Challenging Cases in Dermatology Volume 2: Advanced Diagnoses and Management Tactics

By Mohammad Ali El-Darouti and Faiza Mohamed Al-Ali

This book comprehensively covers a range of challenging cases in dermatology. It provides easy to follow guidance on how to successfully diagnose and treat a range of unusual diseases with a range of figures with informative legends and clinical data focused exercises to enable the reader to gain confidence and a deep understanding of why the diagnostic and treatment procedures taken in each case were chosen. Cases covered include follicular disorders, melanocytic diseases, vascular tumors, cutaneous lymphomas, and bullous diseases. 

This second volume of Challenging Cases in Dermatology systematically describes a range of unusual and rare clinical cases in dermatology. It is therefore a valuable resource for all trainee and practising dermatologists looking to further develop their knowledge and understanding of how to successfully diagnose and treat rare and challenging diseases. 

• Language: English
• Publisher: Springer
• Release date: Aug 28, 2019
• ISBN: 9783030218553

Book preview

Part IAtrophic Skin

© Springer Nature Switzerland AG 2019

M. A. El-Darouti, F. M. Al-AliChallenging Cases in Dermatology Volume 2https://doi.org/10.1007/978-3-030-21855-3_1

1. Neck Scarring, with Defects of Ears and Eyes

Mohammad Ali El-Darouti¹  and Faiza Mohamed Al-Ali²

(1)

Faculty of Medicine, Cairo University, Cairo, Egypt

(2)

Dubai Health Authority, Rashid Hospital, Dubai, United Arab Emirates

Keywords

CervicalLinear scarringAutosomal dominantEar deformitiesPreauricular pitsBroad nasal rootColobomasOcular anomaliesCleft lip and palateRenal anomalies

Clinical Data (Figs. 1.1, 1.2, 1.3, and 1.4)

A 33 YO female presented with :

Ear changes including deformed, low set, posteriorly rotated ears, anteverted ear lobules, narrow external auditory canal, and preauricular pits.

Microophthalmia, coloboma, strabismus, broad nasal route.

Bilateral cervical scarring.

History revealed similarly affected sister (Fig. 1.5) with facial and neck scarring, bilateral ear anomalies, cleft lip, and broad nose.

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Figs. 1.1, 1.2, 1.3, and 1.4

A Female with a deformed ear, broad nasal root, with face and neck scarring

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Fig. 1.5

The patient's sister, with extensive neck scarring

Differential Diagnosis

Syndromes showing combinations of ear, eye, nose, and neck abnormalities include:

CHARGE syndrome :

CHARGE = (coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities).

Coloboma and ear abnormalities are present in our patient; however, other features of CHARGE syndrome are absent.

Branchio-Oto-Renal syndrome (BORS) :

An autosomal dominant disorder characterized by sensorineural, conductive, or mixed hearing loss, structural defects of the outer, middle, and inner ear, branchial fistulas or cysts, and renal abnormalities ranging from mild hypoplasia to complete absence.

BORS shows no cleft lip or palate, and no cervical skin anomalies.

Branchio – Oculo – Facial syndrome (BOFS):

Shows all the features presented in our patient (eye and ear anomalies, neck scarring and broad nose).

Investigations

Lab investigations :

No findings.

Radiological investigations :

Abdominal ultrasonography was normal.

Biopsy Findings (Fig. 1.6)

Biopsy from scarred skin of the neck showed; atrophic skin, scarred dermis and absent skin appendages.

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Fig. 1.6

Atrophic skin, scarred dermis, and absent skin appendages

Based on the Following Findings

The clinical features of:

Bilateral cervical linear scarring.

Ear deformities.

Eye and nose abnormalities.

The Final Diagnosis was

Branchio – Oculo – Facial syndrome (BOFS)

About the Diagnosis

Definition

Branchio-oculo-facial syndrome (BOFS) is a rare, autosomal dominant disorder of the first and second branchial arches.

It was first described by Lee et al. in the early 1980s.

It features distinct craniofacial abnormalities including an abnormal location of the ears, aplastic cervical skin lesions, malformed auricles, conductive hearing loss, ocular anomalies, and cleft lip and palate.

Epidemiology

BOFS is a rare condition , although the prevalence is unknown.

About 90 cases of BOFS had been reported in the medical literature.

It affects males and females in equal numbers.

Pathogenesis and Etiology

BOFS is inherited as an autosomal dominant disorder with incomplete penetrance and variable expression.

It is caused by mutations involving the TFAP2A gene on chromosome 6, which is one of the AP-2 family of transcription factors.

This gene has been shown to regulate the development of facial prominences, limb buds, cranial closure, and the lens vesicle.

Clinical Features

The followings are distinctive features of BOFS:

Ocular:

Nasolacrimal duct stenosis.

Strabismus.

Coloboma.

Auricular:

Malformed external ear.

Preauricular pits.

Nasal:

Broad nasal bridge.

Craniofacial:

Cleft lip and palate.

Neck anomalies:

Bilateral linear cervical scarring.

Extracranial anomalies:

Renal anomalies (common).

Cardiac anomalies (rare).

Histological Features

Biopsy of the neck scarring lesion shows atrophic skin, scarred dermis, and absent skin appendages.

Investigations

Abdominal ultrasonography for renal anomalies .

Echocardiography.

Differential Diagnosis

CHARGE syndrome: (coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities). Coloboma and ear abnormalities are present in our patient; however, other features of CHARGE syndrome are absent.

Branchio – Oto –Renal syndrome (BORS). Both BORS and BOFS can be associated with nasolacrimal duct stenosis, hearing loss, and renal anomalies. However, the clinical features such as cleft lip and palate, pseudocleft of the lip, and aplastic skin are not found in BORS. Besides, the responsible genes for the two syndromes appear to be different.

Definite Diagnosis

Diagnosis is based on the clinical features of:

Bilateral cervical linear scarring.

Ear deformities.

Eye and nose abnormalities.

Genetic study for identification of the mutated gene is not usually performed .

Treatment

Treatment of BOFS is aimed at specific signs and symptoms.

Reconstructive surgery to repair facial deformities and obstructed nasal ducts is usual (otorhinolaryngology consultation/Maxillofacial/plastic surgery).

Crossed eyes may also be corrected by surgery.

Genetic counseling is recommended for patients and their families as there is 50% inheritance.

Management of This Case

The patient was referred to plastic for reconstructive surgery.

../images/469075_1_En_1_Chapter/469075_1_En_1_Figa_HTML.jpg Message

A high index of suspicion is needed when a patient presents with clinical features suggesting branchio-oculo-facial syndrome (BOFS).

Think of BOFS when you see a patient with a broad nasal route, eye changes, ear deformities, and bilateral neck scarring.

Although it is very rare, physicians should be aware of the features of BOFS due to the impact of the associated anomalies.

Bibliography

1.

Bennaceur S, Buisson T, Bertolus C, Couly G. Branchio-oculo-facial syndrome with cleft lip and bilateral dermal thymus. Cleft Palate Craniofac J. 1998;35:454–9.Crossref

2.

