Bloch-Sulzberger Syndrome: Causes, Symptoms, Treatment, Complications, Pathophysiology
Bloch-Sulzberger syndrome is a genetic disorder that affects the skin, hair, teeth and the central nervous system. It is an x-linked dominant genetic disorder due to mutation of IKBKG gene (formerly known as NEMO). Bloch-Sulzberger syndrome was first described by Garrod in 1906, and was later further defined by Bloch and Sulzberger in 1926 and 1928 respectively. Bloch-Sulzberger syndrome is characterized by blisters on the trunk and limbs that develop soon after birth. The blisters heal gradually, but leave behind areas of hyperpigmentation over the skin. It is popularly known as Incontinentia Pigmenti due to the characteristic appearance of skin when observed through a microscope. Bloch-Sulzberger syndrome is also known by other terminologies such as:
- Bloch-Siemens incontinentia pigmenti melanoblastosis cutis linearis.
- Pigmented dermatosis, Siemens-Bloch type.
Bloch-Sulzberger syndrome is often associated with other conditions such as DIRA (Interleukin 1 receptor antagonist deficiency); Incontinentia Pigmenti achromians; Franceschetti-Jadassohn syndrome; Caffey disease etc.
Symptoms of Bloch-Sulzberger Syndrome
- Skin Issues in Bloch-Sulzberger Syndrome: The skin symptoms are the most common characteristics of Bloch-Sulzberger syndrome. These symptoms appear as lesions in linear pattern on the arms and legs and in a swirled pattern over the trunk. The skin symptoms usually proceed in the following stages:
- Stage 1 Skin Symptoms of Bloch-Sulzberger Syndrome: This is characterized by redness, inflammation, blisters and boils over the extremities or the scalp that may last for a few weeks, a few months or a year intermittently.
- Stage 2 Skin Symptoms of Bloch-Sulzberger Syndrome: In this stage, the blisters develop into a raised wart-like lesion with thick crusts and scabs. There are increased areas of darkened skin or hyperpigmentation.
- Stage 3 Skin Symptoms of Bloch-Sulzberger Syndrome: This appears between the ages of 6 to 12 months. There is further increase in hyperpigmentation. There may be an area of darkened skin on the trunk giving the appearance of "marble cake."
- Stage 4 Skin Symptoms of Bloch-Sulzberger Syndrome: This is a stage that is also known as the atrophic stage. The scar starts to fade away. During adolescence the faded scars appears as pale and hairless patches or streaks. As the individuals reaches adulthood, the scars and areas of hyperpigmentation fades away.
- Dental Problems in Bloch-Sulzberger Syndrome: The most commonly encountered dental issues include delay in eruption of primary teeth, peg-shaped or cone-shaped anterior teeth, absence of teeth (anodontia) or appearance of small sized teeth (microdontia).
- Hair Loss as a Symptom of Bloch-Sulzberger Syndrome: Patients affected by Bloch-Sulzberger syndrome may have bald patches and alopecia. The hair generally appears wiry, coarse with lack of lustre.
- Eyes Problems in Bloch-Sulzberger Syndrome: Children with Bloch-Sulzberger syndrome may be born with a small abnormal eye. There may be retinal abnormalities, which if left untreated can lead to serious complications.
- Neurological Issues in Bloch-Sulzberger Syndrome: Neurological involvement in Bloch-Sulzberger syndrome is rare. However, in few cases there may be congenital or neonatal stroke as a result of Bloch-Sulzberger syndrome. Some patients may also experience electrical disturbances in the brain, seizures, muscle weakness, learning difficulties etc.
- Other Abnormalities in Bloch-Sulzberger Syndrome: Females affected by Bloch-Sulzberger syndrome may be born with physical abnormalities such as extra nipples or complete absence of breasts.
Epidemiology of Bloch-Sulzberger Syndrome
Bloch-Sulzberger syndrome is a rare disease and only about 700 cases have been reported worldwide up until 1987. It has a worldwide distribution and more cases have been reported among the whites than in blacks or Asians. Bloch-Sulzberger syndrome being an X-linked dominant syndrome, it is more common in females. It occurs very rarely in males in association with other genetic conditions such as Klinefelter syndrome (XXY syndrome), somatic mosaicism or hypomorphic mutation in NEMO gene. The female:male ratio is 20:1. The birth prevalence is at 0.65/1000000 population as per the public health birth defect surveillance system.
