrum includes characteristic cutaneous manifestations, multiple skeletal anomalies, and involvement of the eyes, hair, nails, kidneys, and so on. Considerable variability is noted in the clinical expression of the disease probably due to genomic mosaicism. Around 300 cases of Goltz syndrome have been reported in the literature. Here, we report such a case with characteristic skin lesions, multiple bony defects, distinctive facial features, coloboma of iris, and bilateral hydronephrosis. The diagnosis was evident immediately after birth due to the characteristic clinical picture of the baby.

What was known?

Goltz syndrome or Focal Dermal Hypoplasia is a multisystem disorder involving skin, musculoskeletal system, eyes, hair, nails, kidney, and so on, with considerable variation in the clinical features.

Introduction

Focal Dermal Hypoplasia (FDH) is a comparatively rare multisystem disorder, characterized by meso-ectodermal dysplasia of genetic origin. It is more commonly referred to as Goltz Syndrome, as Goltz et al. in 1962 first described the condition based on three female patients with similar clinical features.[1] It is believed to be inherited as an X-linked dominant disorder with in utero lethality for homozygous males.[2] Though cutaneous manifestations predominate (evident from the name FDH), characteristic abnormalities are frequently encountered in the eyes, bones, hair, nails, and practically every system of the body.[3] Here, we report a newborn female with ectrodactyly and characteristic skin lesions of Goltz syndrome.

Case Report

A one-day-old female baby born out of a nonconsanguineous marriage with a birth weight of 2 kg was admitted in our nursery with multiple congenital anomalies. The mother was a primigravida with a history of regular antenatal check-ups. The pregnancy was uneventful and ended in an uncomplicated normal vaginal delivery. There was no history of any unusual drug intake by the mother. The family history was also of no significance. On physical examination, there were patchy areas of absent skin cover over the periumbilical region, right-sided inguinal region, and back of the right thigh. A few atrophic areas of skin with alternate hypo and hyperpigmented lines in reticular pattern were noted over the right lateral chest wall and both the pinnas [Figure 1]. The face was triangular in shape with a broad nasal bridge, pointed chin, and thin, broad ears.

Figure 1

Atrophic skin lesions, aplasia cutis congenita, ectrodactyly with true shortening of right lower limb, and syndactyly of right first and second fingers

The right lower limb was grossly shorter than the left one with a characteristic lobster claw deformity, otherwise known as ectrodactyly. Also, there was presence of syndactyly of the first and second fingers of the right hand [Figure 1]. No other skeletal deformity was found. The hair was thin and sparse, but the nails were normal. Ophthalmological examination revealed bilateral coloboma of the iris at the mid-periphery (right > left).

Routine blood counts were normal. X-ray of the right hand showed fused first and second metacarpals, whereas skiagram of the right lower limb revealed the absence of the fibula and all other bones distal to it, i.e. tarsals, metatarsals, and phalanges [Figure 2]. Cranial ultrasound and echocardiography were within normal limits, but abdominal ultrasonography showed bilateral hydronephrosis and hydroureter. Kidney function tests were only mildly deranged. Hence, she was discharged from the hospital with a plan for close follow-up with a multidisciplinary approach. Follow-up at 1 month of age revealed that the atrophic skin lesions had further extended to involve larger areas of the trunk with a more characteristic appearance [Figure 3]. She was otherwise healthy with adequate weight gain. Follow-up ultrasonography (USG) at 3 months showed regression of hydronephrotic changes.

Figure 2

Skiagram of the lower limbs showing absence of right fibula and all other bones distal to it, i.e. tarsals, metatarsals, and phalanges

Figure 3

Follow-up at 1 month of age revealing that atrophic skin lesions have further extended to involve larger areas of trunk with a more characteristic appearance

Discussion

FDH can involve all the three layers, i.e. ectoderm (skin, eyes), mesoderm (bones, teeth), and endoderm (various mucosae) with variable expression.[3] Variation in clinical severity is said to be partly due to lyonization of the X chromosome and partly because of postzygotic genomic mosaicism, which is also responsible for the sporadic cases (95%).[3] Heterozygous and mosaic mutations in the PORCN gene of the X chromosome at the Xp11.23 locus are now well-proven etiology for the pathogenesis of FDH.[456] Although the biochemical functions of the PORCN gene have not been completely characterized, it is known to target Wnt signaling proteins that are the key regulators of embryonic development of the skin, bone, and other structures.[4] Though it is an X-linked dominant disorder mainly affecting females, reports of alive males[7] represent cases of sporadic new mutations or somatic mosaicism,[8] and such cases have always been reported to be the first affected cases in the family.[9]

The predominant feature of FDH is connective tissue dysplasia, particularly of the skin and skeletal system. Histopathology of the atrophic and lipomatous skin reveals marked reduction in the thickness of the dermis. Collagen fibers are attenuated and fat cells extend virtually up to the epidermis; thin strands of dermal connective tissue may be interspersed.[3]

Skin involvement is usually in the form of asymmetrical linear streaks of atrophy and telangiectasia, which follow Blaschko's lines. In racially pigmented skin, the lesions may be hypo or hyperpigmented. Soft, pinkish-yellow to brown saccular nodules (fat herniations) provide the second characteristic type of skin lesion.[3] These may appear any time after birth.[7] Other characteristic cutaneous findings include raspberry papillomas, present mostly at the junction of skin and mucosa, around lips, or the vulvar and perianal areas.[8] However, complete absence of skin in the form of aplasia cutis congenita has been reported rarely, which was the initial skin manifestation in our case. Now, aplasia cutis congenita (ACC) encompasses a heterogeneous group of disorders characterized by localized defects of skin that may occur anywhere on the body. Though the scalp is the most common site, it involved periumbilical area and the back of the thigh in this case.

Musculoskeletal anomalies include characteristic facies, as described in our case, and asymmetric involvement of the hands and feet in 60% of the patients, including syndactyly, ectrodactyly, polydactyly, absence or hypoplasia of digits, and even absence of an extremity. Clavicular dysplasia and spina bifida occulta can occur. The characteristic radiological change is osteopathia striata of the long bones.[10] Our patient had multiple skeletal anomalies like syndactyly, ectrodactyly and asymmetry of limbs with absence of multiple bones, both long and short, of the right lower limb. Other systems are also known to be frequently involved, of which gastro-intestinal and renal systems are of prime importance. There were a few reports about the presence of ectopic kidney,[11] hypoplastic kidney or absent kidney, but association of bilateral hydronephrosis and hydroureter is rarely reported in the literature.

The most common differential diagnoses are MIDAS (microphthalmia, dermal aplasia, sclerocornea), incontinentia pigmenti, Rothmund–Thomson syndrome, Adams–Oliver syndrome, nevus lipomatosus superficialis, aplasia cutis and Ectrodactyly Ectodermal dysplasia Clefting (EEC) syndrome. All these can be easily differentiated clinically by their characteristic phenotypes and features.[3]

So, to conclude, with timely diagnosis of complications and appropriate supportive care, majority of the patients can lead a normal life with adequate development and mentation, except a few unlucky ones with severe forms of affection.

What is new?

We are reporting a rare case of Goltz syndrome with aplasia cutis congenita as the initial cutaneous manifestation and bilateral hydronephrotic kidney, both of them being quite rare.