El Darouti MA, Marzouk SA, Azzam OA, Nada HR, Sobhi RM, El Nabarawi I. Branchio-oculo-facial syndrome with bilateral linear scars of the neck. Int J Dermatol. 2005;44:674–6.Crossref

3.

Fujimoto A, Lipson M, Lacro RV, Shinno NW, Boelter WD, Jones KL, et al. New autosomal dominant branchio-oculo-facial syndrome. Am J Med Genet. 1987;27:943–51.Crossref

4.

Hall BD, deLorimier A, Foster LH. Brief clinical report: a new syndrome of hemangiomatous branchial clefts, lip pseudoclefts, and unusual facial appearance. Am J Med Genet. 1983;14:135–8.Crossref

5.

Hiroshi F, Satoru S, Eisuke U, Kunihiro K, Yuhei Y. Bilateral dermal thymus of neck in branchio-oculo-facial syndrome. J Plast Reconstr Aesthet Surg. 2006;59:1385–7.Crossref

6.

Kapoor S, Kapur N. Branchio-oculo-facial syndrome with valvular pulmonic stenosis. Indian Pediatr. 2004;41:1180–1.PubMed

7.

Kulkarni ML, Deshmukh S, Kumar A, Kulkarni PM. Branchio-oculo-facial syndrome. Indian J Pediatr. 2005;72:701–3.Crossref

8.

Lee WK, Root AW, Fenske N. Bilateral branchial cleft sinuses associated with intrauterine and postnatal growth retardation, premature aging, and unusual facial appearance: a new syndrome with dominant transmission. Am J Med Genet. 1982;11:345–52.Crossref

9.

Lin AE, Gorlin RJ, Lurie IW, Brunner HG, van der Burgt I, Naumchik IV, et al. Further delineation of the branchio-oculo-facial syndrome. Am J Med Genet. 1995;56:42–59.Crossref

10.

Megarbane A, Hawat N, Chedid P, Bleik J, Delezoide AL. Branchio-oculo-facial syndrome associated with a white forelock. Clin Dysmorphol. 1998;7:221–3.Crossref

11.

Milunsky JM, Maher TA, Zhao G, Roberts AE, Stalker HJ, Zori RT, et al. TFAP2A mutations result in branchio-oculo-facial syndrome. Am J Hum Genet. 2008;82:1171–7.Crossref

12.

Ozturk O, Tokmak A, Demirci L, Silan F, Guclu E. Branchio-oculo-facial syndrome with the atresia of external ear. Int J Pediatr Otorhinolaryngol. 2005;69:1575–8.Crossref

13.

Park MY, Kim YC. A case of Branchio-oculo-facial syndrome. Ann Dermatol. 2009;21(3):288–90. https://​doi.​org/​10.​5021/​ad.​2009.​21.​3.​288.CrossrefPubMedPubMedCentral

14.

Raveh E, Papsin BC, Forte V. Branchio-oculo-facial syndrome. Int J Pediatr Otorhinolaryngol. 2000;53:149–56.Crossref

15.

Rosa RF, Zen PR, Graziadio C, Paskulin GA. Branchio-oculo-facial syndrome (BOFS) and congenital heart defects. Arq Bras Cardiol. 2009;92:e6–8.Crossref

16.

Stoetzel C, Riehm S, Bennouna Greene V, Pelletier V, Vigneron J, Leheup B, Marion V, Helle S, Danse JM, Thibault C, Moulinier L, Veillon F, Dollfus H. Confirmation of TFAP2A gene involvement in branchio-oculo-facial syndrome (BOFS) and report of temporal bone anomalies. Am J Med Genet A. 2009;149A:2141–6.Crossref

17.

Su CS, O'Hagen SB, Sullivan TJ. Ocular anomalies in the branchio-oculo-facial syndrome. Aust N Z J Ophthalmol. 1998;26:43–6.PubMed

© Springer Nature Switzerland AG 2019

M. A. El-Darouti, F. M. Al-AliChallenging Cases in Dermatology Volume 2https://doi.org/10.1007/978-3-030-21855-3_2

2. Loss of Subcutaneous Fat, Muscle Hypertrophy, Diabetes and Hyperlipidemia

Mohammad Ali El-Darouti¹  and Faiza Mohamed Al-Ali²

(1)

Faculty of Medicine, Cairo University, Cairo, Egypt

(2)

Dubai Health Authority, Rashid Hospital, Dubai, United Arab Emirates

Keywords

Genetic syndromeLoss of subcutaneous fatMuscle hypertrophyHyperglycemiaHyperlipidemiaHepatosplenomegalyLipodystrophyEarly onsetLeptin treatment

Clinical Data (Figs. 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, and 2.7)

A 13 YO male presented with loss of subcutaneous fat on the face and extremities, in addition to the following features, mostly noted shortly after birth:

Protruded abdomen, muscle hypertrophy, prominent subcutaneous veins.

Short stature.

Mildly enlarged hands and feet (acromegaloid features).

Low mentality.

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Figs. 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, and 2.7

A 13 YO male with loss of subcutaneous fat on the face and extremities, protruded abdomen, muscle hypertrophy, prominent subcutaneous veins. He also had relatively enlarged hands and feet (acromegaloid features). Arrows are pointing at areas of fat loss

Differential Diagnosis

Syndromes with loss of subcutaneous fat include:

Lawrence syndrome :

It features all of the findings in our patient.

However, Lawrence syndrome is an acquired condition occurring in adulthood.

Leprechaunism (Donohue syndrome ):

It is characterized by loss of subcutaneous fat.

Additional features of Donohue syndrome include large low set ears, widely spaced eye, and marked weakness leading to early death in the first few months of life.

Berardinelli Seip congenital lipodystrophy syndrome:

It features all the findings in our patient.

There are no findings in our case against this diagnosis.

Investigations

Lab investigations :

Hyperglycemia.

Hyperlipidemia.

Radiological investigations :

Abdominal ultrasonography: hepatosplenomegaly.

Echocardiography: no abnormalities.

Biopsy Findings

Skin biopsy revealed absence of the subcutaneous fat.

Based on the Following Findings

Loss of subcutaneous fat.

Muscle hypertrophy.

Hyperglycemia and hyperlipidemia.

Hepatosplenomegaly.

Early onset of symptoms.

The Final Diagnosis was

Berardinelli-Seip Congenital Lipodystrophy (BSCL)

About the Diagnosis

Definition

Berardinelli-Seip Congenital Lipodystrophy (BSCL) or Berardinelli-Seip syndrome is a rare autosomal recessive disease, characterized by the following features :

Loss of subcutaneous fat.

Muscle hypertrophy.

Hyperglycemia and hyperlipidemia.

Hepatomegaly and splenomegaly.

It was first described in 1954 by Berardinelli, in a 2-year-old boy in Brazil. Later in 1959, Seip described the same syndrome in three other patients.

Epidemiology

BSCL is a rare syndrome with an estimated prevalence of 1 in every 10 million births.

Until date, only 300 cases have been reported.

Both male and female are equally affected.

It’s present at birth or during early infancy.

Pathogenesis and Etiology

BSCL is inherited as an autosomal recessive trait, with frequent parental consanguinity.

It is caused by mutation of any of the following genes:

BSCL2.

AGPAT2.

