eMedicine Specialties > Dermatology > Pediatric Diseases

Rud Syndrome

Suguru Imaeda, MD, Chief of Dermatology, Yale University Health Services; Chief of Dermatology, West Haven Veterans Affairs Medical Center; Assistant Professor, Department of Dermatology, Yale University School of Medicine

Updated: Nov 30, 2007

Introduction

Background

Rud syndrome, previously considered a rare recessive disorder marked by ichthyosis, hypogonadism, mental retardation, epilepsy, and dwarfism, is now classified as an ichthyosis. The contemporary ichthyosis classification reassigns it as a neuroichthyosis with cutaneous findings most similar to those observed in X-linked recessive ichthyosis, rather than a distinct clinical entity. Although ichthyosis and hypogonadism are the predominant features, neurologic deficits vary, suggesting genetic heterogeneity.

Pathophysiology

The pathophysiology of Rud syndrome is unknown. Defects in steroid sulfatase and Kallmann loci on the X chromosome have been identified; however, these defects were not tested in most of the earlier cases. Cases suggestive of an autosomal recessive inheritance pattern have also been reported.

Frequency

International

The prevalence is rare worldwide.

Mortality/Morbidity

Mortality and morbidity depend on the presence and the severity of associated findings.

Race

No racial predilection is known.

Sex

Cases in which steroid sulfatase deficiency has been identified involved boys; however, overall, no male predilection is apparent, as anticipated by an X-linked recessive genodermatosis. This observation could be explained by the fact that a defect in an autosomal recessive gene may also be present (some cases suggestive of this inheritance pattern have been reported) or that such heterogeneity of clinical and genetic findings exists and some patients who are thought to have Rud syndrome really have different disorders manifesting with clinical changes similar to those of Rud syndrome.

Age

The disease manifests with clinical signs and symptoms at birth or shortly thereafter.

Clinical

History

• The most prominent feature of Rud syndrome is ichthyosis, which is congenital or present soon after birth.
• Neurologic findings are generally inconstant; however, mental retardation and epilepsy have been described in the literature as cardinal features.

Physical

• Ichthyosis has a predilection for the extensor extremities and can vary from a mild generalized branny desquamation to a severe flaky scaling that resembles snakeskin. Other cutaneous manifestations reported include acanthosis nigricans and alopecia.
• Skeletal defects include short stature, arachnodactyly, hypoplastic or absent teeth, and structural abnormalities of the hands and the feet.
• Neurologically, frequent seizures pose difficulty in long-term treatment. Other neurologic features include anosmia and hypertrophic polyneuropathy. Ophthalmologic defects include retinitis pigmentosa, strabismus, ptosis, blepharospasm, nystagmus, and cataracts.
• Hypogonadism, which may be primary or hypogonadotrophic in origin, is more easily recognized in males who tend to be eunuchoid in appearance. Eunuchoid features include thin, soft, pale skin, which is not oily because the sebaceous glands and apocrine glands are dormant; absent secondary sexual characteristics, such as a small penis, poorly furrowed scrotal skin, and lack of beard, axillary, and pubic hair; straight hairline over the forehead and low hairline over the temples; poor muscle development; excessive subcutaneous fat in the pectoral and girdle regions; and long arms and legs secondary to delayed closure of the epiphyses, with resultant prolonged growth of the long bones.

Causes

• Genetic mutations are the cause; both autosomal recessive inheritance and X-linked recessive inheritance have been reported.
• A genetic defect may be a cause. Although unknown, the genetic defect is suspected to involve a deletion of the steroid sulfatase locus.
• The heterogeneity of the genetic abnormalities may account for the presence of X-linked ichthyosis–like skin changes in male and female patients.

Differential Diagnoses

Ichthyosis Vulgaris, Hereditary and Acquired
Ichthyosis, X-Linked

Other Problems to Be Considered

Pituitary hypogonadism
Anosmia

Workup

Laboratory Studies

• Steroid sulfatase deficiency has been reported in some cases of Rud syndrome.

Other Tests

• Electroencephalography should be performed as appropriate for evaluation of seizures.

Histologic Findings

Histologic findings may include nonspecific changes demonstrated by light and electron microscopy.

Treatment

Medical Care

• Ichthyosis and acanthosis nigricans can be treated with alpha hydroxy acids (eg, ammonium lactate, glycolic acid) and urea to improve cosmetic appearance.
• Epileptic seizure treatment is the most difficult aspect of therapy.

Surgical Care

Surgical therapy of associated ophthalmologic problems may be indicated.

Consultations

• Consultation with a neurologist is needed for seizure management.
• Consultation with a developmental specialist is needed for mental retardation.
• Consultation with an endocrinologist is needed for possible pituitary hypogonadism.
• Consultation with an ophthalmologist is needed for possible retinitis pigmentosa, strabismus, ptosis, blepharospasm, cataract, and nystagmus.
• Consultation with a genetic counselor may be obtained as appropriate.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Keratolytics

These agents promote shedding of hyperkeratotic skin. They are modifiers of keratinocyte adhesion, differentiation, and proliferation.

