Introduction 

Focal dermal hypoplasia also referred to as Goltz syndrome may be something you’ve never heard of and this is because it is a rare multisystem genetic disorder typically affecting the skin, eyes, hands, feet and teeth, as well as other organ systems such as the cardiovascular, neurological and gastroenterological systems.¹ 

As identified by Goltz in 1962 the disorder is inherited in an X-linked dominant fashion but there have been some cases where the disorder is not inherited but occurs from a mutation as an embryo. The genetic cause is the PORCN gene mutation on the X chromosome, 90 % of affected individuals are female. Whereas, as males only have one X chromosome and one Y chromosome, this mutation is usually lethal for them or they will only present with the mutation in some of their cells which is known as mosaicism so this variant may only present with mild symptoms.²  

Focal dermal hypoplasia presents with various characteristic findings and recognition of them is important for clinical diagnosis.^3,4 In this article, we will break down different symptoms of Focal dermal hypoplasia.

What are the symptoms of focal dermal hypoplasia?

Focal dermal hypoplasia manifests in various ways and can present with different severities depending on the individual, number of organs involved and the type of abnormality. There are certain subsets of symptoms that are characteristic of diagnosing this disorder and can be split up into skin manifestations, ocular features, skeletal abnormalities, dental anomalies and other clinical features.⁵

Skin Manifestations

These can be present at birth and can also be known as ectodermal manifestations. For a clinician, it is important to note that all individuals diagnosed with Focal dermal hypoplasia will have one or more skin manifestations and so it is considered a hallmark symptom. 

The most common skin-related symptoms include:

• Linear atrophic or hypoplastic skin areas which follow Blaschko’s lines: This is where the skin may be thin or lacking in colour. They are linear to Blaschko’s lines which are lines of cell migration and form different shapes dependent on the area of the body. On the abdomen, the lines are a S- shape, on the upper spine they are a V shape and from the breast to the upper arms they appear as an inverted U. These hypoplastic skin areas which follow Blaschko’s lines are evident at birth but over time they may change in distribution and severity. A patient may describe these skin changes as ‘pink or white streaks’ or areas of skin that appear depressed and undeveloped⁵
• Blistered and ulcerated skin; Patients may experience increased inflammation and redness of the skin. The blistering and ulceration may form skin crusting and can be painful¹
• Telangiectasia: As the child gets older, the capillaries and veins under the skin become more visible. It may be present in areas like the hands, feet, trunk and face²
• Fat herniation and nodules: They appear as soft yellow/ pink skin nodules and can be found on the trunk, hands or feet³
• Papillomatosis: Wart-like growths, not present at birth but develop with age. Common location sites are mucous membranes which include the mouth, pharynx, larynx, nose, gums, tongue, lips, oesophagus, nose, genitals and anus. If larynx papillomas are too large they can obstruct breathing and cause obstructive sleep apnea⁵
• Pyogenic granuloma-like growths: small red bumps which can bleed easily 
• Thickened skin on hands and feet 
• Aplasia cutis congenita which is absent skin layers or total loss of skin
• Increased skin sensitivity to UV light (photosensitivity)
• Excessive sweating is known as Hyperhidrosis²

The skin forms a part of the integumentary system which also includes the hair and nails which can be affected by Focal dermal hypoplasia: 

Nails 

• Nails may be absent 
• Abnormal congenital nails: they may be small, ridged, dysplastic, hypoplastic, split or have V-shaped nicking⁵

Hair

• It may be a wiry or brittle texture 
• Patchy alopecia or sparse hair³

Ocular Features

Ocular refers to your eyes and this is a key organ that is affected in Focal Dermal Hypoplasia. They are common abnormalities and usually present at birth. 