CAVI 1.

PTRF.

At least three molecularly distinct forms of BSCL have been defined, with the mutations of AGPAT2 and BSCL2 being responsible for 95% of reported cases.

Gene mutation leads to Leptin deficiency (a hormone synthesized in lipocytes), resulting in:

Loss of subcutaneous fat.

Accumulations of fat in the liver causing hepatomegaly and cirrhosis, and in muscles leading to muscle hypertrophy.

Clinical Features

BSCL is mostly diagnosed at birth or soon after that. Severe forms of BSCL may have prenatal onset with intrauterine growth retardation.

Presentation in the first months of life includes failure to thrive (or conversely gigantism), hepatomegaly, lipoatrophy, facial dysmorphia, enlarged tongue, or developmental delay.

All children with the neonatal or infantile presentation demonstrate lipoatrophy in the first year of life.

Affected adults may first be seen in the plastic surgery clinic seeking cosmetic improvement of facial lipoatrophy or in the cardiology clinic or gastroenterology clinic for manifestations such as hypertrophic cardiomyopathy or hepatomegaly.

Endocrine findings:

Insulin resistance. Approximately 30% of individuals develop diabetes mellitus, mostly between the ages of 15 and 20 years.

Some women present with oligomenorrhea, amenorrhea, or features of polycystic ovary syndrome.

Hypertrophic cardiomyopathy (a significant cause of morbidity and mortality).

Hepatomegaly secondary to hepatic steatosis occurs in virtually all individuals with BSCL.

Intellectual impairment is common.

Skeletal muscle hypertrophy occurs in all affected individuals as a result of lipid storage in skeletal muscle.

Table 2.1 summarizes the diagnostic criteria of BSCL.

Table 2.1

Diagnostic criteria of Berardinelli-Seip Congenital Lipodystrophy (BSCL)

Histological Features

Affected areas of skin show absence of subcutaneous fat.

Investigations

Lab investigations :

Insulin resistance.

Diabetes mellitus between ages 15 and 20 years.

Radiological Investigations :

Hepatomegaly secondary to hepatic steatosis.

Skeletal muscle hypertrophy.

Differential Diagnosis

Leprechaunism (Donohue syndrome ):

Extremely rare, characterized by loss of subcutaneous fat, insulin resistance, growth retardation, and endocrine abnormalities.

Other features that differ from BSCL are large low set ears, widely spread eyes, marked weakness, and early death in the first few months of life.

Lawrence Syndrome :

Represents most of BSCL features, however, occurs only after puberty.

Progeria :

Characteristic facial appearance including prominent eyes, a thin nose with a beaked tip, thin lips, a small chin, and protruding ears.

Other features include alopecia, prominent scalp vein, aged-looking skin, joint abnormalities, sclerotic atrophic limbs and a loss of subcutaneous fat.

Familial partial lipodystrophy :

Occurs in adult.

Features reduced subcutaneous fat in limbs and extremities, with excess subcutaneous fat on face and neck.

Hyperglycemia and hyperlipidemia.

Autoimmune disorders (e.g., SLE and systemic sclerosis) may simulate some features of BSCL.

Loss of subcutaneous fat might be drug induced (HAART treatment of HIV).

Definite Diagnosis

The diagnosis of BSCL is established in a proband with three major criteria or two major criteria plus two or more minor criteria (Table 2.1) and/or by the identification of biallelic pathogenic variants in one of the genes.

Molecular testing approaches can include serial single-gene testing, use of a multi-gene panel, and more comprehensive genomic testing.

Prognosis

Hypertrophic cardiomyopathy is reported in about 20% of individuals and is a significant cause of morbidity from cardiac failure and early mortality around age 30 years.

Other complications of BSCL:

Hyperglycemia (usually insulin resistant with poor response to insulin).

Hyperlipidemia precipitating acute pancreatitis.

Fatty liver resulting in cirrhosis and liver failure.

Bony cysts leading to pathological fractures.

Treatment

No curative treatment is yet established.

Treatments are only based on the symptomatic management of complications.

A strict dietary regimen is primordial (high caloric diet and low-fat diet to correct the hyperlipidemia). Severe hypertriglyceridemia may be controlled with the use of fibric acid derivatives such as fenofibrate.

Metformin controls the glycemic metabolism and contributes to an appetite reduction and improvement of hepatic steatosis and polycystic ovary syndrome. In some cases, insulin may also be necessary for type 2 diabetes.

In the last years, several studies reported the use of recombinant leptin in BSCL. It may correct leptin deficiency, hyperglycemia, and hyperlipidemia.

Liver transplantation might be required in case of liver failure.

Surgery can contribute to correction of facial Lipoatrophy.

Management of This Case

The patient was referred to internal medicine for the management of hyperlipidemia and diabetes.

../images/469075_1_En_2_Chapter/469075_1_En_2_Figa_HTML.jpg Message

Berardinelli–Seip congenital lipodystrophy (BSCL) syndrome is a rare autosomal disease characterized by congenital lipoatrophy with lipid and glycidic metabolism deregulations.

In a case of reduced subcutaneous fact, remember to examine levels of blood sugar and lipids and to check for liver enlargement.

BSCL treatment currently is only symptomatic and does not prevent disease complications.

Leptin treatment in BSCL should be considered an essential promising new curative therapy.

Bibliography

1.

Agarwal A, Simba V, Oral E, et al. Phenotypic and genetic heterogeneity in congenital generalized lipodystrophy. J Clin Endocrinol Metab. 2003;88:4840–7.Crossref

2.

Bennett T, Allford M. Delayed emergence from anesthesia in a child with congenital generalized lipodystrophy (Berardinelli–Seip syndrome). Pediatr Anaesth. 2012;22:299–300.Crossref

3.

Berardinelli W. An undiagnosed endocrine metabolic syndrome: report of 2 cases. J Clin Endocrinol Metab. 1954;14:193–204.Crossref

4.

Ebihara K, Kusakabe T, Hirata M, et al. Efficacy and safety of leptin replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. J Clin Endocrinol Metab. 2007;92:532–41.Crossref

5.

Garg A. Acquired and inherited lipodystrophies. New Engl J Med. 2004;350:1220–34.Crossref

6.

Garg A, Fleckenstein J, Peshock R, et al. Peculiar distribution of adipose tissue in patients with congenital generalized lipodystrophy. J Clin Endocrinol Metab. 1992;75:358–61.PubMed

7.

Garg A, Wilson R, Barnes R, et al. A gene for congenital generalized lipodystrophy maps to human chromosome 9q34. J Clin Endocrinol Metab. 1999;84:3390.Crossref

8.

Gomes K, Pardini V, Ferreira A, et al. Phenotypic heterogeneity in biochemical parameters correlates with mutations in AGPAT2 or Seipin genes among Berardinelli–Seip congenital lipodystrophy patients. J Inherit Metab Dis. 2005;28:1123–31.Crossref

9.

Gomes K, Pardin V, Fernandes A. Clinical and molecular aspects of Berardinelli–Seip congenital lipodystrophy (BSCL). Clin Chim Acta. 2009;402:1–6.Crossref

10.