Ammonium lactate lotion (AmLactin, Lac-Hydrin)

Contains lactic acid, an alpha hydroxy acid with keratolytic action. Comes in 12% and 5% strengths. The 12% concentration may cause irritation on the face. Causes disadhesion of corneocytes.

Dosing

Adult

Apply topically to lesion or liberally to all affected areas bid for xerosis or other dry skin conditions

Pediatric

Apply as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May sting or cause pain if applied on broken skin; the 12% concentration may cause irritation with erythema, burning, and peeling if applied to the face

Glycolic acid

Alpha hydroxy acid with keratolytic action.

Dosing

Adult

Apply to affected areas prn

Pediatric

Apply as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May sting or cause pain if applied on broken skin; for external use only

Urea (Ureaphil, Ureacin-40, Aquacare)

Promotes hydration and removal of excess keratin in conditions of hyperkeratosis. Available in 10-40% concentrations.

Dosing

Adult

Apply to affected areas prn

Pediatric

Apply as in adults

Interactions

May decrease effects of lithium

Contraindications

Documented hypersensitivity; severely impaired renal function; active intracranial bleeding; marked dehydration; frank liver failure; infusion into lower extremity veins in elderly patients may cause phlebitis and thrombosis

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use if intracranial bleeding is present, unless prior to surgical intervention to control hemorrhage (reduction of brain edema by urea may result in reactivation of intracranial bleeding); may increase risk of venous thrombosis and hemoglobinuria in patients with hypothermia; caution in renal impairment

Follow-up

Further Outpatient Care

• Neurologic follow-up care for seizure management is indicated.

Inpatient & Outpatient Medications

• Anticonvulsants and keratolytics are the inpatient and outpatient medications.

Prognosis

• The heterogeneity of the clinical findings in patients with Rud syndrome makes predicting the prognosis impossible. The prognosis varies depending on the type and the severity of associated findings.

Patient Education

• Patients may seek genetic counseling as appropriate.

Miscellaneous

Medicolegal Pitfalls

• Failure to identify and properly treat associated findings is a pitfall.

References

1. Andria G, Ballabio A, Parenti G, Di Maio S, Piccirillo A. Steroid sulphatase deficiency is present in patients with the syndrome 'ichthyosis and male hypogonadism' and with 'Rud syndrome'. J Inherit Metab Dis. 1984;7 Suppl 2:159-60. [Medline].

2. Kaufman LM. A syndrome of retinitis pigmentosa, congenital ichthyosis, hypergonadotropic hypogonadism, small stature, mental retardation, cranial dysmorphism, and abnormal electroencephalogram. Ophthalmic Genet. Jun 1998;19(2):69-79. [Medline].

3. Larbrisseau A, Carpenter S. Rud syndrome: congenital ichthyosis, hypogonadism, mental retardation, retinitis pigmentosa and hypertrophic polyneuropathy. Neuropediatrics. May 1982;13(2):95-8. [Medline].

4. Maldonado RR, Tamayo L, Carnevale A. Neuroichthyosis with hypogonadism (Rud's syndrome). Int J Dermatol. Jun 1975;14(5):347-52. [Medline].

5. Marxmiller J, Trenkle I, Ashwal S. Rud syndrome revisited: ichthyosis, mental retardation, epilepsy and hypogonadism. Dev Med Child Neurol. Jun 1985;27(3):335-43. [Medline].

6. Münke M, Kruse K, Goos M, Ropers HH, Tolksdorf M. Genetic heterogeneity of the ichthyosis, hypogonadism, mental retardation, and epilepsy syndrome. Clinical and biochemical investigations on two patients with Rud syndrome and review of the literature. Eur J Pediatr. Oct 1983;141(1):8-13. [Medline].

7. Stoll C, Eyer D. A syndrome of congenital ichthyosis, hypogonadism, small stature, facial dysmorphism, scoliosis and myogenic dystrophy. Ann Genet. 1999;42(1):45-50. [Medline].

8. Sybert VP. Ichthyosis with hypogonadism. In: Genetic Skin Disorders. ed. New York, NY: Oxford University Press; 1997:114-5.

9. Tercedor J, García A. [Keratotic neurocutaneous syndromes]. Rev Neurol. Sep 1997;25 Suppl 3:S238-42. [Medline].

10. Kuniba H, Egashira M, Motomura H, Motomura K, Kondoh T. [Rud syndrome]. Nippon Rinsho. Sep 28 2006;Suppl 3:485-7. [Medline].

Keywords

ichthyosis with hypogonadism, neuroichthyosis, ichthyosis, hypogonadism, mental retardation, epilepsy, dwarfism

Contributor Information and Disclosures

Author

Suguru Imaeda, MD, Chief of Dermatology, Yale University Health Services; Chief of Dermatology, West Haven Veterans Affairs Medical Center; Assistant Professor, Department of Dermatology, Yale University School of Medicine
Suguru Imaeda, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Connecticut State Medical Society, Sigma Xi, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Mark A Crowe, MD, Assistant Clinical Instructor, Department of Medicine, Division of Dermatology, University of Washington School of Medicine
Mark A Crowe, MD is a member of the following medical societies: American Academy of Dermatology and North American Clinical Dermatologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other

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