Symptoms can include:

• Ptosis: Drooping eyelids 
• Small or absent eyes 
• A wide space between the eyes 
• Crossed eyes and involuntary eye movement 
• Exposed eyelid lining¹
• Colobomas are defects or absence of eye structures like the retina, choroid, iris, and optic nerve that can cause visual impairment 
• Blocked tear ducts⁶
• Clouding of the cornea 
• Displaced lens 
• Cataracts³

Skeletal Abnormalities

The disorder can also impact the skeletal system and clinical presentation of this includes: 

• Spinal issues: Scoliosis or kyphosis- This can be mild to severe curvature of the spine
• Hand and Foot abnormalities: Additional, undeveloped, missing or fused toes or fingers. They also may have a claw-like appearance, they may bend to the side or may have a permanent curvature²
• Transverse limb defect: meaning there could be an absence of a body part 
• Shortening of the long bones is known to cause leg length discrepancy 
• Vertebral deformities: Fused or split ribs, a wedge -shaped or butterfly vertebrae.
• Abnormal separation of the pubic bones
• Bone problems include Fibrous dysplasia of bone, where normal bone is replaced by fibrous tissue, Giant cell tumours of long bones and the development of a striated appearance of bones.(Osteopathia striata)⁵
• Craniofacial abnormalities include asymmetry of the face, a smaller than usual head, an undeveloped head or jaw, a pointed jaw, a small underfolded pinna which is an external ear abnormality, notched appearance to the outer portion of the nostrils, low set ears and even cleft lip/palate¹

Dental Anomalies

In more than 50 % of individuals with Focal Dermal Hypoplasia, mouth and dental anomalies are seen. These are: 

• Undeveloped or missing teeth 
• Small and incorrectly spaced teeth 
• Teeth with reduced or missing enamel make individuals prone to developing cavities¹
• Extra teeth on the lower, upper jaw or both
• Abnormally shaped teeth may be prism-shaped 
• Teeth that are fused together 
• Problems with the form, shape and structure of a tooth root may lead to incorrect positioning or delayed eruption of teeth⁵

Soft tissue abnormalities of the oral cavity include: 

• Generalised gingivitis - this is early-stage gum disease characterised by red, bleeding or swollen gums⁷
• Papillomas or lipomas⁵

Additional Symptoms

Other organ systems can also be affected by this disorder as listed below: 

Gastrointestinal and nutrition 

• Poor weight gain and the patient may be small at birth 
• Feeding, chewing and oral motor swallowing problems 
• Gastroesophageal reflux disease can be due to oesophageal papillomas. Presents as irritation and vomiting
• Food allergies 
• Constipation 
• Structural defects: abdominal organs found outside the stomach, a twisted bowel, an anterior displacement of the anus 
• Hernias 
• Gastroparesis which is a delay in gastric emptying⁸

Renal and genitourinary 

• In females there is Genital labial hypoplasia, which is where both or one of the labia don’t form normally during puberty 
• Uterine malformations 
• Split ureter 
• Structural kidney defects: Horseshoe kidney, a missing kidney, a swollen kidney 
• Bladder defects: Inside-out bladder⁹

Cognitive and psychological 

• In most individuals, development and intelligence are normal but in some individuals, this may be impaired
• Behavioural and emotional issues: exaggerated and strong mood or emotions or may have withdrawn behaviour
• Seizures are rare⁸

Other abnormalities regarding the neurological and cardiovascular system have been reported but are more uncommon.¹

Summary

Outlining the most commonly seen symptoms and clinical presentations of Focal Dermal Hypoplasia is important as diagnosis depends on this. The symptoms can be split up into different organ systems including the skin, skeletal system, eyes, mouth, gastrointestinal, renal and urogenital and cognitive. As it is a genetic disorder, symptom severity depends on factors like tissue mosaicism and penetrance which is usually high in females. Treatment for Focal Dermal Hypoplasia is categorised based on the specific manifestations and the role of a dermatologist is especially important in monitoring and managing the skin findings which is a hallmark that is present in all individuals affected. Overall Focal Dermal Hypoplasia is a rare disease and there are still clinical studies and genetic counselling such as family planning that is underway to manage this disorder.⁸