Khandpur S, Kumar A, Khadgawat R. Congenital generalized lipodystrophy of Berardinelli-Seip type: a rare case. Indian J Dermatol Venereol Leprol. 2011;77:402.Crossref

11.

Magré J, Delépine M, Khallouf E, et al. Identification of the gene altered in Berardinelli–Seip congenital lipodystrophy on chromosome 11q13. Nat Genet. 2001;28:365.Crossref

12.

Oral E, Simha V, Ruiz E, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med. 2002;346:570–8.Crossref

13.

Pagon RA, Bird TD, Dolan CR, et al. Berardinelli–Seip congenital lipodystrophy. Gene Reviews. 2003:1993.

14.

Pardini V, Victória I, Rocha S, et al. Metformin improves metabolic control in subjects with congenital generalized lipoatrophic diabetes. In: 57th Annual Scientific Sessions, Boston, Massachusetts. Diabetes. 1997;46:160A.Crossref

15.

Seip M, Trygstad O. Generalized lipodystrophy. Arch Dis Child. 1963;38:447–53.Crossref

16.

Seip M, Trygstad O. Generalized lipodystrophy, congenital and acquired (lipoatrophy). Acta Paediatr Suppl. 1996;413:2–28.Crossref

17.

Van Maldergem L, Magré J, Khallouf T, et al. Genotype–phenotype relationship in Berardinelli–Seip congenital lipodystrophy. J Med Genet. 2002;39:722–33.Crossref

© Springer Nature Switzerland AG 2019

M. A. El-Darouti, F. M. Al-AliChallenging Cases in Dermatology Volume 2https://doi.org/10.1007/978-3-030-21855-3_3

3. A Congenital Oval Plaque

Mohammad Ali El-Darouti¹  and Faiza Mohamed Al-Ali²

(1)

Faculty of Medicine, Cairo University, Cairo, Egypt

(2)

Dubai Health Authority, Rashid Hospital, Dubai, United Arab Emirates

Keywords

HamartomaCongenitalAtrphic plaqueCD34Factor XIIIASpindle cellsDendritic cells

Clinical Data (Figs. 3.1 and 3.2)

A 1 YO male, presented with a single, atrophic, hyperpigmented plaque on the chest.

The lesion had an oval shape and started to appear since birth.

It was not preceded by any ulceration.

There was no history of trauma.

The baby was otherwise healthy.

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Figs. 3.1 and 3.2

An oval shaped hyperpigmented atrophic plaque on the chest of a baby

Differential Diagnosis

Possible diagnoses for such a clinical presentation include:

Aplasia cutis congenita (ACC):

In ACC the baby is born with an ulcerative lesion.

Also, the lesion of ACC is usually located in the scalp and rarely in other parts of the body.

Anetoderma;

It presents with atrophic plaques

However, lesions of anetoderma are acquired, smaller in size, and usually multiple.

Atrophic morphea;

It presents with atrophic plaques that are ivory hyperpigmented surface.

However, atrophic morphea is acquired and usually multiple.

Medallion- like dermal dendrocyte hamartoma (MLDDH):

It presents with skin-colored or hyperpigmented atrophic plaque.

The lesion of MLDDH presents at birth (congenital).

MLDDH occurs on the trunk and neck.

Congenital atrophic dermatofibrosarcoma protuberans (DFSP):

It presents with skin-colored or hyperpigmented atrophic plaque.

The lesion of congenital DFSP presents at birth (congenital).

It occurs on the trunk and neck.

Accordingly, the most likely clinical differential diagnoses are:

Medallion-like dermal dendrocyte hamartoma (MLDDH).

Congenital atrophic dermatofibrosarcoma protuberans (DFSP) .

Investigations

Lab investigations:

Routine lab tests were within normal ranges.

Radiological investigations:

Not done.

Biopsy Findings (Figs. 3.3, 3.4, 3.5, and 3.6)

Histological features of the lesion included:

Mildly atrophic epidermis.

Interstitial infiltrate of spindle cells with no storiform pattern or atypical features.

Diminished collagen bundles.

Preserved adnexal structures.

Immunohistochemistry result:

S100 PTN: negative.

Vimentin: positive.

CD34: positive.

Factor XIIIa: positive.

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Fig. 3.3

Mildly atrophic epidermis

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Fig. 3.4

Interstitial infiltrate of spindle cells with no storiform pattern or atypical features

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Fig. 3.5

Diminished collagen bundles and preserved adnexal structures

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Fig. 3.6

CD34: positive

Tips

In the discussion of clinical differential diagnosis, the most likely two disorders were:

Medallion- like dermal dendrocyte hamartoma (MLDDH).

Congenital atrophic dermatofibrosarcoma protuberans (DFSP).

Histologically, both these disorders feature interstitial spindle cells in the dermis and CD34: positive.

However, congenital atrophic DFSP has the following features:

Variable mitosis.

Atypical cells.

CD34: positive.

Factor XIIIa: negative

Since the above features did not match the histological findings in the case. The diagnosis of congenital atrophic DFSP was excluded.

This made MLDDH the most likely diagnosis.

Based on the Following Findings

The clinical presentation of a congenital, oval-shaped, atrophic plaque situated on the trunk.

The histopathological features of mildly atrophic epidermis with interstitial dermal spindle cells infiltrate, and absence of mitotic figures and atypical cells.

The immunohistochemical results of CD34 and Factor XIIIa positivity.

Exclusion of other differential diagnoses.

The Final Diagnosis was

Medallion-Like Dermal Dendrocyte Hamartoma (MLDDH)

About the Diagnosis

Definition

Medallion-Like Dermal Dendrocyte Hamartoma (MLDDH) is an extremely rare, recently described CD34-positive spindle-cell tumor.

Clinically, MLDDH presents as a solitary, several centimeter-sized, round or oval, erythematous to yellow-brown, atrophic plaque on the neck or upper trunk.

Microscopically, MLDDH is characterized by a proliferation of CD34 positive spindle-shaped cells mainly in the reticular dermis.

Rodríguez-Jurado et al. first reported MLDDH in 2004.

Epidemiology

Only 13 cases of MLDDH have been reported in the literature.

11 females and 2 males.

Lesions are detected immediately after birth.

Pathogenesis and Etiology

Because the lesions are usually detected at or immediately after birth, they have been classified as hamartomas.

This hamartoma is arising from dermal dendrocytes due to either:

Clonal population of dermal dendrocytes.

Post zygotic mutation leading to cutaneous mosaicism.

Dermal dendrocytes are bone marrow-derived mesenchymal cells divided into two types, with specific features for each type (Table 3.1).

Table 3.1

Types of dermal dendrocytes

Clinical Features

All reported cases presented with the following features::

Congenital (lesions are detected immediately after birth).

Atrophic plaques.

Located in the upper trunk or the neck.

Several centimeter-sized.

Rounded or oval/medallion-like shape.

Erythematous to yellow-brown color.

Histological Features

Histopathologically, MLDDH is characterized by the following features:

Atrophic epidermis.

Interstitial infiltrate of spindle-shaped cells with no storiform pattern or atypical features.

Spindle-shaped cells or ovoid cells are mainly in the reticular dermis and extending into the subcutis in some cases.

Diminished collagen bundles.