Causes and Pathophysiology of Bloch-Sulzberger Syndrome
Bloch-Sulzberger syndrome is a type of ectodermal dysplasia with abnormalities in the tissues and organs derived from neuro-ectoderm and ectoderm. It is a genetic disorder caused by x-linked dominant genodermatosis. It is caused by mutation of the IKBKG gene or the NEMO gene, which is responsible for production of a specific protein that helps is providing protection to cells and prevents self-destruction. This condition presents itself with neurologic and ophthalmological anomalies in addition to involvement of hair, teeth, nails and skin. It has been noted that in females affected by this disorder, there is lyonization which leads to functional mosaicism of X-linked genes which presents itself as blaschkoid distribution of cutaneous lesions. Females with Bloch-Sulzberger syndrome have extreme skewed X-inactivation pattern as the cells that express the mutated X chromosomes selectively eliminate during the birth time. The affected skin has abnormal chromosomes and the unaffected skin has normal chromosomes.
Complications of Bloch-Sulzberger Syndrome
The most serious complication of Bloch-Sulzberger syndrome is retinal detachment. If eye issues are not treated in the early stages, it can lead to visual impairment and even permanent blindness. Neurological complications include slow motor development, intellectual disability, muscle weakness and seizures. In rare cases, there may be abnormalities with breast development such as extra nipples or absence of breast.
Diagnosis of Bloch-Sulzberger Syndrome
In addition to clinical examination and detailed case history, the diagnosis of Bloch-Sulzberger syndrome involves molecular genetic testing to confirm mutation of IKBKG gene. A skin biopsy is usually helpful in borderline cases or in cases of unclear findings in gene testing. Regular eye examination by a paediatric ophthalmologist is recommended in children suspected to be affected by Bloch-Sulzberger syndrome. Physical examination is predominantly emphasized on skin, hair, nails and neurological examination. Electroencephalography (EEG), magnetic resonance imaging (MRI) and magnetic resonance angiography may be considered based on the extent of the disease. It is advised to the mother to consult a geneticist and a dermatologist for an in depth evaluation, after a child is born with Bloch-Sulzberger syndrome.
Treatment of Bloch-Sulzberger Syndrome
The treatment modality for Bloch-Sulzberger syndrome is planned based on the symptoms elicited by the patient. Treatment for Bloch-Sulzberger syndrome is usually symptomatic and supportive. The skin abnormalities in Bloch-Sulzberger syndrome patients usually resolve by itself and do not require any treatment. In cases of retinal detachment predisposed by neovascularization, cryotherapy and laser photocoagulation may be done. Dental issues are treated by a dentist; this may require fabrication of implants based on the oral condition. Consultation with speech pathologist and paediatric nutritionist may be required if the patient suffers from speech and chewing difficulties. Hair issues may require dermatological treatment. Oral medications are often recommended for management of neurological conditions such as seizures, mild paralysis and muscle spasms. It is advised to the patient and his family to get a genetic counseling done.
Prevention of Bloch-Sulzberger Syndrome
Precautionary steps include genetic counseling prior to planning pregnancy particularly in presence of family history of genetic abnormalities. It is also advised to get an eye examination done on a regular basis in patients affected by this condition to prevent complications in the eyes.
Bloch-Sulzberger syndrome is a rare congenital disorder caused by X-linked dominant genetic disorder. It is more common in females than in males. It is characterized by skin abnormalities that arise soon after birth and gradually resolves with increase in age. The treatment aims at symptomatic management of the symptoms of Bloch-Sulzberger syndrome. In cases of retinal detachment, cryosurgery and laser treatment may be considered. Intervention by a speech specialist and nutritionist may be required based on symptoms of Bloch-Sulzberger syndrome. Genetic counseling is recommended to the patient and the family for in-depth analysis and evaluation. Although, not a life-threatening condition for females, prevention of retinal detachment is the main objective and hence all preventive measures must be taken.