Preserved adnexal structures.

Immunohistochemistry:

CD34: positive.

Factor XIIIa: positive.

Investigations

Lab investigations:

Not needed.

Radiological investigations:

Not needed.

Differential Diagnosis

Aplasia cutis congenita (ACC).

Anetoderma.

Atrophic morphea.

Congenital atrophic dermatofibrosarcoma protuberans (DFSP) .

Tips

Few cases of MLDDH which were initially misdiagnosed as congenital atrophic DFSP were reported.

Because MLDDH shares some clinical and histopathological characteristics with congenital atrophic DFSP, the differential diagnosis is difficult.

On the immunohistochemical stain, however, the proliferation of spindle cells in MLDDH is positive for factor XIIIa and fascin as well as for CD34, suggesting a dermal dendritic cell property, whereas congenital atrophic DFSP is negative for factor XIIIa.

In some cases showing ambiguous immunohistochemical results, the fluorescence in situ hybridization (FISH) analysis using two-color probes for COL1A1 and PDGFB genes is a useful tool to differentiate DFSP from ML-DDH, because DFSP displays gene translocation t(17;22)(q22;q13) and chimeric COL1A1-PDGFB mRNA expression.

Nevertheless, the importance of immunochemical stains, such as factor XIIIa and CD34, should not be underestimated in the differential diagnosis between MLDDH and DFSP.

Table 3.2 summarizes the differentiating points between MLDDH and DFSP.

Table 3.2

Summary of the differentiating points between MLDDH and DFSP

Definite Diagnosis

A definite diagnosis of MLDDH is based on the followings:

The clinical presentation of a congenital, round or oval-shaped, atrophic plaque on the trunk.

The histopathological features of atrophic epidermis with interstitial dermal spindle cells infiltrate, and absence of mitotic figures.

The immunohistochemistry of CD34 and Factor XIIIa positivity.

Exclusion of other differential diagnoses.

Prognosis

With complete excision, cases showed no recurrence.

Treatment

Complete excision

Management of This Case

This case was managed by complete excision.

../images/469075_1_En_3_Chapter/469075_1_En_3_Figa_HTML.jpg Message

Medallion-Like Dermal Dendrocyte Hamartoma (MLDDH) is an extremely rare condition with only 13 cases reported in the literature.

Although MLDDH has a characteristic clinical picture biopsy is mandatory to exclude congenital Dermatofibrosarcoma Protuberans (DFSP).

Careful clinicopathological examination, including immunochemical stains such as factor XIIIa and CD34 is essential, particularly when the dermatologist encounters a solitary large congenital atrophic lesson on the neck or upper trunk with histopathology of a dermal proliferation of spindle cells.

Bibliography

1.

Cheon M, Jung KE, Kim HS, Lee JY, Kim H-O, Park CK, Park YM. Medallion-like dermal dendrocyte hamartoma: differential diagnosis with congenital atrophic dermatofibrosarcoma protuberans. Ann Dermatol. 2013;25(3):382–4.Crossref

2.

Ducharme EE, Baribault KE, Husain S, Engler DE. Medallion-like dermal dendrocyte hamartoma in a 36-year-old male. J Am Acad Dermatol. 2008 Jul;59(1):169–72.Crossref

3.

Horikawa H, Sato T, Gomi H, Yamazaki K, Ishida Y, Yuzaki I, Fukuzumi S. Medallion-like dermal dendrocyte hamartoma: a rare congenital CD34-positive dermal lesion clinically and pathologically overlapping with fibroblastic connective tissue nevus. Pediatr Dermatol. 2019; https://​doi.​org/​10.​1111/​pde.​13766.Crossref

4.

Kutzner H, Mentzel T, Palmedo G, Hantschke M, Rutten A, Paredes BE, et al. Plaque-like CD34-positive dermal fibroma (medallion-like dermal dendrocyte hamartoma): clinicopathologic, immunohistochemical, and molecular analysis of 5 cases emphasizing its distinction from superficial, plaque-like dermatofibrosarcoma protuberans. Am J Surg Pathol. 2010;34(2):190–201.Crossref

5.

Maire G, Fraitag S, Galmiche L, Keslair F, Ebran N, Terrier-Lacombe MJ, et al. A clinical, histologic, and molecular study of 9 cases of congenital dermatofibrosarcoma protuberans. Arch Dermatol. 2007;143:203–10.Crossref

6.

Marque M, Bessis D, Pedeutour F, Viseux V, Guillot B, Fraitag-Spinner S. Medallion-like dermal dendrocyte hamartoma: the main diagnostic pitfall is congenital atrophic dermatofibrosarcoma. Br J Dermatol. 2009;160:190–3.Crossref

7.

Martin L, Combemale P, Dupin M, Chouvet B, Kanitakis J, Bouyssou-Gauthier ML, et al. The atrophic variant of dermatofibrosarcoma protuberans in childhood: a report of six cases. Br J Dermatol. 1998 Oct;139(4):719–25.PubMed

8.

Porubsky CF, Combs A, Buckley C, Goodman MB. Hypocellular medallion-like dermal dendrocyte hamartoma on the abdomen of a 25 year old male. J Cutan Pathol. 2019;46(4):297–300.Crossref

9.

Restano L, Fanoni D, Colonna C, Gelmetti C, Berti E. Medallion-like dermal dendrocyte hamartoma: a case misdiagnosed as neurofibroma. Pediatr Dermatol. 2010a;27:638–42.Crossref

10.

Restano L, Fanoni D, Colonna C, Gelmetti C, Berti E. Medallion-like dermal dendrocyte hamartoma: a case misdiagnosed as neurofibroma. Pediatr Dermatol. 2010b;27(6):638–42.Crossref

11.

Rodríguez-Jurado R, Palacios C, Durán-McKinster C, Mercadillo P, Orozco-Covarrubias L, Saez-de-Ocariz Mdel M, et al. Medallion-like dermal dendrocyte hamartoma: a new clinically and histopathologically distinct lesion. J Am Acad Dermatol. 2004;51:359–63.Crossref

12.

Shah KN, Anderson E, Junkins-Hopkins J, James WD. Medallion-like dermal dendrocyte hamartoma. Pediatr Dermatol. 2007;24(6):632–6.Crossref

© Springer Nature Switzerland AG 2019

M. A. El-Darouti, F. M. Al-AliChallenging Cases in Dermatology Volume 2https://doi.org/10.1007/978-3-030-21855-3_4

4. A Newborn with Scalp Defect and Terminal Limbs Anomalies

Mohammad Ali El-Darouti¹  and Faiza Mohamed Al-Ali²

(1)

Faculty of Medicine, Cairo University, Cairo, Egypt

(2)

Dubai Health Authority, Rashid Hospital, Dubai, United Arab Emirates

Keywords

Limbs defectsAplasia cutis congenitaSkin atrophyVascular abnormalitiesCutis marmorataPurpuric plaquesCobblestone appearanceHereditary disorderExtremely rareInternal organ

Clinical Data (Figs. 4.1, 4.2, 4.3, 4.4, and 4.5)

A female newborn presented with the following features:

Aplasia cutis congenita (ACC) of the scalp.

Purpuric plaques affecting large areas of the body.

Cutis marmorata telangiectatica congenita (marked skin atrophy with net-like purple pattern and prominent subcutaneous blood vessels).

Areas of cobblestone appearance.

Malformation of the limbs (absent toes of both limbs).

Her mother denied drug intake during pregnancy.

Prenatal sonography revealed a limb defect.

Parents were 1st-degree cousins.

Family history was negative for similar conditions.

../images/469075_1_En_4_Chapter/469075_1_En_4_Fig1a_HTML.png../images/469075_1_En_4_Chapter/469075_1_En_4_Fig1b_HTML.png

Figs. 4.1, 4.2, 4.3, 4.4, and 4.5

A female newborn with aplasia cutis, purpuric plaques affecting large areas of the body, marked skin atrophy with net-like purple pattern and prominent subcutaneous blood vessels, areas of cobblestone appearance, and absent toes of both limbs

Differential Diagnosis

1.

Generalized aplasia cutis congenita:

Presents with aplasia cutis congenita of the scalp.

No purpuric plaques affecting large areas of the body.

No marked skin atrophy and no prominent subcutaneous blood vessels.

No areas of cobblestone appearance.

No malformation of the limbs.

2.

TORCH syndrome:

Presents with purpuric plaques affecting large areas of the body.

No aplasia cutis congenita of the scalp.

No marked skin atrophy and no prominent subcutaneous blood vessels.

No areas of cobblestone appearance.

No malformation of the limbs.

3.

Focal dermal hypoplasia:

Presents with marked skin atrophy.

No aplasia cutis congenita of the scalp.

No purpuric plaques affecting large areas of the body.

No prominent subcutaneous blood vessels.

No areas of cobblestone appearance.

No malformation of the limbs.

4.

Epidermolysis bullosa:

Presents with skin erosions.

No marked skin atrophy and no prominent subcutaneous blood vessels.

No purpuric plaques affecting large areas of the body.

No areas of cobblestone appearance.

No malformation of the limbs.

5.

Bart syndrome:

Presents localized absence of the skin, blister formation, and nail deformity.

Considered a variant of aplasia cutis congenita with epidermolysis bullosa.

No marked skin atrophy and no prominent subcutaneous blood vessels.

No purpuric plaques affecting large areas of the body.

No areas of cobblestone appearance.

No malformation of the limbs.

Investigations

Lab investigations:

Anti EBV titer: normal.

Anti CMV titer: normal.

Anti HSV titer: normal.

Radiological investigations:

CT scan (head): no bony defects.

Abdominal sonography: no abnormalities.

Echocardiography: no cardiac abnormalities.

Biopsy Findings (Figs. 4.6, 4.7, and 4.8)

1.

Biopsy site-1. From thepurpuric plaques (Fig. 4.6)

Thinned epidermis with an almost total absence of the dermis.

A large network of blood vessels underneath the atrophic dermis.

N.B.: This picture is similar to focal dermal hypoplasia (FDH); however, in FDH there is no vascular network. Therefore this diagnosis was excluded.

2.

Biopsy site-2. From thecobblestone appearing skin (Fig. 4.7)

Normal looking epidermis, dermis and skin appendages.

This picture shows a normal skin; thus these areas were of unaffected skin.

3.

Biopsy site-3. From an area of absent skin on the scalp (Fig. 4.8)

Atrophic epidermis, scarred dermis, with absent adnexal structures.

The features confirmed the diagnosis of aplasia cutis congenital (ACC).

../images/469075_1_En_4_Chapter/469075_1_En_4_Fig2_HTML.png

Fig. 4.6

Biopsy from the purpuric plaques showing thinned epidermis with an almost total absence of the dermis. There is a large network of blood vessels underneath the atrophic dermis

../images/469075_1_En_4_Chapter/469075_1_En_4_Fig3_HTML.png

Fig. 4.7

Biopsy from the cobblestone appearing skin. Normal looking epidermis, dermis and skin appendages

../images/469075_1_En_4_Chapter/469075_1_En_4_Fig4_HTML.png

Fig. 4.8

Biopsy from an area of absent skin on scalp showing features of aplasia cutis congenital (atrophic epidermis, scarred dermis, with absent adnexal structures)

Based on the Following Findings

1.

Aplasia cutis congenita (ACC)of the scalp.

2.

Purpuric plaques affecting large areas of the body.

3.

Cutis marmorata telangiectatica congenita (marked skin atrophy with net-like purple pattern and prominent subcutaneous blood vessels).

4.

Areas of cobblestone appearance.

5.

Malformation of the limbs (absent toes of both limbs).

The Final Diagnosis was

Adams Oliver Syndrome (AOS)

About the Diagnosis

Definition

Adams Oliver Syndrome (AOS) is an extremely rare hereditary disorder characterized by the following features:

Aplasia cutis congenita (ACC) of the scalp that may be associated with skull defects.

Limb defects.

Cutis marmorata.

Abnormalities of blood vessels.

AOS was first described in 1945 by Adams & Oliver.

Epidemiology

Extremely rare disorder (only 150 cases reported).

The estimated incidence of about 1 in 225,000 live births.

No ethnic or geographic restrictions.

Males and females are affected equally.

Pathogenesis and Etiology

Adams Oliver syndrome is caused by genetic mutations in at least six genes: (ARPGAP31, DLL4, DOCK6, EOGT, NOTCH1 or EBPJ gene).

Each of these genes plays a pivotal role in embryonic development:

Failure of protein formation is caused by a mutation in the ARHGAP31 gene.

Failure of limb development is caused by a mutation in ALX4&MSX2 gene.

Failure of blood vessel development is caused by a mutation in the DLL4 gene.

Inheritance pattern can be autosomal dominant or, less commonly, autosomal recessive.

The pathophysiologic mechanism of AOS remains unknown, even though it has been speculated that the typical vascular skin changes may probably indicate a congenital abnormal development of small vessels or abnormal pericyte recruitment to vessels.

It has also been hypothesized that AOS results from the interruption of early embryonic blood supply in subclavian arteries and that the gene predisposing to this interruption is inherited in an autosomal dominant fashion.

Other theories are based on developmental disorders of neural tube closure, amniotic adhesions or intrauterine external compressions.

Clinical Features

The primary features of AOS include:

Aplasia cutis congenita (ACC) of the scalp.

Purpuric plaques affecting large areas of the body.

Cutis marmorata telangiectatica congenita.

Marked skin atrophy.

Prominent subcutaneous blood vessels.

Areas of cobblestone appearance.

Malformation of the limbs. This can include nail abnormalities, a fusion of digits (syndactyly) or short digits (brachydactyly) or missing digits (oligodactyly).

AOS may be associated with a variety of CNS complications such as microcephaly, encephalocele, polymicrogyria, ventriculomegaly, hypoplastic corpus callosum, seizure disorders, developmental delay, and mental retardation.

Cardiopulmonary complications such as valvular defects, stenotic lesions of the left heart, cardiomyopathy, heart block, malformation of pulmonary vessels, and progressive pulmonary hypertension have been reported in AOS patients. Therefore, echocardiography for screening or routine workup is pivotal in the management of these patients.

Histological Features

No specific findings.

Investigations

Radiological investigations (X-ray, CT, MRI) for the skull and limbs.

Echocardiography for screening or routine workup in cases with cardiopulmonary complications.

Neurological tests and EEG for CNS evaluation.

Molecular testing approaches can include serial single-gene testing, use of a multi-gene panel, and more comprehensive genomic testing.

Differential Diagnosis

Syndromic Aplasia Cutis Congenita (ACC):

Scalp-ear-nipple (SEN) syndrome (Finlay-Marks syndrome ). Clinical findings include the followings:

Variable combinations of ACC of the scalp (usually in the vertex or occipital region), hypothelia / athelia, mammary hypoplasia, ear anomalies (either cupped, overfolded, or hypoplastic).

Variable digital anomalies including distal hypoplasia, syndactyly, and camptodactyly.

Occasional hypodontia, renal hypoplasia / malformations or ocular anomalies (colobomata or cataracts).

Normal intellectual development; however, affected sibs in one family presented with severe hypotonia and developmental delay, and a severe autosomal recessive form of the condition was suspected.

Focal dermal hypoplasia(Goltz syndrome):

A multisystem disorder characterized primarily by the involvement of the skin, skeletal system, eyes, and face.

It can feature both cutis aplasia and limb anomalies (syndactyly, polydactyly, camptodactyly or oligodactyly).

A distinguishing feature from AOS is that the dermal hypoplasia usually follows lines of Blaschko.

Other distinguishing features of Goltz syndrome include ectodermal dysplasia, subepidermal deposits of subcutaneous fat, metaphyseal striations, and papillomas of the skin and mucous membranes.

Dominant dystrophic epidermolysis bullosa (DDEB):

Typically, ACC lesions are restricted to the limbs, and the clinical diagnosis is clear from persistent skin fragility and blistering postnatal.

Limb anomalies in DDEB are generally limited to the absence of the nails.

Othercausesof syndromic aplasia cutis congenita (ACC):

Chromosome disorders:

Trisomy 13 (Patau syndrome).

Wolf-Hirschhorn syndrome (4p- syndrome).

Setleis syndrome (focal facial dermal dysplasia 3), with bitemporal or preauricular skin lesions resembling ACC.

Johanson-Blizzard syndrome.

Oculocerebrocutaneous (Delleman) syndrome.

Kabuki syndrome.

Limb-body wall complex.

Knobloch syndrome, with high myopia, neuronal elements in scalp defects, occipital encephalocele.

Various ectodermal dysplasias.

Isolated aplasia cutis congenita (ACC):

Estimated to occur in one in 3000 live births, most often as an isolated, sporadic malformation.

Familial recurrence is rarely observed, and can be caused by a heterozygous pathogenic variant in BMS1, a ribosomal GTPase that recruits Rcl1 to preribosomes and promotes ribosomal subunit maturation.

Hypoproliferation and/or impaired differentiation at a location of rapid growth (the cranium) have been hypothesized as part of the pathogenesis for this condition .

Non-genetic causesof aplasia cutis congenita (ACC):

Birth trauma (e.g., scalp electrode avulsion).

Amniotic bands.

Intrauterine vascular disruption (e.g., secondary to embolism from co-twin loss).

Teratogens (misoprostol, cocaine, methotrexate, angiotensin-converting enzyme inhibitors, methimazole, benzodiazepines, valproic acid).

Terminal Transverse Limb Defect (TTLD)

Amniotic band sequence:

Considering that the concurrence of transverse distal limb anomalies with cutis aplasia is diagnostic of AOS, there is not an immediate differential diagnosis for this particular combination of features with the notable exception of amniotic band sequence, which can present as a complete phenocopy, particularly if bands have not been observed on prenatal ultrasonography or at delivery.

Since constriction rings of the limbs or toes have been described with AOS, this feature does not adequately distinguish these two conditions.

It is somewhat unusual for amniotic bands to cause focal scalp defects; in contrast, defects at the vertex of the scalp are most consistent with AOS (but may occur elsewhere).

Some clinicians do not diagnose amniotic band sequence unless band tissue is physically present or is seen on prenatal ultrasound examination, or the amnion is torn or knotted on placental analysis.

In the absence of physical evidence for amnion disruption, constriction rings may be interpreted as evidence of vascular disruption.

Congenital dyserythropoietic anemia type I:

Toes and fingers show limb reductions with absent or hypoplastic nails, often involving partial syndactyly.

Duplicated metacarpals or metatarsals may be seen.

Other features are mild to moderate macrocytic anemia and evidence of ineffective erythropoiesis on bone marrow aspirates.

Jaundice, early onset gallstone formation , and splenomegaly may also be seen.

CBC with blood smear should be performed in patients with TTLD to assess for the macrocytic anemia of congenital dyserythropoietic anemia.

Congenital dyserythropoietic anemia type I is caused by mutation of CDAN1 or C15ORF41 and is inherited in an autosomal recessive manner.

Poland syndrome:

Key features are unilateral hypoplasia or aplasia of part or all of the pectoralis major, ipsilateral axillary hypohidrosis, and ipsilateral upper limb reduction defects, often with syndactyly.

Hypoglossia-hypodactylia anomaly (Hanhart syndrome ):

Key features are small or absent mandibular structures (variably involving mandible, lower incisors, and tongue) and symmetric or asymmetric limb defects.

Non-genetic causesof TTLD:

Teratogens (e.g., phenytoin, misoprostol, and ergotamine).

Vascular disruption of any cause, including thrombosis, which may be primarily due to fetal thrombophilia or may be secondary to other causes such as embolism from co-twin loss.

Chorionic villus sampling (CVS), mainly when performed before ten weeks gestation .

Definite Diagnosis

The diagnosis of AOS is based on clinical signs and symptoms, patient/family history and imaging.

Major criteria for diagnosis are terminal transverse limb defects, aplasia cutis congenita, and family history of AOS.

Minor criteria include cutis marmorata, congenital heart defects as well as vascular anomaly.

The presence of two major criteria or a combination of one major and one minor criterion are sufficient for diagnosis.

Molecular testing approaches can include serial single-gene testing, use of a multi-gene panel, and more comprehensive genomic testing.

Prognosis

Most cases of AOS are likely to have a normal life span.

Some cases may experience complications of cardiac and skull defects leading to long term disabilities and lethal prognosis.

Treatment

There is no cure for AOS.

Treatment focuses on the control of manifestations:

ACC: care by a pediatric dermatologist or plastic surgeon depending on severity. Goals of non-operative therapy are to prevent infection and promote healing. Large and deep lesions with calvarial involvement require acute care and may eventually also require reconstruction by a neurosurgeon.

Limbs: many AOS limb anomalies are not severe enough to require surgical or prosthetic intervention.

Occupational therapy or physical therapy are used as needed to assist with limb functioning.

Lifestyle modifications such as the use of helmets while playing to protect the skull.

Surveillance and referral for other systemic disorders:

Cardiovascular: echocardiography annually until age three years for signs of pulmonary hypertension.

Neurologic: annual pediatric care, including neurologic examination and ongoing assessment of psychomotor development.

Ocular: annual assessment by a pediatric ophthalmologist until the age of three years for evidence of abnormal retinal vascular development.

Evaluation of relatives at risk: a pre-symptomatic diagnosis to identify as early as possible those who would benefit from initiation of treatment and surveillance for cardiovascular, neurologic, and/or ocular manifestations.

Management of This Case

The patient died a few days after referral to a pediatric intensive care unit.

../images/469075_1_En_4_Chapter/469075_1_En_4_Figa_HTML.jpg Message

Adams-Oliver syndrome (AOS) should be suspected in individuals with Aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLD).

AOS is an extremely rare condition (only 150 cases reported), with variable presentations and outcomes.

Internal organ involvement and intellectual disabilities should be considered in the management of these patients.

Understanding the molecular pathogenesis of this disorder can pave the way for more efficient diagnostic and therapeutic modalities.

Bibliography

1.

Adams FH, Oliver CP. Hereditary deformities in man: due to arrested development. J Hered. 1945;36:3–7.Crossref

2.

Amor DJ, Leventer RJ, Hayllar S, Bankier A. Polymicrogyria associated with scalp and limb defects: variant of Adams-Oliver syndrome. Am J Med Genet. 2000;93:328–34.Crossref

3.

Atasoy HI, Tug E, Yavuz T, Cine N. Unique variant of Adams-Oliver syndrome with dilated cardiomyopathy and heart block. Pediatr Int. 2013;55:508–12.Crossref

4.

Becker R, Kunze J, Horn D, Gasiorek-Wiens A, Entezami M, Rossi R, et al. Autosomal recessive type of Adams-Oliver syndrome: prenatal diagnosis. Ultrasound Obstet Gynecol. 2002;20:506–10.Crossref

5.

Bonafede RP, Beighton P. Autosomal dominant inheritance of scalp defects with ectrodactyly. Am J Med Genet. 1979;3:35–41.Crossref

6.

D’Amico A, Melis D, D’Arco F, Di Paolo N, Carotenuto B, D’Anna G, et al. Adams Oliver syndrome: description of a new phenotype with cerebellar abnormalities in a family. Pol J Radiol. 2013;78:83–7.Crossref

7.

Der Kaloustian VM, Hoyme HE, Hogg H, Entin MA, Guttmacher AE. Possible common pathogenetic mechanisms for Poland sequence and Adams-Oliver syndrome. Am J Med Genet. 1991;38:69–73.Crossref

8.

Fryns JP, Legius E, Demaerel P, van den Berghe H. Congenital scalp defect, distal limb reduction anomalies, right spastic hemiplegia and hypoplasia of the left arteria cerebri media. Further evidence that interruption of early embryonic blood supply may result in Adams-Oliver (plus) syndrome. Clin Genet. 1996;50:505–9.Crossref

9.

Hoyme HE, Jones KL, Van Allen MI, Saunders BS, Benirschke K. Vascular pathogenesis of transverse limb reduction defects. J Pediatr. 1982;101:839–43.Crossref

10.

Kalina MA, Kalina-Faska B, Paprocka J, Jamroz E, Pyrkosz A, Marszal E, et al. Do children with Adams-Oliver syndrome require endocrine follow-up?. New information on the phenotype and management. Clin Genet. 2010;78:227–35.Crossref

11.

Küster W, Lenz W, Kääriäinen H, Majewski F. Congenital scalp defects with distal limb anomalies (Adams-Oliver syndrome): report of ten cases and review of the literature. Am J Med Genet. 1988;31:99–115.Crossref

12.

McGoey RR, Lacassie Y. Adams-Oliver syndrome in siblings with central nervous system findings, epilepsy, and developmental delay: refining the features of a severe autosomal recessive variant. Am J Med Genet A. 2008;146A:488–91.Crossref

13.

Mempel M, Abeck D, Lange I, Strom K, Caliebe A, Beham A, et al. The wide spectrum of clinical expression in Adams-Oliver syndrome: a report of two cases. Br J Dermatol. 1999;140:1157–60.Crossref

14.

Patel MS, Taylor GP, Bharya S, Al-Sanna’a N, Adatia I, Chitayat D, et al. Abnormal pericyte recruitment as a cause for pulmonary hypertension in Adams-Oliver syndrome. Am J Med Genet A. 2004;129A:294–9.Crossref

15.

Rajabian MH, Aghaei S. Adams-Oliver syndrome and isolated aplasia cutis congenita in two siblings. Dermatol Online J. 2006;12:17.PubMed

16.

Sankhyan N, Kaushal RK, Jaswal RS. Adams-Oliver syndrome: a case with complete expression. J Dermatol. 2006;33:435–6.Crossref

17.

Seo JK, Kang JH, Lee HJ, Lee D, Sung HS, Hwang SW, et al. A case of Adams-Oliver syndrome. Ann Dermatol. 2010;22:96–8.Crossref

18.

Stittrich AB, Lehman A, Bodian DL, Ashworth J, Zong Z, Li H, et al. Mutations in NOTCH1 cause Adams-Oliver syndrome. Am J Hum Genet. 2014;95:275–84.Crossref

19.

Swartz EN, Sanatani S, Sandor GG, Schreiber RA. Vascular abnormalities in Adams-Oliver syndrome: cause or effect? Am J Med Genet. 1999;82:49–52.Crossref

20.

Sybert VP. Aplasia cutis congenita: a report of 12 new families and review of the literature. Pediatr Dermatol. 1985;3:1–14.Crossref

21.

Trobs RB, Barenbeg K, Hemminghaus M, et al. Herniation of the brain after conservative treatment of a large congenital skull defect in an infant with Adams-Oliver syndrome. J Pediatr Surg. 2010;45(10):2064–7.Crossref

22.

Verdyck P, Holder-Espinasse M, Hul WV, Wuyts W. Clinical and molecular analysis of nine families with Adams-Oliver syndrome. Eur J Hum Genet. 2003;11:457–63.Crossref

23.

Zapata HH, Sletten LJ, Pierpont ME. Congenital cardiac malformations in Adams-Oliver syndrome. Clin Genet. 1995;47:80–4.Crossref

Part IIPart II

Blistering Disorders

The good physician treats the disease, the great physician treats the patient who has the disease.

William Osler

© Springer Nature Switzerland AG 2019

M. A. El-Darouti, F. M. Al-AliChallenging Cases in Dermatology Volume 2https://doi.org/10.1007/978-3-030-21855-3_5

5. Anhidrosis, Atrophic Skin, Dystrophic Teeth, with Blister Formation

Mohammad Ali El-Darouti¹  and Faiza Mohamed Al-Ali²

(1)

Faculty of Medicine, Cairo University, Cairo, Egypt

(2)

Dubai Health Authority, Rashid Hospital, Dubai, United Arab Emirates

Keywords

GenodermatosisEctodermal dysplasiaSkin fragilityAnhidrosisSparse hairNail dystrophyTeeth abnormalitiesSubepidermal blistersPKP1 geneDesmosomes

Clinical Data (Case-1) (Figs. 5.1, 5.2, 5.3, and 5.4)

A 12 YO boy.

Presented with sparse hair, absent eyebrows and eyelashes, and thin atrophic skin.

The skin